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Sample records for amelogenesis imperfecta due

  1. Amelogenesis imperfecta

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    Aldred Michael

    2007-04-01

    Full Text Available Abstract Amelogenesis imperfecta (AI represents a group of developmental conditions, genomic in origin, which affect the structure and clinical appearance of enamel of all or nearly all the teeth in a more or less equal manner, and which may be associated with morphologic or biochemical changes elsewhere in the body. The prevalence varies from 1:700 to 1:14,000, according to the populations studied. The enamel may be hypoplastic, hypomineralised or both and teeth affected may be discoloured, sensitive or prone to disintegration. AI exists in isolation or associated with other abnormalities in syndromes. It may show autosomal dominant, autosomal recessive, sex-linked and sporadic inheritance patterns. In families with an X-linked form it has been shown that the disorder may result from mutations in the amelogenin gene, AMELX. The enamelin gene, ENAM, is implicated in the pathogenesis of the dominant forms of AI. Autosomal recessive AI has been reported in families with known consanguinity. Diagnosis is based on the family history, pedigree plotting and meticulous clinical observation. Genetic diagnosis is presently only a research tool. The condition presents problems of socialisation, function and discomfort but may be managed by early vigorous intervention, both preventively and restoratively, with treatment continued throughout childhood and into adult life. In infancy, the primary dentition may be protected by the use of preformed metal crowns on posterior teeth. The longer-term care involves either crowns or, more frequently these days, adhesive, plastic restorations.

  2. Esthetic and functional rehabilitation of mutilated dentition and loss of vertical dimension due to amelogenesis imperfecta.

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    Mittal, Shweta; Tewari, Sanjay; Goel, Rajat

    2014-04-01

    Cases of severe attrition are a common finding. Among the congenital anomalies, amelogenesis imperfecta and dentinogenesis imperfecta are important conditions that may cause accelerated wear of teeth. The following case report describes the complete oral rehabilitation of a patient diagnosed with amelogenesis imperfecta. A detailed treatment plan was chalked out which included proper oral hygiene measures, restoration of carious teeth and endodontic treatment followed by foundation restorations of teeth that were crucial for the final prostheses. Patient was given transitional restorations for about 6 weeks with the aim of regaining the lost vertical dimensions. Final rehabilitation was done by fixed dental prostheses.

  3. Genetics Home Reference: amelogenesis imperfecta

    Science.gov (United States)

    ... of Tooth Disorders Orphanet: Amelogenesis imperfecta School of Dentistry, University of North Carolina at Chapel Hill Patient ... of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

  4. AMELOGENESIS IMPERFECTA: A CLINICAL REPORT

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    Veena; Sunanda

    2015-01-01

    AIM: This clinical case report describes the oral rehabilitation of a young adult female patient diagnosed with hypoplastic Amelogenesis imperfecta. SUMMARY : Amelogenesis Imperfecta is a hereditary condition that affects the formation of the enamel mineralization process of both the primary and secondary dentition. It is clinically and genetically heterogeneous grou p of condition that affects both the quantity and quality of the enamel structure resulting...

  5. Rough hypoplastic amelogenesis imperfecta with follicular hyperplasia.

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    Peters, E; Cohen, M; Altini, M

    1992-07-01

    This report documents a unique case of rough hypoplastic amelogenesis imperfecta with apparent anterior oligodontia and multiple anomalies of the associated mesenchymally derived tissues. Multiple unerupted teeth showed hypercementosis, distorted roots with aberrant dentin formation, and marked follicular hyperplasia. The hyperplastic follicles had a complex histopathologic appearance that recapitulated some features of the WHO-type odontogenic fibroma. The features of these teeth, the nature of the associated follicular lesions, and their relationship to the unerupted teeth are discussed.

  6. Amelogenesis imperfecta in the dentition of a wild chimpanzee.

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    Towle, Ian; Irish, Joel D; De Groote, Isabelle

    2018-04-01

    This report describes a case of amelogenesis imperfecta in the dentition of a female chimpanzee. Amelogenesis imperfecta is a group of rare genetic conditions that create severe enamel defects, which, although well researched in humans, has not yet been investigated in wild non-human primates. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Amelogenesis imperfecta and localised aggressive periodontitis: A rare clinical entity

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    Gundannavar, Gayatri; Rosh, Radhika M.; Chandrasekaran, Shoba; Hussain, Ahad M.

    2013-01-01

    This case report presents two female patients whose chief complaint was discoloration of teeth. On careful clinical examination it was found that the patients had features of amelogenesis imperfecta and localised aggressive periodontitis. This article will give an insight of clinical and radiographic features of amelogenesis imperfecta with localised aggressive periodontitis, which is a rare clinical entity.

  8. Amelogenesis Imperfecta Due to a Mutation of the Enamelin Gene: Clinical Case With Genotype-phenotype Correlations

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    Lindemeyer, Rochelle G.; Gibson, Carolyn W.; Wright, Timothy J.

    2010-01-01

    The major protein components of the enamel matrix include the most abundant amelogenin proteins as well as less plentiful proteins such as enamelin and ameloblastin. The enamel defect in amelogenesis imperfecta (AI) generally results in enamel that is too thin (hypoplastic) or too soft (hypocalcification or hypomaturation). Previous reports indicate that mutations in the human enamelin gene (ENAM) cause hypoplastic AI through autosomaldominant inheritance patterns and patients may also exhibit an anterior open bite. Although crown resorption of unerupted teeth occurs more frequently in AI patients, this finding has not been previously associated with known ENAM mutations. The purpose of this article was to report the genotype-phenotype correlations for a 9-year, 11-month-old boy with a homozygous ENAM mutation (c.1258_1259insAG). PMID:20298654

  9. Amelogenesis Imperfecta; Genes, Proteins, and Pathways

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    Claire E. L. Smith

    2017-06-01

    Full Text Available Amelogenesis imperfecta (AI is the name given to a heterogeneous group of conditions characterized by inherited developmental enamel defects. AI enamel is abnormally thin, soft, fragile, pitted and/or badly discolored, with poor function and aesthetics, causing patients problems such as early tooth loss, severe embarrassment, eating difficulties, and pain. It was first described separately from diseases of dentine nearly 80 years ago, but the underlying genetic and mechanistic basis of the condition is only now coming to light. Mutations in the gene AMELX, encoding an extracellular matrix protein secreted by ameloblasts during enamel formation, were first identified as a cause of AI in 1991. Since then, mutations in at least eighteen genes have been shown to cause AI presenting in isolation of other health problems, with many more implicated in syndromic AI. Some of the encoded proteins have well documented roles in amelogenesis, acting as enamel matrix proteins or the proteases that degrade them, cell adhesion molecules or regulators of calcium homeostasis. However, for others, function is less clear and further research is needed to understand the pathways and processes essential for the development of healthy enamel. Here, we review the genes and mutations underlying AI presenting in isolation of other health problems, the proteins they encode and knowledge of their roles in amelogenesis, combining evidence from human phenotypes, inheritance patterns, mouse models, and in vitro studies. An LOVD resource (http://dna2.leeds.ac.uk/LOVD/ containing all published gene mutations for AI presenting in isolation of other health problems is described. We use this resource to identify trends in the genes and mutations reported to cause AI in the 270 families for which molecular diagnoses have been reported by 23rd May 2017. Finally we discuss the potential value of the translation of AI genetics to clinical care with improved patient pathways and

  10. Oral Rehabilitation of a Patient with Amelogenesis Imperfecta

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    Cogulu, Dilsah; Becerik, Sema; Emingil, Gülnur; Hart, P. Suzanne; Hart, Thomas C.

    2014-01-01

    Amelogenesis imperfecta is a hereditary disorder that causes defective enamel development in the primary and permanent teeth. Clinical treatment is important to address the esthetic appearance of affected teeth, reduce dentinal sensitivity, preserve tooth structure, and optimize masticatory function. The purpose of this case report was to describe the diagnosis, treatment planning, and dental rehabilitation of a patient with autosomal recessive amelogenesis imperfecta. The patient was followed for 5 years, and evaluation 3 years after restorations revealed no pathology associated with the rehabilitation. The patient’s esthetic and functional expectations were satisfied. PMID:20108745

  11. Enamel ultrastructure in pigmented hypomaturation amelogenesis imperfecta.

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    Wright, J T; Lord, V; Robinson, C; Shore, R

    1992-10-01

    Hypomaturation amelogenesis imperfecta (AI) is a hereditary condition of enamel that is presumed to result from defects during the maturation stage of enamel development. This study characterized the enamel ultrastructure and enamel crystallite morphology, as well as the distribution of organic material in enamel affected with pigmented hypomaturation AI. Enamel exhibiting autosomal recessive pigmented hypomaturation AI was sectioned or fractured and examined using light microscopy, scanning electron microscopy and transmission electron microscopy. Enamel samples were treated with 30% NaOCl or 8 M urea to remove organic components and determine the effect of deproteinization on crystallite morphology. These were compared with untreated normal enamel samples. The enamel crystallites in hypomaturation AI exhibited considerable variability in size and morphology. Examination of deproteinized tissue indicated that the AI crystallites had a thick coating, presumably of organic or partially mineralized material, which was not visible in normal enamel. The results of this investigation provide further evidence that hypomaturation AI is associated with the retention of organic material that is most probably enamel protein. Enamel protein retention is likely to be involved in the inhibition of normal crystallite growth resulting in the morphological crystallite abnormalities associated with this disorder.

  12. Amelogenesis Imperfecta with Anterior Open Bite: A Rare Case Report

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    Singhal, Ruchi; Pathak, Anuradha; Goenka, Puneet

    2011-01-01

    This clinical report describes the treatment plan for a young patient affected by amelogenesis imperfecta with anterior open bite. The objectives of the treatment were to eliminate tooth sensitivity while enhancing esthetics and restoring masticatory function. Treatment included resin composite laminate veneers on maxillary anterior teeth and stainless steel crowns for posterior teeth.

  13. Amelogenesis Imperfecta: Full Mouth Rehabilitation in Deciduous Dentition

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    Pinky,; Naik, Satyajith; ND, Shashikiran

    2010-01-01

    This clinical report describes the oral rehabilitation of a very young child diagnosed with hypoplastic amelogenesis imperfecta. The specific treatment objectives being adequate patient management, eliminate tooth sensitivity while enhancing esthetics, masticatory function and improved self confidence. The treatment included full mouth rehabilitation with stainless steel crowns on posterior teeth and indirect composite veneers on anterior teeth.

  14. Craniofacial features in amelogenesis imperfecta: a report of two ...

    African Journals Online (AJOL)

    Craniofacial features in amelogenesis imperfecta: a report of two cases. MT Osundwa, ML Chindia, SW Guthua, P Devani, WA Odhiambo. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/ajohs.v1i1.29611 · AJOL African Journals Online.

  15. Characterization of the nanoscratch, microstructure, and composition in hypoplastic amelogenesis imperfecta

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    Ping Qing

    2015-07-01

    Full Text Available Hypoplastic amelogenesis imperfecta is a widespread hereditary disease that causes the loss of enamel. The purpose of this study was to investigate the nanoscratch resistance of hypoplastic amelogenesis imperfecta for providing a reference for restorative treatment. Four unerupted third molars from a patient diagnosed with hypoplastic amelogenesis imperfecta and seven unerupted third molars from normal individuals were compared. Atomic force microscopy and energy-dispersive X-ray spectroscopy were used to observe the microstructure and composition of the teeth (enamel and dentin. The nanoscratch tests of teeth (enamel and dentin were investigated using a nanoscratch tester, scanning electron microscopy, and a stylus profilometer. The results indicated that hypoplastic amelogenesis imperfecta teeth had different microstructures compared to normal teeth. Hypoplastic amelogenesis imperfecta demonstrated a higher composition of organic substance. Meanwhile, the friction coefficient of hypoplastic amelogenesis imperfecta was higher than that of normal teeth, and inferior frictional resistance of hypoplastic amelogenesis imperfecta teeth was observed. The main damaging mechanisms observed in hypoplastic amelogenesis imperfecta under nanoscratch were the combination of delamination, debris, and cracks in enamel with delamination, debris, and plastic deformation in dentin. Our findings suggested that new dental restorative materials should be selected to match the mechanical properties of hypoplastic amelogenesis imperfecta.

  16. Minimally invasive rehabilitation of a patient with amelogenesis imperfecta

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    Büchi, Dominik; Fehmer, Vincent; Sailer, Irena; Wolleb, Karin; Jung, Ronald

    2014-01-01

    This case report describes a minimally invasive step-by-step approach to treat a patient with amelogenesis imperfecta. This is a genetic developmental disorder of the dental enamel, which clinically manifests as white and dark discolorations of the teeth. The clinical examination did not reveal the true depth of the staining. Therefore, a step-wise treatment approach was chosen. The first step consisted of a home bleaching procedure, which led to a slight improvement of the esthetic appearanc...

  17. Distal renal tubular acidosis and amelogenesis imperfecta: A rare association

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    P Ravi

    2013-01-01

    Full Text Available Renal tubular acidosis (RTA is characterized by a normal anion gap with hyperchloremic metabolic acidosis. Primary distal RTA (type I is the most common RTA in children. Childhood presentation of distal RTA includes vomiting, failure to thrive, metabolic acidosis, and hypokalemia. Amelogenesis imperfecta (AI represents a condition where the dental enamel and oral tissues are affected in an equal manner resulting in the hypoplastic or hypopigmented teeth. We report a 10-year-old girl, previously asymptomatic presented with the hypokalemic paralysis and on work-up found out to have type I RTA. The discoloration of teeth and enamel was diagnosed as AI.

  18. Acid-etching effects in hypomineralized amelogenesis imperfecta. A microscopic and microanalytical study.

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    Sánchez-Quevedo, Carmen; Ceballos, Gregorio; Rodríguez, Ismael Angel; García, José Manuel; Alaminos, Miguel

    2006-01-01

    The purpose of this study was to use quantitative x-ray microprobe analysis with scanning electron microscopy to define the morphostructural and calcification patterns in the enamel of teeth with the hypomineralized variant of amelogenesis imperfecta. We compared 5 fragments of permanent human canines from patients with clinically diagnosed hypomineralized amelogenesis imperfecta and 5 normal permanent canines from subjects without amelogenesis imperfecta. All specimens were etched with phosphoric acid for morphological and microanalytical examination. Two types of etching patterns were found; in addition, islets of pattern I were seen within areas of pattern II. Microanalysis detected no significant differences in calcium concentration between specimens with amelogenesis imperfecta and normal control specimens after acid etching. Pattern III was not observed. The changes and their distribution in the enamel structure after 30 s of acid etching are described in teeth with this rare disorder. Although these data seem to coincide with alterations in prism development, no alterations in calcium concentration were found.

  19. Functional and esthetic rehabilitation of a child with amelogenesis imperfecta: a case report.

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    Moura, Carmem Dolores Vilarinho Soares de; Pontes, Alessandra Silva; Lopes, Teresinha Soares Pereira; Moura, Lúcia Fátima Almeida de Deus; Lima, Marina Deus Moura de

    2017-01-01

    Amelogenesis imperfecta (AI) is a tooth disorder characterized by the abnormal development of the enamel in response to mutations in the genes involved in amelogenesis. The objective of this article is to present the clinical case of a child with AI in the primary dentition phase. A 4-year-old boy was presented to a clinic by his mother, who complained that her son's smile esthetics were compromised by "weak and yellow teeth." All the teeth showed yellowish discoloration as well as crumbling or missing enamel. Due to the absence of carious lesions and the presence of normal pulp in the teeth, it was decided to restore the dentition with indirect crowns of ceramic-optimized polymer, also known as ceromer. No preparations were performed on the teeth. For this patient, indirect ceromer restorations presented a good treatment option for the rehabilitation of primary teeth affected by AI.

  20. Amelogenesis imperfecta with distal renal tubular acidosis: A novel syndrome?

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    R A Misgar

    2017-01-01

    Full Text Available Amelogenesis imperfecta (AI is a heterogeneous group of inherited dental enamel defects. It has rarely been reported in association with multiorgan syndromes and metabolic disorders. The metabolic disorders that have been reported in association with AI include hypocalciuria, impaired urinary concentrating ability, and Bartter-like syndrome. In literature, only three cases of AI and distal renal tubular acidosis (dRTA have been described: two cases in adults and a solitary case in the pediatric age group. Here, we report a child with AI presenting with dRTA; to the best of our knowledge, our reported case is the only second such case in pediatric age group. Our case highlights the importance of recognizing the possibility of renal abnormalities in patients with AI as it will affect the long-term prognosis.

  1. Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report

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    Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali [Dept. of Conservative Dentistry and Endodontics, Manubhai Patel Dental College, Maharaja Krishnakumarsinhji Bhavnagar University, Vadodara (India)

    2015-09-15

    Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

  2. Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report

    International Nuclear Information System (INIS)

    Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali

    2015-01-01

    Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management

  3. Minimally invasive rehabilitation of a patient with amelogenesis imperfecta.

    Science.gov (United States)

    Büchi, Dominik; Fehmer, Vincent; Sailer, Irene; Wolleb, Karin; Jung, Ronald

    2014-01-01

    This case report describes a minimally invasive step-by-step approach to treat a patient with amelogenesis imperfecta. This is a genetic developmental disorder of the dental enamel, which clinically manifests as white and dark discolorations of the teeth. The clinical examination did not reveal the true depth of the staining. Therefore, a step-wise treatment approach was chosen. The first step consisted of a home bleaching procedure, which led to a slight improvement of the esthetic appearance, but the stains were still clearly visible. The next step was the application of a microabrasion technique. This led to further improvement, but not to a satisfactory result for this patient who had high esthetic expectations. Thus, the third step was undertaken: it was planned to restore the maxillary incisors and canines with ceramic veneers. The dental technician prepared a wax-up, which served as a basis for a clinical mock-up. After discussing the mock-up and the treatment plan with the patient, crown lengthening was performed on teeth 11 and 23 to improve the pink esthetics. Subsequently, the teeth were prepared in a minimally invasive way and a final impression was taken. Following try-in, the six veneers were inserted with resin cement.

  4. Adenovirus gene transfer to amelogenesis imperfecta ameloblast-like cells.

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    Anton V Borovjagin

    Full Text Available To explore gene therapy strategies for amelogenesis imperfecta (AI, a human ameloblast-like cell population was established from third molars of an AI-affected patient. These cells were characterized by expression of cytokeratin 14, major enamel proteins and alkaline phosphatase staining. Suboptimal transduction of the ameloblast-like cells by an adenovirus type 5 (Ad5 vector was consistent with lower levels of the coxsackie-and-adenovirus receptor (CAR on those cells relative to CAR-positive A549 cells. To overcome CAR -deficiency, we evaluated capsid-modified Ad5 vectors with various genetic capsid modifications including "pK7" and/or "RGD" motif-containing short peptides incorporated in the capsid protein fiber as well as fiber chimera with the Ad serotype 3 (Ad3 fiber "knob" domain. All fiber modifications provided an augmented transduction of AI-ameloblasts, revealed following vector dose normalization in A549 cells with a superior effect (up to 404-fold of pK7/RGD double modification. This robust infectivity enhancement occurred through vector binding to both α(vβ3/α(vβ5 integrins and heparan sulfate proteoglycans (HSPGs highly expressed by AI-ameloblasts as revealed by gene transfer blocking experiments. This work thus not only pioneers establishment of human AI ameloblast-like cell population as a model for in vitro studies but also reveals an optimal infectivity-enhancement strategy for a potential Ad5 vector-mediated gene therapy for AI.

  5. Ceramic Veneers and Direct-Composite Cases of Amelogenesis Imperfecta Rehabilitation.

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    Shibata, S; Taguchi, Cmc; Gondo, R; Stolf, S C; Baratieri, L N

    2016-01-01

    The aim of this article is to present two case reports for the treatment of patients affected with amelogenesis imperfecta. One case was treated with composite resin and the other case with ceramic veneers. Esthetic and functional results were achieved using both treatments, and a review of advantages and disadvantages is presented.

  6. Interdisciplinary management for restoration of function and esthetics in a patient with hereditary amelogenesis imperfecta

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    Sushma Dhiman

    2015-01-01

    Full Text Available Amelogenesis imperfecta (AI is a type of the hereditary disorder which is expressed as a group of conditions causing developmental alterations in the structure of enamel. It is associated with a reduction of oral health-related quality-of-life, has an impact on psychological well-being, and leads to various physiological problems. Children or adults with AI express varying degree of malocclusions either in the form of crowding, impacted teeth, spacing, retained teeth, reduced vertical height due to abnormal tooth structure or undue tooth loss. Orthodontic treatment should precede esthetic rehabilitation. Proper diagnosis of the case is quintessential to provide durable functional and esthetic result to these patients, improving the quality of their lives. We present a case of interdisciplinary management for restoring function and esthetics in a patient with hereditary AI of the hypoplastic type accompanied with tooth impaction and some other dental anomalies.

  7. Multidisciplinary Approach for Restoring Function and Esthetics in a Patient with Amelogenesis Imperfecta: A Clinical Report

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    Kamble, Vaibhav D; Parkhedkar, Rambhau D

    2013-01-01

    Amelogenesis Imperfecta (AI) is a genetically determined and enamel mineralization defect reported, depicted as “Hereditary brown teeth.” AI is characterized as a clinical entity and its clinical manifestations, histological appearance, and genetic pattern are characterized by their heterogeneity. The need for prosthodontic management of this group of patients varies. Some patients need oral hygiene instructions only, whereas others need extensive dental treatment that includes composite rest...

  8. Effect of etching on bonding of a self-etch adhesive to dentine affected by amelogenesis imperfecta.

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    Epasinghe, Don Jeevanie; Yiu, Cynthia Kar Yung

    2018-02-01

    Dentine affected by amelogenesis imperfecta (AI) is histologically altered due to loss of hypoplastic enamel and becomes hypermineralized. In the present study, we examined the effect of additional acid etching on microtensile bond strength of a self-etch adhesive to AI-affected dentine. Flat coronal dentine obtained from extracted AI-affected and non-carious permanent molars were allocated to two groups: (a) Clearfil SE Bond (control); and (b) Clearfil SE Bond and additional etching with 34% phosphoric acid for 15 seconds. The bonded teeth were sectioned into .8-mm 2 beams for microtensile bond strength testing, and stressed to failure under tension. The bond strength data were analyzed using two-way analysis of variance (dentine type and etching step) and Student-Newman-Keuls multiple comparison test (Pself-etch adhesive to AI-affected dentine. © 2017 John Wiley & Sons Australia, Ltd.

  9. Shear bond strength of dentin and deproteinized enamel of amelogenesis imperfecta mouse incisors.

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    Pugach, Megan K; Ozer, Fusun; Mulmadgi, Raj; Li, Yong; Suggs, Cynthia; Wright, J Timothy; Bartlett, John D; Gibson, Carolyn W; Lindemeyer, Rochelle G

    2014-01-01

    The purposes of this study were to: (1) investigate adhesion through shear bond strength (SBS) testing of a resin composite bonded with a self-etching bonding system (SEB) to amelogenesis imperfecta (AI)-affected deproteinized mouse enamel or dentin; and (2) compare wild-type (WT), amelogenin null (AmelxKO), and matrix metalloproteinase-20 null (Mmp20KO) enamel and dentin phenotypes using micro-CT and nanoindentation. Enamel incisor surfaces of WT, AmelxKO, and Mmp20KO mice were treated with SEB with and without sodium hypochlorite and tested for SBS. Incisor dentin was also treated with SEB and tested for SBS. These surfaces were further examined by scanning electron miscroscopy. Micro-CT and nanoindentation analyses were performed on mouse dentin and enamel. Data were analyzed for significance by analysis of variance. Deproteinization did not improve SBS of SEB to these AI-affected enamel surfaces. SBS of AmelxKO teeth was similar in dentin and enamel; however, it was higher in Mmp20KO dentin. The nanohardness of knockout enamel was significantly lower than WT, while knockout dentin nanohardness was not different from WT. Using animal amelogenesis imperfecta models, enamel sodium hypochlorite deproteinization of hypoplastic and hypoplastic-hypomaturation enamel did not increase shear bond strength, while removal of the defective enamel allowed optimal dentin bonding.

  10. Oral rehabilitation of primary dentition affected by amelogenesis imperfecta: a case report.

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    de Souza-e-Silva, Cíntia Maria; Parisotto, Thaís Manzano; Steiner-Oliveira, Carolina; Gavião, Maria Beatriz Duarte; Nobre-Dos-Santos, Marinês

    2010-05-01

    The purpose of the case report was to describe the treatment of a 4(1/2)-year-old boy with amelogenesis imperfect (AI) in the primary dentition. AI is a hereditary condition that affects the development of enamel, causing quantity, structural, and compositional anomalies involving all dentitions. Consequently, the effects can extend to both the primary and secondary dentitions. A 4(1/2)-year-old boy was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of amelogenesis imperfecta. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms of both maxillary and mandibular primary incisors and canines. Improvements in the patient's psychological behavior and the elimination of tooth sensitiveness were observed, and the reestablishment of a normal occlusion resulted in improved eating habits. The child was monitored in the Pediatric Dentistry Clinic at four-month intervals until the mixed dentition stage. The oral rehabilitation of young children with AI is necessary to reestablish the stomatognathic system function, so important for a child's systemic health. An adequate medical history and a careful clinical examination were essential for a correct diagnosis. Treatment was rendered that was appropriate for the child's age and clinical/psychological characteristics. Cost-effective restorative techniques involving stainless steel and composite-resin crowns are shown for the restoration of a young patient with amelogensis imperfecta.

  11. Correction of malocclusion and oral rehabilitation in a case of amelogenesis imperfecta by insertion of dental implants followed by Le Fort I distraction osteogenesis of the edentulous atrophic maxilla

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    Apaydin, Aysegul; Sermet, Bulent; Ureturk, Sevin; Kundakcioglu, Abdulsamet

    2014-01-01

    Background Amelogenesis imperfecta refers a group of hereditary diseases affecting the teeth and can present a variety of clinical forms and appearances, compromising esthetic appearance. Amelogenesis imperfecta variably reduces oral health quality and can result in severe psychological problems. Case presentation We present the management of an amelogenesis imperfecta Angle class III malocclusion case with speech, esthetics and functional problems. This is an example of the rarely presented ...

  12. Satisfaction After Restoring Aesthetics and Function in a Child with Amelogenesis Imperfecta: A Case Report

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    Nihal Özcan

    2016-08-01

    Full Text Available Amelogenesis imperfecta (AI is a hereditary disorder that disrupts the formation of enamel in both primary and permanent dentition. Management of AI is a challenge for the patient and the clinician. This case report presents the management of AI in a six-year-old female patient. Considering the patient’s age, we decided to make removable dentures in order to avoid growth and development problems. Conventional complete dentures were made, vertical dimension was increased, and the desired aesthetics and function were gained. Additionally, satisfaction with prosthodontic rehabilitation was evaluated using a questionnaire. A high level of patient and parent satisfaction was obtained. Treatment planning for patients with AI is related to many factors including the age and socioeconomic status of the patient, the type and severity of the disorder, the intraoral situation at the time the treatment is planned and most importantly, cooperation of the patient plays a major role.

  13. Impact of moderate and severe hypodontia and amelogenesis imperfecta on quality of life and self-esteem of adult patients.

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    Hashem, Atef; Kelly, Alan; O'Connell, Brian; O'Sullivan, Michael

    2013-08-01

    The objective of this study was to investigate the impact of moderate and severe hypodontia and amelogenesis imperfecta on the quality of life and self-esteem of affected adult patients. Forty one adult patients (aged 18-45 years) with clinical and radiological diagnoses of moderate to severe hypodontia and twenty seven patients diagnosed with amelogenesis imperfecta were age and gender matched with a control group of patients attending for routine dental care. Subjects completed the Oral Health Impact Profile [OHIP-49] and Rosenberg Self Esteem Scale. A paired t-test was used to analyse data; the test alpha level was set at P ≤ 0.05. The results for hypodontia patients were significantly different from controls in six out of the seven OHIP-49 domains, the exception being the Handicap domain. Total scores were also significantly different between the two groups (P=0.003). Self-esteem was not significantly different between the two groups (P=0.98). For amelogenesis imperfecta patients the results were significantly different from control patients in four out of the seven domains of the OHIP-49 and also in the total scores (P=0.01). When self-esteem was investigated there was no significant differences between the two groups (P=0.92). Moderate to severe hypodontia and amelogenesis imperfecta have marked negative impacts on the Oral Health Related quality of life of this patient population relative to controls. However, self-esteem was not significantly affected. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta.

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    Wang, Shih-Kai; Choi, Murim; Richardson, Amelia S; Reid, Bryan M; Lin, Brent P; Wang, Susan J; Kim, Jung-Wook; Simmer, James P; Hu, Jan C-C

    2014-04-15

    Integrins are cell-surface adhesion receptors that bind to extracellular matrices (ECM) and mediate cell-ECM interactions. Some integrins are known to play critical roles in dental enamel formation. We recruited two Hispanic families with generalized hypoplastic amelogenesis imperfecta (AI). Analysis of whole-exome sequences identified three integrin beta 6 (ITGB6) mutations responsible for their enamel malformations. The female proband of Family 1 was a compound heterozygote with an ITGB6 transition mutation in Exon 4 (g.4545G > A c.427G > A p.Ala143Thr) and an ITGB6 transversion mutation in Exon 6 (g.27415T > A c.825T > A p.His275Gln). The male proband of Family 2 was homozygous for an ITGB6 transition mutation in Exon 11 (g.73664C > T c.1846C > T p.Arg616*) and hemizygous for a transition mutation in Exon 6 of Nance-Horan Syndrome (NHS Xp22.13; g.355444T > C c.1697T > C p.Met566Thr). These are the first disease-causing ITGB6 mutations to be reported. Immunohistochemistry of mouse mandibular incisors localized ITGB6 to the distal membrane of differentiating ameloblasts and pre-ameloblasts, and then ITGB6 appeared to be internalized by secretory stage ameloblasts. ITGB6 expression was strongest in the maturation stage and its localization was associated with ameloblast modulation. Our findings demonstrate that early and late amelogenesis depend upon cell-matrix interactions. Our approach (from knockout mouse phenotype to human disease) demonstrates the power of mouse reverse genetics in mutational analysis of human genetic disorders and attests to the need for a careful dental phenotyping in large-scale knockout mouse projects.

  15. Novel genetic linkage of rat Sp6 mutation to Amelogenesis imperfecta

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    Muto Taro

    2012-06-01

    Full Text Available Abstract Background Amelogenesis imperfecta (AI is an inherited disorder characterized by abnormal formation of tooth enamel. Although several genes responsible for AI have been reported, not all causative genes for human AI have been identified to date. AMI rat has been reported as an autosomal recessive mutant with hypoplastic AI isolated from a colony of stroke-prone spontaneously hypertensive rat strain, but the causative gene has not yet been clarified. Through a genetic screen, we identified the causative gene of autosomal recessive AI in AMI and analyzed its role in amelogenesis. Methods cDNA sequencing of possible AI-candidate genes so far identified using total RNA of day 6 AMI rat molars identified a novel responsible mutation in specificity protein 6 (Sp6. Genetic linkage analysis was performed between Sp6 and AI phenotype in AMI. To understand a role of SP6 in AI, we generated the transgenic rats harboring Sp6 transgene in AMI (Ami/Ami + Tg. Histological analyses were performed using the thin sections of control rats, AMI, and Ami/Ami + Tg incisors in maxillae, respectively. Results We found the novel genetic linkage between a 2-bp insertional mutation of Sp6 gene and the AI phenotype in AMI rats. The position of mutation was located in the coding region of Sp6, which caused frameshift mutation and disruption of the third zinc finger domain of SP6 with 11 cryptic amino acid residues and a stop codon. Transfection studies showed that the mutant protein can be translated and localized in the nucleus in the same manner as the wild-type SP6 protein. When we introduced the CMV promoter-driven wild-type Sp6 transgene into AMI rats, the SP6 protein was ectopically expressed in the maturation stage of ameloblasts associated with the extended maturation stage and the shortened reduced stage without any other phenotypical changes. Conclusion We propose the addition of Sp6 mutation as a new molecular diagnostic criterion for the

  16. Effect of deproteinization on composite bond strength in hypocalcified amelogenesis imperfecta.

    Science.gov (United States)

    Saroğlu, I; Aras, S; Oztaş, D

    2006-05-01

    The aim of this study was to evaluate the effect of the treatment of sodium hypochlorite (NaOCl) after acid conditioning of the enamel and dentin of the primary teeth affected with hypocalcified amelogenesis imperfecta (HCAI) on the shear bond strength of the composite material. Primary teeth from a 12-year-old girl affected with HCAI and primary teeth collected from apparently healthy children were used. A total of four groups, experimental and control with and without NaOCl treatment were specified. In the control group conventional composite procedure was performed and in the treatment group 5% NaOCl was applied after acid conditioning and then the procedure continued as in the control group. In teeth affected with HCAI, enamel shear bond strengths were significantly enhanced in the treatment group compared with the conventional procedure. Deproteinization could be attributed as effective in enhancing the enamel bonding in HCAI teeth and could be used to overcome the high failure rates of adhesive restorations in HCAI cases.

  17. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

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    Maria Carolina Salomé Marquezin

    2015-01-01

    Full Text Available The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child’s psychosocial development.

  18. Multidisciplinary management of a child with severe open bite and amelogenesis imperfecta.

    Science.gov (United States)

    Millet, Catherine; Duprez, Jean-Pierre

    2013-03-01

    To present a case of multidisciplinary management and fixed rehabilitation of a young girl with amelogenesis imperfecta (AI), a severe open bite and occlusal instability. AI is a genetic disorder characterized by enamel malformations, disturbances in tooth eruption and significant attrition. Early diagnosis is essential, since rapid breakdown of tooth structure may occur, giving rise to acute symptoms and complicated treatment. As AI is frequently accompanied by unesthetic appearance, open bite deformity and malocclusion, a multidisciplinary approach is often required. This clinical report describes the condition and presents the case of a 10-year-old girl with hypocalcified form of AI. Orthodontic treatment and orthognathic surgery were performed as part of the prosthetic treatment plan to achieve acceptable and durable results. They consisted of correcting class II, posterior crossbite and anterior open bite with a fixed orthodontic appliance, Lefort I osteotomy, bilateral mandibular ramus osteotomy and genioplasty. Prosthodontics treatment consisted of metal-ceramic crowns with low-fusing ceramic for good long-term results. No deterioration in the rehabilitation was found after 5 years of follow-up. Complete restoration of severe AI is a long and complex process generally extending over several years. This article shows the important role of interdisciplinary approach to treating a patient with AI over a period of 8 years.

  19. A new locus for autosomal dominant amelogenesis imperfecta on chromosome 8q24.3.

    Science.gov (United States)

    Mendoza, Gustavo; Pemberton, Trevor J; Lee, Kwanghyuk; Scarel-Caminaga, Raquel; Mehrian-Shai, Ruty; Gonzalez-Quevedo, Catalina; Ninis, Vasiliki; Hartiala, Jaana; Allayee, Hooman; Snead, Malcolm L; Leal, Suzanne M; Line, Sergio R P; Patel, Pragna I

    2007-01-01

    Amelogenesis imperfecta (AI) is a collective term used to describe phenotypically diverse forms of defective tooth enamel development. AI has been reported to exhibit a variety of inheritance patterns, and several loci have been identified that are associated with AI. We have performed a genome-wide scan in a large Brazilian family segregating an autosomal dominant form of AI and mapped a novel locus to 8q24.3. A maximum multipoint LOD score of 7.5 was obtained at marker D8S2334 (146,101,309 bp). The disease locus lies in a 1.9 cM (2.1 Mb) region according to the Rutgers Combined Linkage-Physical map, between a VNTR marker (at 143,988,705 bp) and the telomere (146,274,826 bp). Ten candidate genes were identified based on gene ontology and microarray-facilitated gene selection using the expression of murine orthologues in dental tissue, and examined for the presence of a mutation. However, no causative mutation was identified.

  20. Unusual extrinsic staining following microabrasion in a girl with amelogenesis imperfecta.

    Science.gov (United States)

    Rogers, H J; Yesudian, G; Rodd, H D

    2016-08-01

    Developmental defects of enamel (DDE), such as amelogenesis imperfecta (AI), may present with tooth discolouration that is of aesthetic concern to the affected individual. Children and young people with DDE may therefore seek dental interventions to improve their dental appearance. The most commonly employed approaches include microabrasion, bleaching and/or placement of composite resin veneers. A 13-year-old girl with hypomature AI requested treatment for the 'marks' on her teeth which were having a negative impact on her social interactions. Clinical examination revealed generalised dense white opacities, and a microabrasion approach was performed on 11, 12 and 13 using a commercial preparation of 6.6 % hydrochloric acid. Concerningly, the girl's father phoned the next day reporting that his daughter's teeth had turned 'orange'. An urgent review revealed that the treated teeth had indeed become an orange colour. Further enquiry found that the patient had eaten a tomato pizza immediately after her dental treatment and this was believed to have caused the severe extrinsic staining. The patient was provided with a 16 % carbamide peroxide preparation for night-time use in a laboratory-made tray. A 2-week review revealed complete resolution of the staining. Direct composite resin restorations were subsequently provided for the girl's maxillary anterior teeth to achieve an optimal cosmetic result and she has remained pleased with her dental appearance. Clinicians should be aware of the potential for extrinsic staining following microabrasion or tooth bleaching. Patients should be advised against consuming coloured food and drink for at least 48 h after their treatment.

  1. Clinical and molecular analysis of the enamelin gene ENAM in Colombian families with autosomal dominant amelogenesis imperfecta

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    Sandra Gutiérrez

    2012-01-01

    Full Text Available In this study, we analyzed the phenotype, clinical characteristics and presence of mutations in the enamelin gene ENAM in five Colombian families with autosomal dominant amelogenesis imperfecta (ADAI. 22 individuals (15 affected and seven unaffected belonging to five Colombian families with ADAI and eight individuals (three affected and five unaffected belonging to three Colombian families with autosomal recessive amelogenesis imperfecta (ARAI that served as controls for molecular alterations and inheritance patterns were studied. Clinical, radiographic and genetic evaluations were done in all individuals. Eight exons and three intron-exon boundaries were sequenced for mutation analysis. Two of the five families with ADAI had the hypoplasic phenotype, two had the hypocalcified phenotype and one had the hypomaturative phenotype. Anterior open bite and mandibular retrognathism were the most frequent skeletal abnormalities in the families with ADAI. No mutations were found. These findings suggest that ADAI in these Colombian families was unrelated to previously described mutations in the ENAM gene. These results also indicate that other regions not included in this investigation, such as the promoter region, introns and other genes should be considered as potential ADAI candidates.

  2. Interdisciplinary Full Mouth Rehabilitation of a Patient with Amelogenesis Imperfecta: A Case Report with 8 Years Follow-up

    Science.gov (United States)

    Sreedevi, S; Sanjeev, R; Ephraim, Rena; Joseph, Mathai

    2014-01-01

    This case report deals with the interdisciplinary approach of a 28-year-old lady with Amelogenesis imperfecta of the hypoplastic kind. The patient came with a chief illness of worn out teeth, unsatisfactory esthetics and severe sensitivity of teeth. Her family history revealed a related situation in her father’s brother and her sister. On clinical assessment, the crowns of all teeth were worn out. The plan of the treatment was to protect as much tooth structure, restore the vertical dimension, and improve esthetics and masticatory function. The treatment procedures involved prosthodontic, endodontic, and periodontic interventions. After recording the vertical height, endodontic treatment and crown lengthening were performed with respect to the lower anteriors. The lost vertical height was regained in stages by insertion of full coverage crowns for all the teeth. The patient’s esthetic and functional needs were met with systematic and sequential interdisciplinary treatment approach. PMID:25628493

  3. Loss of epithelial FAM20A in mice causes amelogenesis imperfecta, tooth eruption delay and gingival overgrowth.

    Science.gov (United States)

    Li, Li-Li; Liu, Pei-Hong; Xie, Xiao-Hua; Ma, Su; Liu, Chao; Chen, Li; Qin, Chun-Lin

    2016-06-30

    FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam20A-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM20A. By breeding K14-Cre mice with Fam20A(flox/flox) mice, we created K14-Cre;Fam20A(flox/flox) (conditional knock out, cKO) mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography, histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam20A-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice. The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues.

  4. Noninvasive and Multidisciplinary Approach to the Functional and Esthetic Rehabilitation of Amelogenesis Imperfecta: A Pediatric Case Report

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    Juliana Feltrin de Souza

    2014-01-01

    Full Text Available Case Report. An 8-year-old girl with amelogenesis imperfecta (AI reported unsatisfactory aesthetics, difficulty in mastication, and dental hypersensitivity. The intraoral examination observed mixed dentition, malocclusion in anteroposterior relationships, anterior open bite, and dental asymmetry. A hypoplastic form of AI was diagnosed in the permanent dentition. A multidisciplinary planning was performed and divided into preventive, orthopedic, and rehabilitation stages. Initially, preventive treatment was implemented, with fluoride varnish applications, in order to protect the fragile enamel and reduce the dental sensitivity. In the second stage, the patient received an interceptive orthopedic treatment to improve cross-relationship of the arches during six months. Finally, the rehabilitation treatment was executed to establish the vertical dimension. In the posterior teeth, indirect composite resin crowns were performed with minimally invasive dental preparation. Direct composite resin restorations were used to improve the appearance of anterior teeth. Follow-Up. The follow-up was carried out after 3, 6, 12, and 18 months. After 18 months of follow-up, The restoration of integrity, oral hygiene, and patient satisfaction were observed . Conclusion. Successful reduction of the dental hypersensitivity and improvement of the aesthetic and functional aspects as well as quality of life were observed.

  5. Mapping of the locus for autosomal dominant amelogenesis imperfecta (AIH2) to a 4-Mb YAC contig on chromosome 4q11-q21

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    Kaerrman, C.; Holmgren, G.; Forsman, K. [Univ. Hospital, Umea (Sweden)]|[Univ. of Umea (Sweden)] [and others

    1997-01-15

    Amelogenesis imperfecta (Al) is a clinically and genetically heterogeneous group of inherited enamel defects. We recently mapped a locus for autosomal dominant local hypoplastic amelogenesis imperfecta (AIH2) to the long arm of chromosome 4. The disease gene was localized to a 17.6-cM region between the markers D4S392 and D4S395. The albumin gene (ALB), located in the same interval, was a candidate gene for autosomal dominant AI (ADAI) since albumin has a potential role in enamel maturation. Here we describe refined mapping of the AIH2 locus and the construction of marker maps by radiation hybrid mapping and yeast artificial chromosome (YAC)-based sequence tagged site-content mapping. A radiation hybrid map consisting of 11 microsatellite markers in the 5-cM interval between D4S409 and D4S1558 was constructed. Recombinant haplotypes in six Swedish ADAI families suggest that the disease gene is located in the interval between D4S2421 and ALB. ALB is therefore not likely to be the disease-causing gene. Affected members in all six families share the same allele haplotypes, indicating a common ancestral mutation in all families. The AIH2 critical region is less than 4 cM and spans a physical distance of approximately 4 Mb as judged from radiation hybrid maps. A YAC contig over the AIH2 critical region including several potential candidate genes was constructed. 35 refs., 4 figs., 1 tab.

  6. Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a Danish five-generation family with a novel FAM83H nonsense mutation

    DEFF Research Database (Denmark)

    Haubek, Dorte; Gjørup, Hans; Jensen, Lillian Gryesten

    2011-01-01

    BACKGROUND.  Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) is a disease with severe dental manifestations. OBJECTIVES.  The aims were by means of a genome-wide linkage scan to search for the gene underlying the ADHCAI phenotype in a Danish five-generation family and to study...... the phenotypic variation of the enamel in affected family members. RESULTS.  Significant linkage was found to a locus at chromosome 8q24.3 comprising the gene FAM83H identified to be responsible for ADHCAI in other families. Subsequent sequencing of FAM83H in affected family members revealed a novel nonsense...... mutation, p.Y302X. Limited phenotypic variation was found among affected family members with loss of translucency and discoloration of the enamel. Extensive posteruptive loss of enamel was found in all teeth of affected subjects. The tip of the cusps on the premolars and molars and a zone along...

  7. Correction of malocclusion and oral rehabilitation in a case of amelogenesis imperfecta by insertion of dental implants followed by Le Fort I distraction osteogenesis of the edentulous atrophic maxilla.

    Science.gov (United States)

    Apaydin, Aysegul; Sermet, Bulent; Ureturk, Sevin; Kundakcioglu, Abdulsamet

    2014-09-17

    Amelogenesis imperfecta refers a group of hereditary diseases affecting the teeth and can present a variety of clinical forms and appearances, compromising esthetic appearance. Amelogenesis imperfecta variably reduces oral health quality and can result in severe psychological problems. We present the management of an amelogenesis imperfecta Angle class III malocclusion case with speech, esthetics and functional problems. This is an example of the rarely presented delayed eruption with multiple morphologic dental alterations and edentulous maxilla.There are only a few available reports in which this method is used method to correct sagittal discrepancies in edentulous patients.Our treatment plan consisted of a preoperative diagnostic and prosthodontics phase (including preparation of guiding prosthesis), followed by a surgical phase of Le Fort I osteotomy, distraction osteogenesis to correct the malocclusion, implant insertion and a follow up final restorative phase. Our treatment strategy attempts to serve patient needs, achieving function and esthetics while also minimizing the risk of reconstruction failure. Treatment not only restored function and esthetics, but also showed a positive psychological impact and thereby improved perceived quality of life.

  8. Treatment of teeth in the esthetic zone in a patient with amelogenesis imperfecta using composite veneers and the clear matrix technique: A case report

    Directory of Open Access Journals (Sweden)

    Bogosavljević Aleksandar

    2016-01-01

    Full Text Available Introduction. Restorative dental treatment of patients with a generalized form of amelogenesis imperfecta (AI remains a challenge even today. The treatment approach is multidisciplinary and includes action of several dental disciplines such as restorative, orthodontic, and prosthetic dental specialties. Case report. A 18-year-old female patent was referred to the Department of Restorative Dentistry and Periodontology at the Military Medical Academy of Belgrade, Serbia. She was diagnosed with AI and formerly had been treated for a long period of time at the Department of Pediatric Dentistry and Orthodontics. Her primary concern upon arrival was discomfort and concern for the esthetic appearance of the anterior teeth. The treatment was done with the modified clear matrix technique used in composite veneer restoration of teeth in the esthetic zone. Conclusion. Because fixed prosthetic restoration with crowns, is the final treatment of AI patients it involves severe tooth structure loss. The clear matrix method which was done in this case allowed for greater comfort, functionality, simplicity, speed, greater economic efficiency and tooth structure preservation.

  9. Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta

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    Barbara Gasse

    2017-06-01

    Full Text Available Amelogenesis imperfecta (AI designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene (MMP20 produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues, pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI.

  10. Osteogenesis imperfecta due to compound heterozygosity for the LEPRE1 gene.

    Science.gov (United States)

    Moul, Adrienne; Alladin, Amanda; Navarrete, Cristina; Abdenour, George; Rodriguez, Maria M

    2013-10-01

    Osteogenesis imperfecta is a rare connective tissue disorder characterized by bone fragility and low bone density. Most cases are caused by an autosomal dominant mutation in either COL1A1 or COL1A2 gene encoding type I collagen. However, autosomal recessive forms have been identified. We present a patient with severe respiratory distress due to osteogenesis imperfecta simulating type II, born to a non-consanguineous couple with mixed African-American and African-Hispanic ethnicity. Cultured skin fibroblasts demonstrated compound heterozygosity for mutations in the LEPRE1 gene encoding prolyl 3-hydroxylase 1 confirming the diagnosis of autosomal recessive osteogenesis imperfecta type VIII, perinatal lethal type.

  11. Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation.

    Science.gov (United States)

    Marini, Joan C; Reich, Adi; Smith, Simone M

    2014-08-01

    Osteogenesis imperfecta or 'brittle bone disease' has mainly been considered a bone disorder caused by collagen mutations. Within the last decade, however, a surge of genetic discoveries has created a new paradigm for osteogenesis imperfecta as a collagen-related disorder, where most cases are due to autosomal dominant type I collagen defects, while rare, mostly recessive, forms are due to defects in genes whose protein products interact with collagen protein. This review is both timely and relevant in outlining the genesis, development, and future of this paradigm shift in the understanding of osteogenesis imperfecta. Bone-restricted interferon-induced transmembrane (IFITM)-like protein (BRIL) and pigment epithelium-derived factor (PEDF) defects cause types V and VI osteogenesis imperfecta via defective bone mineralization, while defects in cartilage-associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1), and cyclophilin B (CYPB) cause types VII-IX osteogenesis imperfecta via defective collagen post-translational modification. Heat shock protein 47 (HSP47) and FK506-binding protein-65 (FKBP65) defects cause types X and XI osteogenesis imperfecta via aberrant collagen crosslinking, folding, and chaperoning, while defects in SP7 transcription factor, wingless-type MMTV integration site family member 1 (WNT1), trimeric intracellular cation channel type b (TRIC-B), and old astrocyte specifically induced substance (OASIS) disrupt osteoblast development. Finally, absence of the type I collagen C-propeptidase bone morphogenetic protein 1 (BMP1) causes type XII osteogenesis imperfecta due to altered collagen maturation/processing. Identification of these multiple causative defects has provided crucial information for accurate genetic counseling, inspired a recently proposed functional grouping of osteogenesis imperfecta types by shared mechanism to simplify current nosology, and has prodded investigations into common pathways in osteogenesis imperfecta. Such

  12. A Functional Study of Mutations in K+-dependent Na+-Ca2+ Exchangers Associated with Amelogenesis Imperfecta and Non-syndromic Oculocutaneous Albinism.

    Science.gov (United States)

    Jalloul, Ali H; Rogasevskaia, Tatiana P; Szerencsei, Robert T; Schnetkamp, Paul P M

    2016-06-17

    K(+)-dependent Na(+)/Ca(2+) exchangers belong to the solute carrier 24 (SLC24A1-5) gene family of membrane transporters. Five different gene products (NCKX1-5) have been identified in humans, which play key roles in biological processes including vision, olfaction, and skin pigmentation. NCKXs are bi-directional membrane transporters that transport 1 Ca(2+)+K(+) ions in exchange for 4 Na(+) ions. Recent studies have linked mutations in the SLC24A4 (NCKX4) and SLC24A5 (NCKX5) genes to amylogenesis imperfecta (AI) and non-syndromic oculocutaneous albinism (OCA6), respectively. Here, we introduced mutations found in patients with AI and OCA6 into human SLC24A4 (NCKX4) cDNA leading to single residue substitutions in the mutant NCKX4 proteins. We measured NCKX-mediated Ca(2+) transport activity of WT and mutant NCKX4 proteins expressed in HEK293 cells. Three mutant NCKX4 cDNAs represent mutations found in the SCL24A4 gene and three represent mutations found in the SCL24A5 gene involving residues conserved between NCKX4 and NCKX5. Five mutant proteins had no observable NCKX activity, whereas one mutation resulted in a 78% reduction in transport activity. Total protein expression and trafficking to the plasma membrane (the latter with one exception) were not affected in the HEK293 cell expression system. We also analyzed two mutations in a Drosophila NCKX gene that have been reported to result in an increased susceptibility for seizures, and found that both resulted in mutant proteins with significantly reduced but observable NCKX activity. The data presented here support the genetic analyses that mutations in SLC24A4 and SLC24A5 are responsible for the phenotypic defects observed in human patients. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Amelogenesis Imperfect, Enamel Hypoplasia and Fluorosis Dental - Literature Review

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    Flávia Magnani Bevilacqua

    2015-12-01

    Full Text Available The developmental disorders of enamel are abnormalities of structure which can affect both dentitions. These abnormalities include amelogenesis imperfecta, enamel hypoplasia and dental fluorosis. The amelogenesis imperfecta is a hereditary change and enamel hypoplasia is a quantitative defect of enamel that occurs as a result of systemic problems, local and also inherited factors, or even the combination of them. Dental fluorosis is a hypoplasia caused by the chronic ingestion of fluoride during odontogenesis. All these anomalies have similar clinical characteristics, and it is necessary to be careful in their assessment. It is extremely important to know these abnormalities to establish a differential diagnosis and, consequently, a treatment plan, which can be set for each situation. Therefore, the purpose of this study was to review the literature regarding these three anomalies: amelogenesis imperfecta, enamel hypoplasia and dental fluorosis. It was concluded that to establish the differential diagnosis of these abnormalities as well as a proper treatment plan, it is indispensable the professional knowledge associated with the clinical examination. The examination has to consist of medical history and physical examination, and in some cases, x-ray examination.

  14. Scanning Еlectron Мicroscopy of Еnamel and Dentin of Тeeth with Hypocalcified Аmelogenesis Imperfecta

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    Belcheva Ani B.

    2016-03-01

    Full Text Available The histological features of teeth with hypocalcified amelogenesis imperfecta (AI have been poorly studied, which calls into question the effectiveness of modern adhesive techniques used in the treatment of these noncarious defects.

  15. Osteogenesis imperfecta

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    Justin Easow Sam

    2017-01-01

    Full Text Available Osteogenesis imperfecta is a common heritable connective tissue disorder. Nearly ninety percent are due to Type I collagen mutations. Type I-IV are autosomal dominant, and Type VI–XIII are autosomal recessive. They are Graded 1-5 based on severity. Genomic testing is done by collagen analysis from fibroblasts. The mainstay of treatment is bisphosphonate therapy. The prognosis is variable.

  16. Osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Gupte Tejashri

    2006-05-01

    Full Text Available Osteogenesis imperfecta is an inherited disorder of the connective tissue. The extreme bone fragility seen in patients suffering from osteogenesis imperfecta pose a series of problems with regard to behavior management and rendering of quality dental treatment. Presented here a case of a four year old child suffering from osteogenesis imperfecta.

  17. Osteogensis imperfecta type I is commonly due to a COLIAI null allel of type I collagen

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    Willing, M.C.; Pruchno, C.J. (Univ. of Iowa, Iowa City, IA (United States)); Atkinson, M.; Byers, P.H. (Univ. of Washington, Seattle, WA (United States))

    1992-09-01

    Dermal fibroblasts from most individuals with osteogenesis imperfecta (OI) type I produce about half the normal amount of type I procollagen, as a result of decreased synthesis of one of its constituent chains, pro[alpha](I). To test the hypothesis that decreased synthesis of pro[alpha](I) chains results from mutations in the COL1A1 gene, the authors used primer extension with nucleotide-specific chain termination to measure the contribution of individual COL1A1 alleles to the mRNA pool in fibroblasts from affected individuals. A polymorphic Mn/I restriction endonuclease site in the 3'-untranslated region of COL1A1 was used to distinguish the transcripts of the two alleles in heterozygous individuals. Twenty-three individuals from 21 unrelated families were studied. In each case there was marked diminution in steady-state mRNA levels from one COL1A2 allele. Loss of an allele through deletion or rearrangement was not the cause of the diminished COL1A1 mRNA levels. Primer extension with nucleotide-specific chain termination allows identification of the mutant COL1A1 allele in cell strains that are heterozygous for an expressed polymorphism. It is applicable to sporadic cases, to small families, and to large families in whom key individuals are uninformative at the polymorphic sites used in linkage analysis, making it a useful adjunct to the biochemical screening of collagenous proteins for OI. 40 refs., 3 figs., 1 tab.

  18. Osteogenesis Imperfecta due to Mutations in Non-Collagenous Genes-Lessons in the Biology of Bone Formation

    Science.gov (United States)

    Marini, Joan C.; Reich, Adi; Smith, Simone M.

    2014-01-01

    Purpose of Review Osteogenesis imperfecta (OI), or “brittle bone disease”, has mainly been considered a bone disorder caused by collagen mutations. Within the last decade, however, a surge of genetic discoveries has created a new paradigm for OI as a collagen-related disorder, where autosomal dominant type I collagen defects cause most cases, while rare, mostly recessive forms are due to defects in genes whose protein products interact with collagen protein. This review is both timely and relevant in outlining the genesis, development and future of this paradigm shift in the understanding of OI. Recent Findings BRIL and PEDF defects cause types V and VI OI via defective bone mineralization, while defects in CRTAP, P3H1 and CyPB cause types VII-IX via defective collagen post-translational modification. Hsp47 and FKBP65 defects cause types X and XI OI via aberrant collagen crosslinking, folding and chaperoning, while defects in SP7, WNT1, TRIC-B and OASIS disrupt osteoblast development. Finally, absence of the type I collagen C-propeptidase BMP1 causes type XII OI due to altered collagen maturation/processing. Summary Identification of these multiple causative defects has provided crucial information for accurate genetic counseling, inspired a recently proposed functional grouping of OI types by shared mechanism to simplify current nosology, and should prod investigations into common pathways in OI. Such investigations could yield critical information on cellular and bone tissue mechanisms and translate to new mechanistic insight into clinical therapies for patients. PMID:25007323

  19. Epileptic encephalopathy and amelogenesis imperfecta: Kohlschutter-Tonz syndrome

    NARCIS (Netherlands)

    Schossig, A.; Wolf, N.I.; Kapferer, I.; Kohlschutter, A.; Zschocke, J.

    2012-01-01

    Kohlschütter-Tönz syndrome is a rare genetic disorder with epilepsy, psychomotor regression, and a severe enamel defect with yellow or brownish discoloration of the teeth. The first affected family was described in 1974, and 25 patients in 11 families have been reported until now. Inheritance is

  20. Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia

    Directory of Open Access Journals (Sweden)

    MacKie Iain

    2008-11-01

    Full Text Available Abstract The hereditary dentine disorders, dentinogenesis imperfecta (DGI and dentine dysplasia (DD, comprise a group of autosomal dominant genetic conditions characterised by abnormal dentine structure affecting either the primary or both the primary and secondary dentitions. DGI is reported to have an incidence of 1 in 6,000 to 1 in 8,000, whereas that of DD type 1 is 1 in 100,000. Clinically, the teeth are discoloured and show structural defects such as bulbous crowns and small pulp chambers radiographically. The underlying defect of mineralisation often results in shearing of the overlying enamel leaving exposed weakened dentine which is prone to wear. Currently, three sub-types of DGI and two sub-types of DD are recognised but this categorisation may change when other causative mutations are found. DGI type I is inherited with osteogenesis imperfecta and recent genetic studies have shown that mutations in the genes encoding collagen type 1, COL1A1 and COL1A2, underlie this condition. All other forms of DGI and DD, except DD-1, appear to result from mutations in the gene encoding dentine sialophosphoprotein (DSPP, suggesting that these conditions are allelic. Diagnosis is based on family history, pedigree construction and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Differential diagnoses include hypocalcified forms of amelogenesis imperfecta, congenital erythropoietic porphyria, conditions leading to early tooth loss (Kostmann's disease, cyclic neutropenia, Chediak-Hegashi syndrome, histiocytosis X, Papillon-Lefevre syndrome, permanent teeth discolouration due to tetracyclines, Vitamin D-dependent and vitamin D-resistant rickets. Treatment involves removal of sources of infection or pain, improvement of aesthetics and protection of the posterior teeth from wear. Beginning in infancy, treatment usually continues into adulthood with a

  1. Osteogenesis imperfecta.

    Science.gov (United States)

    Brusin, Joyce Helena

    2008-01-01

    "Fragile bones" have been described in medical literature for centuries. Cases dating from antiquity include dental and skeletal details eerily similar to those found among modern patients whose bones fracture easily and whose bodies show signs of muscular and other weakness. Osteogenesis imperfecta--whose name implies "imperfect birth of bone"--is one of these inherited fragile bone syndromes. A generalized disorder of the body's connective tissues, it is most obvious in its effect on bone, but also involves the body's ligaments, tendons, fascia, eyes, skin, teeth and ears. Radiographs, bone scans and other imaging tools are essential in the initial diagnosis, assessment of fracture risk, and planning and tracking of treatment.

  2. Osteogenesis Imperfecta Issues: Constipation

    Science.gov (United States)

    ... Constipation is a problem for some people with osteogenesis imperfecta. Constipation is defined as a decrease in frequency ... to a more serious problem called rectal prolapse. Osteogenesis Imperfecta Foundation • 804 W. Diamond Ave, Suite 210 • Gaithersburg, ...

  3. Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect.

    Science.gov (United States)

    Webb, Emma A; Balasubramanian, Meena; Fratzl-Zelman, Nadja; Cabral, Wayne A; Titheradge, Hannah; Alsaedi, Atif; Saraff, Vrinda; Vogt, Julie; Cole, Trevor; Stewart, Susan; Crabtree, Nicola J; Sargent, Brandi M; Gamsjaeger, Sonja; Paschalis, Eleftherios P; Roschger, Paul; Klaushofer, Klaus; Shaw, Nick J; Marini, Joan C; Högler, Wolfgang

    2017-06-01

    Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI) by dysregulating intracellular calcium flux. Clinical and bone material phenotype description and osteoblast differentiation studies. Natural history study in pediatric research centers. Eight patients with type XIV OI. Clinical examinations included bone mineral density, radiographs, echocardiography, and muscle biopsy. Bone biopsy samples (n = 3) were analyzed using histomorphometry, quantitative backscattered electron microscopy, and Raman microspectroscopy. Cellular differentiation studies were performed on proband and control osteoblasts and normal murine osteoclasts. Type XIV OI clinical phenotype ranges from asymptomatic to severe. Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara, and extraskeletal features (muscular hypotonia, cardiac abnormalities). Proband lumbar spine bone density z score was reduced [median -3.3 (range -4.77 to +0.1; n = 7)] and increased by +1.7 (1.17 to 3.0; n = 3) following bisphosphonate therapy. TMEM38B mutant bone has reduced trabecular bone volume, osteoblast, and particularly osteoclast numbers, with >80% reduction in bone resorption. Bone matrix mineralization is normal and nanoporosity low. We demonstrate a complex osteoblast differentiation defect with decreased expression of early markers and increased expression of late and mineralization-related markers. Predominance of trimeric intracellular cation channel type B over type A expression in murine osteoclasts supports an intrinsic osteoclast defect underlying low bone turnover. OI type XIV has a bone histology, matrix mineralization, and osteoblast differentiation pattern that is distinct from OI with collagen defects. Probands are responsive to bisphosphonates and some show muscular and cardiovascular features possibly related to intracellular calcium flux abnormalities. Copyright © 2017 Endocrine Society

  4. The co-existence of primary hyperparathyroidism and osteogenesis imperfecta.

    Science.gov (United States)

    Salti, I S; Nassar, V H; Bulos, S

    1973-04-07

    A 47-year-old patient suffering from osteogenesis imperfecta was found to have mild hypercalcemia. The latter proved to be due to a parathyroid adenoma. The clinical and laboratory features of this association are summarized, and the implications of serum calcium abnormalities in osteogenesis imperfecta are discussed.

  5. CLINICAL CASE OF RARE TYPE V OSTEOGENESIS IMPERFECTA

    Directory of Open Access Journals (Sweden)

    G. T. Yakhyayeva

    2015-01-01

    Full Text Available Osteogenesis imperfecta, also known as the brittle bone disease, is a clinically heterogenic hereditary connective tissue disease characterized by brittle bones and high risk of skeletal bone fractures. Other observable symptoms, such as deformities of limb and spinal bones, blue sclerae, dentinogenesis imperfecta and progressive hearing loss vary in severity depending on the type of the disease. According to the original classification by D.O. Silence (1979, there are 4 types of osteogenesis imperfecta; however, the number thereof has multiplied due to discovery of new disease-inducing mutations. Type V osteogenesis imperfecta is distinguished by characteristic clinical radiographic symptoms; also, patients with this type of the disease do not feature a type I collagen gene mutation. Nevertheless, all types of osteogenesis imperfecta, including type V, are characterized by high bone brittleness, frequent fractures and further bone deformities, which is the most common cause of incapacitation of the patients.

  6. Osteogenesis Imperfecta Foundation

    Science.gov (United States)

    ... verified information to families and healthcare professionals, funds new OI research and promotes public policy that supports people living ... in Baltimore, Maryland! Watch the OI Foundation’s PSA Breakthrough ... Opportunities © Osteogenesis Imperfecta Foundation, ...

  7. Learning about Osteogenesis Imperfecta

    Science.gov (United States)

    Skip to main content Learning About Osteogenesis Imperfecta Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research ...

  8. Osteogenesis imperfecta/lobstein syndrome associated with dentinogenesis imperfecta.

    Science.gov (United States)

    Lingaraju, Naresh; Nagarathna, P J; Vijayalakshmi, R; Sheshadri, P

    2013-01-01

    Osteogenesis imperfecta is a collagen related disorder characterized by increased bone fragility and low bone mass. The important oral finding in osteogenesis imperfect is the presence of dentinogenesis imperfecta. This article presents a case of osteogenesis imperfecta (type IV B) with dentinogenesis imperfecta where a 7-year-old girl had opalacent primary teeth associated with severe bone deformity, scoliosis, barrel shaped rib cage, and short stature. The clinical, radiographic ad histologic features are reviewed along with management aspects.

  9. Cardiovascular disease in patients with osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Gram, Jeppe

    2016-01-01

    BACKGROUND: Osteogenesis imperfecta (OI) is a hereditary connective tissue disease often due to mutations in genes coding for type 1 collagen. Collagen type 1 is important in the development of the heart and vasculature. Little is known about the risk of cardiovascular disease (CVD) in OI...

  10. Dentinogenesis imperfecta associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Mina Biria

    2012-01-01

    Full Text Available This paper presents a case with dentinogenesis imperfecta (DI associated with osteogenesis imperfecta. Systemic and dental manifestations of OI and its medical and dental treatments are discussed in this paper. A 5-year-old child with the diagnosis of OI was referred to the Dental School of Shaid Beheshti University of Medical Sciences. On clinical examination yellow/brown discoloration of primary teeth with the attrition of the exposed dentin and class III malocclusion was observed. Enamel of first permanent molars was hypoplastic. Radiographic examinations confirmed the diagnosis of DI. A histological study was performed on one of the exfoliating teeth, which showed abnormal dentin. Primary teeth with DI were more severely affected compared to permanent teeth; enamel disintegration occurred in teeth with DI, demonstrating the need for restricts recalls for these patients.

  11. Osteogenesis imperfecta type V

    DEFF Research Database (Denmark)

    Rauch, Frank; Moffatt, Pierre; Cheung, Moira

    2013-01-01

    Osteogenesis imperfecta (OI) type V is an autosomal dominant bone fragility disorder that we had described a decade ago. Recent research has shown that OI type V is caused by a recurrent c.-14C>T mutation in IFITM5. In the present study, we assessed all patients diagnosed with OI type V at our...

  12. Dentinogenesis imperfecta: A case report

    Directory of Open Access Journals (Sweden)

    Subramaniam P

    2008-06-01

    Full Text Available Dentinogenesis imperfecta is an autosomal dominant disorder of tooth development characterized by the presence of opalescent dentin, resulting in a dusky blue to brownish discoloration of the teeth. This condition is genetically and clinically heterogeneous; it may affect only the teeth or it may be associated with the osteogenesis imperfecta. Dentinogenesis imperfecta has been subdivided into three types: type I is associated with osteogenesis imperfecta; in type II there is no associated osteogenesis imperfecta; and when the condition is associated with the Brandywine triracial isolate and large pulp chambers it is classified as type III. This report describes a 16-year-old female patient who showed the characteristic dental features of dentinogenesis imperfecta type II. The etiology and prevalence of the disorder, and a comprehensive treatment plan, will be briefly reviewed.

  13. Defective Proteolytic Processing of Fibrillar Procollagens and Prodecorin Due to Biallelic BMP1 Mutations Results in a Severe, Progressive Form of Osteogenesis Imperfecta.

    Science.gov (United States)

    Syx, Delfien; Guillemyn, Brecht; Symoens, Sofie; Sousa, Ana Berta; Medeira, Ana; Whiteford, Margo; Hermanns-Lê, Trinh; Coucke, Paul J; De Paepe, Anne; Malfait, Fransiska

    2015-08-01

    Whereas the vast majority of osteogenesis imperfecta (OI) is caused by autosomal dominant defects in the genes encoding type I procollagen, mutations in a myriad of genes affecting type I procollagen biosynthesis or bone formation and homeostasis have now been associated with rare autosomal recessive OI forms. Recently, homozygous or compound heterozygous mutations in BMP1, encoding the metalloproteases bone morphogenetic protein-1 (BMP1) and its longer isoform mammalian Tolloid (mTLD), were identified in 5 children with a severe autosomal recessive form of OI and in 4 individuals with mild to moderate bone fragility. BMP1/mTLD functions as the procollagen carboxy-(C)-proteinase for types I to III procollagen but was also suggested to participate in amino-(N)-propeptide cleavage of types V and XI procollagens and in proteolytic trimming of other extracellular matrix (ECM) substrates. We report the phenotypic characteristics and natural history of 4 adults with severe, progressive OI characterized by numerous fractures, short stature with rhizomelic shortening, and deformity of the limbs and variable kyphoscoliosis, in whom we identified novel biallelic missense and frameshift mutations in BMP1. We show that BMP1/mTLD-deficiency in humans not only results in delayed cleavage of the type I procollagen C-propeptide but also hampers the processing of the small leucine-rich proteoglycan prodecorin, a regulator of collagen fibrillogenesis. Immunofluorescent staining of types I and V collagen and transmission electron microscopy of the dermis show impaired assembly of heterotypic type I/V collagen fibrils in the ECM. Our study thus highlights the severe and progressive nature of BMP1-associated OI in adults and broadens insights into the functional consequences of BMP1/mTLD-deficiency on ECM organization. © 2015 American Society for Bone and Mineral Research.

  14. A rare combination of amniotic constriction band with osteogenesis imperfecta.

    Science.gov (United States)

    Shah, Krupa Hitesh; Shah, Hitesh

    2015-11-11

    Amniotic constriction bands and osteogenesis imperfecta are disorders arising from a collagen defect. We report a rare association of amniotic bands with osteogenesis imperfecta in a child. The child was born with multiple amniotic bands involving the right leg, both hands and both feet. Multiple fractures of long bones of lower limbs occurred in childhood due to trivial trauma. Deformities of the femur and tibia due to malunion with osteopenia and blue sclerae were present. The patient was treated with z plasty of constriction band of the right tibia and bisphosphonate for osteogenesis imperfecta. This rare association of both collagen diseases may provide further insight for the pathogenesis of these diseases. 2015 BMJ Publishing Group Ltd.

  15. Child Abuse or Osteogenesis Imperfecta?

    Science.gov (United States)

    Child Abuse or Osteogenesis Imperfecta? A child is brought into the emergency room with a fractured leg. The ... welfare services to report a suspected case of child abuse. The child is taken away from the parents ...

  16. Genetics Home Reference: dentinogenesis imperfecta

    Science.gov (United States)

    ... 2 Orphanet: Dentinogenesis imperfecta type 3 School of Dentistry, University of North Carolina at Chapel Hill Patient ... of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

  17. Genetics Home Reference: osteogenesis imperfecta

    Science.gov (United States)

    ... two extremes. Increasingly, genetic factors are used to define the different forms of osteogenesis imperfecta . The milder ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

  18. Osteogenesis imperfecta in childhood: treatment strategies

    NARCIS (Netherlands)

    Engelbert, R. H.; Pruijs, H. E.; Beemer, F. A.; Helders, P. J.

    1998-01-01

    Osteogenesis imperfecta (OI) is a skeletal disorder of remarkable clinical variability characterized by bone fragility, osteopenia, variable degrees of short stature, and progressive skeletal deformities. Additional clinical manifestations such as blue sclerae, dentinogenesis imperfecta, joint

  19. Orthotic treatment of positional brachycephaly associated with osteogenesis imperfecta.

    Science.gov (United States)

    Matarazzo, Carolina G; Schreen, Gerd; Lago-Rizzardi, Camilla D do; Peccin, Maria Stella; Pinto, Fernando Cg

    2017-12-01

    Osteogenesis imperfecta is an inherited disorder of the connective tissue characterized primarily by fractures with no or small causal antecedents and extremely variable clinical presentation. The disorder requires a global and, therefore, multidisciplinary therapeutic approach that should aim, among other aspects, at the prevention and treatment of deformities resulting from osteogenesis imperfecta. Due to limitations related to bony deformities, it can be difficult to place these infants in a variety of positions that would help remediate skull deformities, so a cranial orthosis becomes the therapy of choice. The aim of this study was to demonstrate the results obtained during treatment with a cranial remolding orthosis (helmet) in babies with osteogenesis imperfecta. Case Description and Methods: For the first time in the scientific literature, this study describes the use of a cranial orthosis for the treatment of infants with osteogenesis imperfecta. Both children had severe asymmetrical brachycephaly documented by laser digital scanning and were submitted to treatment with a cranial remolding orthosis. Outcomes and Conclusion: The study showed that there was a significant improvement in cranial proportion and symmetry, with a reduction in the cephalic index at reevaluation. It is concluded that the orthotic therapy is an effective therapeutic modality to improve the proportion and minimize the asymmetry in children with osteogenesis imperfecta. Clinical relevance The clinical relevance of such a description is that children with osteogenesis imperfecta may have numerous deformities and minimizing them can be an important factor. This report showed a beneficial result as the orthotic therapy modality improved the proportions and minimized the asymmetry. This treatment offers too high levels of satisfaction to parents and brings these children closer to normal indices.

  20. A Guide to Education for Children with Osteogenesis Imperfecta. What Is OIF? Care of an Osteogenesis Imperfecta Baby and Child.

    Science.gov (United States)

    Ostegenesis Imperfecta Foundation, Inc., Manchester, NH.

    Three pamphlets provide basic information on the care and education of children with osteogenesis imperfecta (OI) a lifelong liability to fractures due to imperfectly formed "brittle bones." The first brochure, a guide to education for children with OI, addresses the importance of attitudes, the value of early education, public school…

  1. Scanning Еlectron Мicroscopy of Еnamel and Dentin of Тeeth with Hypocalcified Аmelogenesis Imperfecta.

    Science.gov (United States)

    Belcheva, Ani B; Philipov, Ivan At; Tomov, Georgi T

    2016-03-01

    The histological features of teeth with hypocalcified amelogenesis imperfecta (AI) have been poorly studied, which calls into question the effectiveness of modern adhesive techniques used in the treatment of these noncarious defects. The aim of this study was to investigate the morphological features of the enamel and dentin of teeth with AI using scanning electron microscopy (SEM), and compare these features with those of healthy teeth. We examined four primary teeth extracted on indication from a 10-year-old girl with hypocalcified amelogenesis imperfecta. The same number of primary teeth extracted from healthy subjects was used as controls. The morphological characteristics of the enamel and dentin are described after investigating the teeth and photographing the specimens with scanning electron microscope. The SEM photos of the enamel of AI teeth show presence of external defects, incorrectly oriented enamel prisms and enlarged interprism spaces. Thickening of the peritubular dentin and partially obliterated dentinal tubules characterize the dentin of these teeth. The enamel and dentin of teeth affected by hypocalcified AI diff er considerably from normal hard dental structures in their morphological characteristics.

  2. Osteogenesis imperfecta: diagnosis and treatment.

    Science.gov (United States)

    Palomo, Telma; Vilaça, Tatiane; Lazaretti-Castro, Marise

    2017-12-01

    Here we summarize the diagnosis of osteogenesis imperfecta, discuss newly discovered genes involved in osteogenesis imperfecta, and review the management of this disease in children and adults. Mutations in the two genes coding for collagen type I, COL1A1 and COL1A2, are the most common cause of osteogenesis imperfecta. In the past 10 years, defects in at least 17 other genes have been identified as responsible for osteogenesis imperfecta phenotypes, with either dominant or recessive transmission. Intravenous bisphosphonate infusions are the most widely used medical treatment. This has a marked effect on vertebra in growing children and can lead to vertebral reshaping after compression fractures. However, bisphosphonates are less effective for preventing long-bone fractures. At the moment, new therapies are under investigation. Despite advances in the diagnosis and treatment of osteogenesis imperfecta, more research is needed. Bisphosphonate treatment decreases long-bone fracture rates, but such fractures are still frequent. New antiresorptive and anabolic agents are being investigated but efficacy and safety of these drugs, especially in children, need to be better established before they can be used in clinical practice.

  3. Metaphyseal bands in osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Suresh S

    2010-01-01

    Full Text Available An increasing number of patients with osteogenesis imperfecta are undergoing pamidronate therapy to prevent the incidence of fragility fractures. The authors herein report a child aged 3 years who received five cycles of pamidronate, resulting in metaphyseal bands, known as "zebra lines."

  4. Classification of Osteogenesis Imperfecta revisited

    NARCIS (Netherlands)

    van Dijk, F. S.; Pals, G.; van Rijn, R. R.; Nikkels, P. G. J.; Cobben, J. M.

    2010-01-01

    In 1979 Sillence proposed a classification of Osteogenesis Imperfecta (OI) in OI types I, II, III and IV. In 2004 and 2007 this classification was expanded with OI types V-VIII because of distinct clinical features and/or different causative gene mutations. We propose a revised classification of OI

  5. The Spine in Patients With Osteogenesis Imperfecta.

    Science.gov (United States)

    Wallace, Maegen J; Kruse, Richard W; Shah, Suken A

    2017-02-01

    Osteogenesis imperfecta is a genetic disorder of type I collagen. Although multiple genotypes and phenotypes are associated with osteogenesis imperfecta, approximately 90% of the mutations are in the COL1A1 and COL1A2 genes. Osteogenesis imperfecta is characterized by bone fragility. Patients typically have multiple fractures or limb deformity; however, the spine can also be affected. Spinal manifestations include scoliosis, kyphosis, craniocervical junction abnormalities, and lumbosacral pathology. The incidence of lumbosacral spondylolysis and spondylolisthesis is higher in patients with osteogenesis imperfecta than in the general population. Use of diphosphonates has been found to decrease the rate of progression of scoliosis in patients with osteogenesis imperfecta. A lateral cervical radiograph is recommended in patients with this condition before age 6 years for surveillance of craniocervical junction abnormalities, such as basilar impression. Intraoperative and anesthetic considerations in patients with osteogenesis imperfecta include challenges related to fracture risk, airway management, pulmonary function, and blood loss.

  6. Femoral artery thrombosis after internal fixation of a transverse acetabular fracture in a patient with osteogenesis imperfecta type I

    Directory of Open Access Journals (Sweden)

    Morgan Steven J

    2008-01-01

    Full Text Available Abstract Osteogenesis imperfecta is a genetic disorder characterized by increased susceptibility to fractures and vascular injuries due to connective tissue fragility. In this case report, we present a patient with osteogenesis imperfecta type I who sustained a transverse fracture of the right acetabulum while transferring from bed to chair. The fracture was repaired through an ilioinguinal approach. During the surgery, an iatrogenic injury to the femoral artery and vein occurred. This intraoperative complication was salvaged by immediate vascular repair. We discuss the possible causes of iatrogenic vascular injuries in patients with osteogenesis imperfecta. Orthopaedic surgeons should be aware of this potentially devastating complication in this particular patient cohort.

  7. IFITM5 mutations and osteogenesis imperfecta.

    Science.gov (United States)

    Hanagata, Nobutaka

    2016-03-01

    Interferon-induced transmembrane protein 5 (IFITM5) is an osteoblast-specific membrane protein that has been shown to be a positive regulatory factor for mineralization in vitro. However, Ifitm5 knockout mice do not exhibit serious bone abnormalities, and thus the function of IFITM5 in vivo remains unclear. Recently, a single point mutation (c.-14C>T) in the 5' untranslated region of IFITM5 was identified in patients with osteogenesis imperfecta type V (OI-V). Furthermore, a single point mutation (c.119C>T) in the coding region of IFITM5 was identified in OI patients with more severe symptoms than patients with OI-V. Although IFITM5 is not directly involved in the formation of bone in vivo, the reason why IFITM5 mutations cause OI remains a major mystery. In this review, the current state of knowledge of OI pathological mechanisms due to IFITM5 mutations will be reviewed.

  8. CT findings of osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Kojo, Nobuto; Otsuru, Katsuyasu; Lee, Soichi; Takagi, Shigeyuki; Shigemori, Minoru.

    1987-08-01

    Two cases of osteogenesis imperfecta found in one family (father and daughter) are reported, and the CT findings are described. Case 1 is a 58-year-old man who fell and struck his head at home on November 10, 1984. He was transferred to Omuta City Hospital when he became semicomatose and decerebrate posturing was noted. His family history revealed 8 persons with osteogenesis imperfecta. A skull X-ray film showed a large skull vault, many wormian bones at the lambdoid suture, platybasia, and a basilar impression. A CT scan demonstrated a right acute subdural hematoma, while the bone image showed well-developed mastoid air cells and a skull deformity characteristic of osteogenesis imperfecta. He had an emergency operation, and a 170-gr clot was successfully evacuated. A postoperative CT scan demonstrated brain atrophy, possibly present before head trauma. Case 2 is the daughter of Case 1 (a 27-year-old woman). She also showed characteristic neuroradiological manifestations on a plain skull film and on a CT scan. A basilar impression and platybasia were also demonstrated. In this report, the possible mechanism of the production of a traumatic acute subdural hematoma is also discussed.

  9. Treatment Concepts of Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Ramji Lal Sahu

    2012-06-01

    Full Text Available Background: To explore the Application of the intramedullary nails for correction of deformity in the lower limbs and decrease the opportunity of refractures in children with osteogenesis imperfecta.Materials and Methods: From July 2005 to July 2009, 11 patients (5 males and 6 females, were recruited from Emergency and outpatient department having deformities of osteogenesis imperfecta in lower limbs. With 3 femurs and 5 tibias with deformity in lower limps were corrected by multiosteotomy and fixed with intramedullary interlocking nails, 6 (3 femurs and 3 tibias for Rush nails; 6 (2 femurs and 4 tibias for Ender nails; and 12 (6 femurs and 6 tibias for flexible intramedullary nails. All patients were operated under general or spinal anesthesia. Results: All deformities were perfectly corrected. All patients were available at final follow up, for 9 months to 36 months, mean 18 months. 2 patients had delayed union, 2 had superficial infection in the incision or pin tract, and 1 had refractures postoperatively. The results were excellent in 72.727% and good in 27.272% patients. Conclusion: Multiosteotomy and fixed intramedullary nails can correct the deformity in the lower limbs perfectly and decrease the opportunity of refractures in children with osteogenesis imperfecta, which has been proved to be a reliable method.

  10. CT findings of osteogenesis imperfecta

    International Nuclear Information System (INIS)

    Kojo, Nobuto; Otsuru, Katsuyasu; Lee, Soichi; Takagi, Shigeyuki; Shigemori, Minoru.

    1987-01-01

    Two cases of osteogenesis imperfecta found in one family (father and daughter) are reported, and the CT findings are described. Case 1 is a 58-year-old man who fell and struck his head at home on November 10, 1984. He was transferred to Omuta City Hospital when he became semicomatose and decerebrate posturing was noted. His family history revealed 8 persons with osteogenesis imperfecta. A skull X-ray film showed a large skull vault, many wormian bones at the lambdoid suture, platybasia, and a basilar impression. A CT scan demonstrated a right acute subdural hematoma, while the bone image showed well-developed mastoid air cells and a skull deformity characteristic of osteogenesis imperfecta. He had an emergency operation, and a 170-gr clot was successfully evacuated. A postoperative CT scan demonstrated brain atrophy, possibly present before head trauma. Case 2 is the daughter of Case 1 (a 27-year-old woman). She also showed characteristic neuroradiological manifestations on a plain skull film and on a CT scan. A basilar impression and platybasia were also demonstrated. In this report, the possible mechanism of the production of a traumatic acute subdural hematoma is also discussed. (author)

  11. Osteogenesis Imperfecta (Type IV with Dental Findings in Siblings

    Directory of Open Access Journals (Sweden)

    Shishir Ram Shetty

    2011-01-01

    Full Text Available Osteogenesis imperfecta (OI is a hereditary disorder characterized by increased tendency for bone fractures due to high fragility. The clinical and radiological features of OI manifest in different age groups, although the disease is congenital in nature. Besides bone fragility, features like laxity of the ligaments, blue sclera, growth retardation, and scoliosis are also observed. In severe cases, respiratory distress and death have been reported. The most important oral finding in OI is the presence of yellowish-brown-coloured brittle teeth characteristic of dentinogenesis imperfecta. Genetic factors play a very important role in the pathogenesis of OI either as a dominant or recessive factor. When a child has OI, there is a 25% chance of the sibling to have the same disorder. We report two cases of OI in siblings born to parents with a history of consanguineous marriage. The clinical and radiological features of the two cases are described in detail.

  12. Pathophysiology and therapeutic options in osteogenesis imperfecta: an update

    Directory of Open Access Journals (Sweden)

    Brizola E

    2016-03-01

    Full Text Available Evelise Brizola,1 Temis M Félix,2 Jay R Shapiro3 1Bone and Osteogenesis Imperfecta Department, Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA; 2Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Osteoporosis and Metabolic Bone Disorders Center, Bethesda, MD, USAAbstract: Osteogenesis imperfecta (OI is a rare, heritable systemic disorder of bone and connective tissue, which in almost 90% of cases is due to mutations affecting the normal synthesis of type I collagen. In 1979, four OI phenotypes were categorized which were inherited as autosomal dominant characteristics. Individuals with OI present both genetic and phenotypic variabilities. Major characteristics of OI are bone fragility, blue sclerae, dentinogenesis imperfecta, short stature, scoliosis, and joint hyperextensibility. Both autosomal dominant and recessive inheritance are now recognized. Advances in molecular diagnosis have led to a major expansion in our understanding of the genetic basis for different OI phenotypes. To date, sequence variants in 17 genes are described as causative of OI. These genes regulate the synthesis of type I collagen pro-alpha polypeptide chains, proteins involved in type I collagen processing in the endoplasmic reticulum and proteins involved in osteoblast function. These new genetic associations have also led to uncertainty with regard to the current classification of OI phenotypes. Bisphosphonates have been widely used to improve bone mass and decrease fractures in both children and adults with OI. While effective in many but not all children when administered for 2–4 years, bisphosphonates have not proven effective in adults with OI. Studies are limited for treatment of adults with teriparatide and denosumab. Advances have been reported in the surgical management of OI. Although the role of physical therapy in the management

  13. Osteogenesis imperfecta: from diagnosis and multidisciplinary treatment to future perspectives.

    Science.gov (United States)

    Bregou Bourgeois, Aline; Aubry-Rozier, Bérengère; Bonafé, Luisa; Laurent-Applegate, Lee; Pioletti, Dominique P; Zambelli, Pierre-Yves

    2016-01-01

    Osteogenesis imperfecta is an inherited connective tissue disorder with wide phenotypic and molecular heterogeneity. A common issue associated with the molecular abnormality is a disturbance in bone matrix synthesis and homeostasis inducing bone fragility. In very early life, this can lead to multiple fractures and progressive bone deformities, including long bone bowing and scoliosis. Multidisciplinary management improves quality of life for patients with osteogenesis imperfecta. It consists of physical therapy, medical treatment and orthopaedic surgery as necessary. Medical treatment consists of bone-remodelling drug therapy. Bisphosphonates are widely used in the treatment of moderate to severe osteogenesis imperfecta, from infancy to adulthood. Other more recent drug therapies include teriparatide and denosumab. All these therapies target the symptoms and have effects on the mechanical properties of bone due to modification of bone remodelling, therefore influencing skeletal outcome and orthopaedic surgery. Innovative therapies, such as progenitor and mesenchymal stem cell transplantation, targeting the specific altered pathway rather than the symptoms, are in the process of development.

  14. Recent developments in osteogenesis imperfecta

    Science.gov (United States)

    Shaker, Joseph L.; Albert, Carolyne; Fritz, Jessica; Harris, Gerald

    2015-01-01

    Osteogenesis imperfecta (OI) is an uncommon genetic bone disease associated with brittle bones and fractures in children and adults. Although OI is most commonly associated with mutations of the genes for type I collagen, many other genes (some associated with type I collagen processing) have now been identified. The genetics of OI and advances in our understanding of the biomechanical properties of OI bone are reviewed in this article. Treatment includes physiotherapy, fall prevention, and sometimes orthopedic procedures. In this brief review, we will also discuss current understanding of pharmacologic therapies for treatment of OI. PMID:26401268

  15. A study of dentinogenesis imperfecta

    International Nuclear Information System (INIS)

    Choi, Eui Whan

    1992-01-01

    The author observed a case of dentinogenesis imperfecta in a 8-year-old and a 9-year old brother with complaints of abnormal morphologic changes of the teeth. 1. Clinically, yellowish brown colored teeth, fractured crown and numerous retained root tips of edciduous teeth with severe attrition were observed in the both deciduous and permanent dentitions. 2. Radiographically, small-sized teeth partial or complete obliteration of the pulp chambers and pulp canals in the anterior teeth, partial obliteration of the pulp chambers and thin enamel in the permanent tooth germs were observed. 3. The familial history was their father has been lose his teeth early.

  16. What Are the Symptoms of Osteogenesis Imperfecta?

    Science.gov (United States)

    ... most of which occur before puberty or after middle age Motor skill delays People with type IV often ... A, Cabral WA, Barnes AM, & Marini JC. (2011). New Perspectives on Osteogenesis Imperfecta. Nat Rev Endocrinol, Jun ...

  17. Osteogenesis imperfecta in childhood: impairment and disability

    NARCIS (Netherlands)

    Engelbert, R. H.; van der Graaf, Y.; van Empelen, R.; Beemer, F. A.; Helders, P. J.

    1997-01-01

    To determine clinical characteristics in children with osteogenesis imperfecta (OI) regarding impairment (range of joint motion and muscle strength) and disability (functional skills) in relation to the different types of the disease, and to study the correlation between characteristics of

  18. Osteogenesis Imperfecta in Pregnancy: Case Report

    Directory of Open Access Journals (Sweden)

    Maryam Rabiee

    2011-03-01

    Full Text Available Osteogenesis imperfecta is a rare inherited Connective tissue disorder with an expression that varies from mild to severe disease affecting bone, Sclera and middle ear. Fertility is preserved, especially in those patients with type 1. We present hereby a pregnant woman with Osteogenesis imperfecta that had over 30 fractures in long bones and vertebrae. The object of this report was to determine choice of delivery method, maternal and neonatal Complications and prenatal diagnosis.

  19. Osteogenesis Imperfecta: A Review with Clinical Examples

    Science.gov (United States)

    van Dijk, F.S.; Cobben, J.M.; Kariminejad, A.; Maugeri, A.; Nikkels, P.G.J.; van Rijn, R.R.; Pals, G.

    2011-01-01

    Osteogenesis imperfecta (OI) is characterized by susceptibility to bone fractures, with a severity ranging from subtle increase in fracture frequency to prenatal fractures. The first scientific description of OI dates from 1788. Since then, important milestones in OI research and treatment have, among others, been the classification of OI into 4 types (the ‘Sillence classification’), the discovery of defects in collagen type I biosynthesis as a cause of most cases of OI and the use of bisphosphonate therapy. Furthermore, in the past 5 years, it has become clear that OI comprises a group of heterogeneous disorders, with an estimated 90% of cases due to a causative variant in the COL1A1 or COL1A2 genes and with the remaining 10% due to causative recessive variants in the 8 genes known so far, or in other currently unknown genes. This review aims to highlight the current knowledge around the history, epidemiology, pathogenesis, clinical/radiological features, management, and future prospects of OI. The text will be illustrated with clinical descriptions, including radiographs and, where possible, photographs of patients with OI. PMID:22570641

  20. Prenatal Diagnosis of Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Özgür Özyüncü

    2010-04-01

    Full Text Available Skeletal dysplasias are a group of diseases with a wide spectrum related to bone and cartilage. Some forms are lethal whereas some forms have milder clinical progression. Prenatal diagnosis of skeletal dysplasias may be possible especially when there is an index case in the family. Ultrasonography plays the central role in prenatal diagnosis and most common sonographic features are angulation of long bones, bending of femur or bowing signin the long bones. We present a case whose follow up for fetal short extremities ended with termination of pregnancy. The differential diagnosis is hard and depend especially on the fetal x-ray. Final diagnosis was lethal type osteogenesis imperfecta.

  1. Update on the evaluation and treatment of osteogenesis imperfecta.

    Science.gov (United States)

    Harrington, Jennifer; Sochett, Etienne; Howard, Andrew

    2014-12-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that presents with a wide clinical phenotype spectrum: from perinatal lethality and severe deformities to very mild forms without fractures. Most cases of OI are due to autosomal dominant mutations of the type I collagen genes. A multidisciplinary approach with rehabilitation, orthopedic surgery, and consideration of medical therapy with bisphosphonates underpins current management. Greater understanding of the pathogenesis of OI may lead to novel, therapeutic approaches to help improve clinical symptoms of children with OI in the future. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Type III Osteogenesis Imperfecta With Dentinogenesis Imperfecta - A Case Report And review of Literature

    Directory of Open Access Journals (Sweden)

    Prabal Pal

    2003-01-01

    Full Text Available Osteogenesis Imperfecta is a genetic disorder affecting approximately 20,000 U.S. population with multiple fracture of the bone. The, actual literature of the number of patients suffering from Osteogenesis Impcrfecta in Indian Population is still nor available. This is a case of a male patient who presented to the O.PD. of Subharati Dental College with history of pain ands swelling in the left lower posterior teeth region. On detail workout of the case it was found that the patient had Dentinogenesis Imperfecta Type I with Type III Osteogenesis Imperfecta. Very few cases with such presentation is reported in Indian Literature. The following report presents the clinical findings of Osteogcnesis Imperfecta and an associated review of Literature.

  3. New Perspectives on Osteogenesis Imperfecta

    Science.gov (United States)

    Forlino, Antonella; Cabral, Wayne A.; Barnes, Aileen M.; Marini, Joan C.

    2012-01-01

    A new paradigm has emerged for osteogenesis imperfecta (OI) as a collagen-related disorder. The more prevalent autosomal dominant forms of OI are caused by primary defects in type I collagen, while autosomal recessive forms are caused by deficiency of proteins which interact with type I procollagen for post-translational modification and/or folding. Factors contributing to the mechanism of dominant OI include intracellular stress, disruption of interactions between collagen and non-collagenous proteins, compromised matrix structure, abnormal cell-cell and cell-matrix interactions and tissue mineralization. Recessive OI is caused by deficiency of any of the three components of the collagen prolyl 3-hydroxylation complex; absence of 3-hydroxylation is associated with increased modification of the collagen helix, supporting delayed collagen folding. Other causes of recessive OI include deficiency of collagen chaperones, FKBP65 or HSP47. Murine models are crucial to uncovering the common pathways in dominant and recessive OI bone dysplasia. Clinical management of OI is multidiscipinary, encompassing substantial progress in physical rehabilitation and surgical procedures, managment of hearing, dental and pulmonary abnormalities, as well as drugs such as bisphosphonates and rGH. Novel treatments using cell therapy or new drug regimens hold promise for the future. PMID:21670757

  4. Hearing Loss in Osteogenesis Imperfecta: Characteristics and Treatment Considerations

    Science.gov (United States)

    Pillion, Joseph P.; Vernick, David; Shapiro, Jay

    2011-01-01

    Osteogenesis imperfecta (OI) is the most common heritable disorder of connective tissue. It is associated with fractures following relatively minor injury, blue sclerae, dentinogenesis imperfecta, increased joint mobility, short stature, and hearing loss. Structures in the otic capsule and inner ear share in the histologic features common to other skeletal tissues. OI is due to mutations involving several genes, the most commonly involved are the COL1A1 or COL1A2 genes which are responsible for the synthesis of the proalpha-1 and proalpha-2 polypeptide chains that form the type I collagen triple helix. A genotype/phenotype relationship to hearing loss has not been established in OI. Hearing loss is commonly found in OI with prevalence rates ranging from 50 to 92% in some studies. Hearing loss in OI may be conductive, mixed, or sensorineural and is more common by the second or third decade. Treatment options such as hearing aids, stapes surgery, and cochlear implants are discussed. PMID:22567374

  5. Clinical Features of Osteogenesis Imperfecta in Taiwan

    Directory of Open Access Journals (Sweden)

    Hsiang-Yu Lin

    2009-07-01

    Conclusion: Nine of the 11 clinical features examined—height, weight, BMD, dentinogenesis imperfecta, bone deformity, scoliosis, walking ability, fracture rate, and family history—were significantly different among the three types of OI patients. This finding may be of help in evaluating patients and establishing their prognosis.

  6. Cardiovascular Involvement in Children with Osteogenesis Imperfecta

    Science.gov (United States)

    Karamifar, Hamdollah; Ilkhanipoor, Homa; Ajami, Gholamhossein; Karamizadeh, Zohreh; Amirhakimi, Gholamhossein; Shakiba, Ali-Mohammad

    2013-01-01

    Objective Osteogenesis imperfecta is a hereditary disease resulting from mutation in type I procollagen genes. One of the extra skeletal manifestations of this disease is cardiac involvement. The prevalence of cardiac involvement is still unknown in the children with osteogenesis imperfecta. The present study aimed to investigate the prevalence of cardiovascular abnormalities in these patients. Methods 24 children with osteogenesis imperfecta and 24 normal children who were matched with the patients regarding sex and age were studied. In both groups, standard echocardiography was performed, and heart valves were investigated. Dimensions of left ventricle, aorta annulus, sinotubular junction, ascending and descending aorta were measured and compared between the two groups. Findings The results revealed no significant difference between the two groups regarding age, sex, ejection fraction, shortening fraction, mean of aorta annulus, sinotubular junction, ascending and descending aorta, but after correction based on the body surface area, dimensions of aorta annulus, sinotubular junction, ascending and descending aorta in the patients were significantly higher than those in the control group (P25 mmHg and one patient had pulmonary insufficiency with indirect evidence of pulmonary hypertension. According to Z scores of aorta annulus, sinotubular junction and ascending aorta, 5, 3, and 1 out of 24 patients had Z scores >2 respectively. Conclusion The prevalence of valvular heart diseases and aortic root dilation was higher in children with osteogenesis imperfecta. In conclusion, cardiovascular investigation is recommended in these children. PMID:24800009

  7. Physical training in children with osteogenesis imperfecta

    NARCIS (Netherlands)

    van Brussel, Marco; Takken, Tim; Uiterwaal, Cuno S. P. M.; Pruijs, Hans J.; van der Net, Janjaap; Helders, Paul J. M.; Engelbert, Raoul H. H.

    2008-01-01

    To study the effects of a physical training program on exercise capacity, muscle force, and subjective fatigue levels in patients with mild to moderate forms of osteogenesis imperfecta (OI). Thirty-four children with OI type I or IV were randomly assigned to either a 12-week graded exercise program

  8. Osteogenesis imperfecta: klinische en genetische heterogeniteit

    NARCIS (Netherlands)

    van Dijk, Fleur S.; Cobben, Jan M.; Maugeri, Alessandra; Nikkels, Peter G. J.; van Rijn, Rick R.; Pals, Gerard

    2012-01-01

    Osteogenesis imperfecta is a hereditary connective tissue disorder characterized primarily by fractures with no or small causal antecedent; in most patients this is a consequence of diminished or abnormal production of collagen type I. It is a clinically heterogeneous disorder: it has been proposed

  9. Osteogenesis imperfecta with joint contractures: Bruck syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Blacksin, M.F. [Department of Radiology, University of Medicine and Dentistry of New Jersey, 150 Bergen St., Rm. C320, Newark, NJ 07103-2426 (United States); Pletcher, B.A. [Center for Human and Molecular Genetics, Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Newark, New Jersey (United States); David, M. [Department of Radiology, Newark-Beth Israel Medical Center, Newark, New Jersey (United States)

    1998-02-01

    We describe an Egyptian boy with osteogenesis imperfecta who was born with thumb contractures and bilateral antecubital pterygia. He was seen at 16 months of age with femur and tibial fractures, thoracic vertebral compression fractures, scoliosis and Wormian bones. The findings are consistent with a diagnosis of Bruck syndrome. (orig.) With 1 fig., 5 refs.

  10. PICTORIAL INTERLUDES Perinatal lethal osteogenesis imperfecta

    African Journals Online (AJOL)

    Osteogenesis imperfecta (OI) is a heterogeneous group of genetic bone disorders that are characterised by decreased bone mass, increased bone fragility and susceptibility to fractures. The severe ... in the collagen 1 alpha-1 chain (COL1A1) and collagen 1 alpha-2 chain. (COL1A2) genes. They encode the two chains pro ...

  11. Heart disease in patients with osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Ashournia, Hamoun; Johansen, Frank Ted; Folkestad, Lars

    2015-01-01

    INTRODUCTION: Osteogenesis imperfecta (OI) is a rare, inherited systemic connective tissue disease that causes decreased bioavailability of collagen type 1. Collagen type 1 is the most abundant connective tissue in the body and a key part of many organs. While the bone phenotype in OI is well des...

  12. Spondylolisthesis caused by extreme pedicle elongation in osteogenesis imperfecta

    OpenAIRE

    Ivo, Roland; Fuerderer, Sebastian; Eysel, Peer

    2007-01-01

    Although osteogenesis imperfecta is a well-known skeletal disorder, reports of spondylolisthesis in osteogenesis imperfecta are rare. Only very few cases of spondylolisthesis caused by elongation of lumbar pedicles have been described in the literature. Here we report three patients suffering from osteogenesis imperfecta showing a severe form of hyperlordosis caused by lumbar pedicle elongation and consecutive spondylolisthesis. Radiographs in the course of childhood and adolescence show a ra...

  13. Ebstein's anomaly in a child with osteogenesis imperfecta type I.

    Science.gov (United States)

    D'Eufemia, Patrizia; Celli, Mauro; Versacci, Paolo; Zambrano, Anna; Lodato, Valentina; Persiani, Pietro; Sangiorgi, Luca

    2011-05-01

    Cardiovascular involvement is relatively rare in osteogenesis imperfecta and has a predilection for left-sided cardiac valves. We report a 5 years old female child affected by osteogenesis imperfecta type I in which an asymptomatic mild form of Ebstein's anomaly, a congenital tricuspid malformation, was diagnosed during routinely investigation. The association of these two relatively rare entities could provide new insight to better understand the pathogenesis of cardiac involvement in osteogenesis imperfecta.

  14. OSTEOGENESIS IMPERFECTA AND PREGNANCY: PROBLEMS EVOLVING BY THE TIME OF DELIVERY

    Directory of Open Access Journals (Sweden)

    S. R. Mravyan

    2015-01-01

    Full Text Available The article describes a case of pregnancy in a patient with osteogenesis imperfecta. It is of note that both local and foreign medicine this disorder is a contraindication to pregnancy due to a high risk of maternal and fetal complications. The authors review literature on pre-pregnancy planning and preparation, pregnancy management, types of deliveries and approaches to anesthesia in female patients with osteogenesis imperfecta. Special attention is paid to anesthesiological complications during delivery, ways of their management and correction. Due to a high inheritance rate of this disorder, genetic consulting and extracorporeal fertilization methods are of great importance.

  15. Behavior of scoliosis during growth in children with osteogenesis imperfecta.

    Science.gov (United States)

    Anissipour, Alireza K; Hammerberg, Kim W; Caudill, Angela; Kostiuk, Theodore; Tarima, Sergey; Zhao, Heather Shi; Krzak, Joseph J; Smith, Peter A

    2014-02-05

    Spinal deformities are common in patients with osteogenesis imperfecta, a heritable disorder that causes bone fragility. The purpose of this study was to describe the behavior of spinal curvature during growth in patients with osteogenesis imperfecta and establish its relationship to disease severity and medical treatment with bisphosphonates. The medical records and radiographs of 316 patients with osteogenesis imperfecta were retrospectively reviewed. The severity of osteogenesis imperfecta was classified with the modified Sillence classification. Serial curve measurements were recorded throughout the follow-up period for each patient with scoliosis. Regression analysis was used to determine the effect of disease severity (Sillence type), patient age, and bisphosphonate treatment on the progression of scoliosis as measured with the Cobb method. Of the 316 patients with osteogenesis imperfecta, 157 had associated scoliosis, a prevalence of 50%. Scoliosis prevalence (68%) and mean progression rate (6° per year) were the highest in the group of patients with the most severe osteogenesis imperfecta (modified Sillence type III). A group with intermediate osteogenesis imperfecta severity, modified Sillence type IV, demonstrated intermediate scoliosis values (54%, 4° per year). The patient group with the mildest form of osteogenesis imperfecta, modified Sillence type I, had the lowest scoliosis prevalence (39%) and rate of progression (1° per year). Early treatment-before the patient reached the age of six years-of type-III osteogenesis imperfecta with bisphosphonate therapy decreased the curve progression rate by 3.8° per year, which was a significant decrease. Bisphosphonate treatment had no demonstrated beneficial effect on curve behavior in patients with other types of osteogenesis imperfecta or in patients of older age. The prevalence of scoliosis in association with osteogenesis imperfecta is high. Progression rates of scoliosis in children with osteogenesis

  16. Lethal/severe osteogenesis imperfecta in a large family: a novel homozygous LEPRE1 mutation and bone histological findings

    NARCIS (Netherlands)

    van Dijk, Fleur S.; Nikkels, Peter G. J.; den Hollander, Nicolette S.; Nesbitt, Isabel M.; van Rijn, Rick R.; Cobben, Jan M.; Pals, Gerard

    2011-01-01

    We report a large consanguineous Turkish family in which multiple individuals are affected with autosomal recessive lethal or severe osteogenesis imperfecta (OI) due to a novel homozygous LEPRE1 mutation. In one affected individual histological studies of bone tissue were performed, which may

  17. Osteogenesis imperfecta Type IV: a newly identified variant at ...

    African Journals Online (AJOL)

    Osteogenesis imperfecta is a clinically heterogenous disease caused by defective collagen syntesis associated with a mutation in the COL1A1 or COL1A2 genes. In this report, we present a case of osteogenesis imperfecta (OI) type IV, seen in a female fetus with incurved femurs at 18 weeks of gestation. Molecular analysis ...

  18. The clinical features of osteogenesis imperfecta in Vietnam.

    Science.gov (United States)

    Binh, Ho Duy; Maasalu, Katre; Dung, Vu Chi; Ngoc, Can T Bich; Hung, Ton That; Nam, Tran V; Nhan, Le N Thanh; Prans, Ele; Reimann, Ene; Zhytnik, Lidiia; Kõks, Sulev; Märtson, Aare

    2017-01-01

    Osteogenesis imperfecta (OI) has not been studied in a Vietnamese population before. The aim of this study was to systematically collect epidemiological information, investigate clinical features and create a clinical database of OI patients in Vietnam for future research and treatment strategy development. Participants underwent clinical and physical examinations; also medical records were reviewed. Genealogical information was collected and family members' phenotypical manifestations recorded. Cases were classified according to the Sillence classification. In total, 146 OI patients from 120 families were studied: 46 with OI Type I, 46 with Type III and 54 with Type IV. Almost patients had skeletal deformations. One hundred and forty-two had a history of fractures, 117 blue sclera, 89 dentinogenesis imperfecta and 26 hearing loss. The total number of fractures was 1,932. Thirty-four patients had intra-uterine fractures and nine had perinatal fractures. Surgery was performed 163 times in 58 patients; 100 osteosyntheses and 63 osteotomies. Bisphosphonate treatment was used in 37 patients. The number of affected individuals and predominance of severe forms of OI indicate that the disease is under diagnosed in Vietnam, especially in cases without a family history or with mild form of OI. Deformities appeared in all patients with different severity and localisation, affecting mostly the lower limbs. OI medical and surgical treatment rates are low and in most cases surgery was performed due to fractures. Compared to previous studies, our results indicate a lower OI prevalence and greater severity of symptoms in the Vietnamese population when compared with other areas. Further investigation, improved diagnosis and treatment are needed to increase the patients' quality of life.

  19. Bone properties by nanoindentation in mild and severe osteogenesis imperfecta.

    Science.gov (United States)

    Albert, Carolyne; Jameson, John; Toth, Jeffrey M; Smith, Peter; Harris, Gerald

    2013-01-01

    Osteogenesis imperfecta is a heterogeneous genetic disorder characterized by bone fragility. Previous research suggests that impaired collagen network and abnormal mineralization affect bone tissue properties, however, little data is yet available to describe bone material properties in individuals with this disorder. Bone material properties have not been characterized in individuals with the most common form of osteogenesis imperfecta, type I. Bone tissue elastic modulus and hardness were measured by nanoindentation in eleven osteotomy specimens that were harvested from children with osteogenesis imperfecta during routine surgeries. These properties were compared between osteogenesis imperfecta types I (mild, n=6) and III (severe, n=5), as well as between interstitial and osteonal microstructural regions using linear mixed model analysis. Disease severity type had a small but statistically significant effect on modulus (7%, P=0.02) and hardness (8%, Posteogenesis imperfecta type I had higher modulus and hardness than did those with type III. Overall, mean modulus and hardness values were 13% greater in interstitial lamellar bone regions than in osteonal regions (Posteogenesis imperfecta, i.e., type I. Results indicate that intrinsic bone tissue properties are affected by phenotype. Knowledge of the material properties of bones in osteogenesis imperfecta will contribute to the ability to develop models to assist in predicting fracture risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Osteogenesis Imperfecta, Pseudoachalasia, and Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Dilsa Mizrak

    2015-01-01

    Full Text Available Osteogenesis imperfecta (OI is a rare, inherited skeletal disorder characterized by abnormalities of type 1 collagen. Malignancy is rarely reported in patients with OI and it was suggested that this disease can protect against cancer. Here, we report a 41-year-old woman with symptoms of achalasia where repeated treatment of pneumatic dilation and stent replacement was unsuccessful; therefore, surgery was performed. Pathology showed gastric adenocarcinoma unexpectedly. Chemotherapy was given after assessing dihydropyrimidine dehydrogenase (DPD enzyme activity, which can be deficient in OI patients. This is the first report of gastric cancer mimicking achalasia in a patient with OI.

  1. Expression of steroid receptors in ameloblasts during amelogenesis in rat incisors

    Directory of Open Access Journals (Sweden)

    Sophia Houari

    2016-11-01

    Full Text Available Endocrine disrupting chemicals (EDCs play a part in the modern burst of diseases and interfere with the steroid hormone axis. Bisphenol A (BPA, one of the most active and widely used EDCs, affects ameloblast functions, leading to an enamel hypomineralization pattern similar to that of Molar Incisor Hypomineralization (MIH. In order to explore the molecular pathways stimulated by BPA during amelogenesis, we thoroughly investigated the receptors known to directly or indirectly mediate the effects of BPA. The expression patterns of high affinity BPA receptors (ERRγ, GPR30, of ketosteroid receptors (ERs, AR, PGR, GR, MR, of the retinoid receptor RXRα and PPARγ were established using RT-qPCR analysis of RNAs extracted from microdissected enamel organ of adult rats. Their expression was dependent on the stage of ameloblast differentiation, except that of ERβ and PPARγ which remained undetectable. An additional large scale microarray analysis revealed three main groups of receptors according to their level of expression in maturation stage ameloblasts. The expression level of RXRα was the highest, similar to the vitamin D receptor (VDR, whereas the others were 13 to 612 fold lower, with AR and GR being intermediate. Immunofluorescent analysis of VDR, ERα and AR confirmed their presence mainly in maturation- stage ameloblasts. These data provide further evidence that ameloblasts express a specific combination of hormonal receptors depending on their developmental stage. This study represents the first step towards understanding dental endocrinology as well as some of the effects of EDCs on the pathophysiology of amelogenesis.

  2. Expression of Steroid Receptors in Ameloblasts during Amelogenesis in Rat Incisors

    Science.gov (United States)

    Houari, Sophia; Loiodice, Sophia; Jedeon, Katia; Berdal, Ariane; Babajko, Sylvie

    2016-01-01

    Endocrine disrupting chemicals (EDCs) play a part in the modern burst of diseases and interfere with the steroid hormone axis. Bisphenol A (BPA), one of the most active and widely used EDCs, affects ameloblast functions, leading to an enamel hypomineralization pattern similar to that of Molar Incisor Hypomineralization (MIH). In order to explore the molecular pathways stimulated by BPA during amelogenesis, we thoroughly investigated the receptors known to directly or indirectly mediate the effects of BPA. The expression patterns of high affinity BPA receptors (ERRγ, GPR30), of ketosteroid receptors (ERs, AR, PGR, GR, MR), of the retinoid receptor RXRα, and PPARγ were established using RT-qPCR analysis of RNAs extracted from microdissected enamel organ of adult rats. Their expression was dependent on the stage of ameloblast differentiation, except that of ERβ and PPARγ which remained undetectable. An additional large scale microarray analysis revealed three main groups of receptors according to their level of expression in maturation-stage ameloblasts. The expression level of RXRα was the highest, similar to the vitamin D receptor (VDR), whereas the others were 13 to 612-fold lower, with AR and GR being intermediate. Immunofluorescent analysis of VDR, ERα and AR confirmed their presence mainly in maturation- stage ameloblasts. These data provide further evidence that ameloblasts express a specific combination of hormonal receptors depending on their developmental stage. This study represents the first step toward understanding dental endocrinology as well as some of the effects of EDCs on the pathophysiology of amelogenesis. PMID:27853434

  3. How Do Health Care Providers Diagnose Osteogenesis Imperfecta?

    Science.gov (United States)

    ... Share Facebook Twitter Pinterest Email Print How do health care providers diagnose osteogenesis imperfecta (OI)? If OI is moderate or severe, health care providers usually diagnose it during prenatal ultrasound at ...

  4. Challenges of Fracture Management for Adults With Osteogenesis Imperfecta.

    Science.gov (United States)

    Gil, Joseph A; DeFroda, Steven F; Sindhu, Kunal; Cruz, Aristides I; Daniels, Alan H

    2017-01-01

    Osteogenesis imperfecta is caused by qualitative or quantitative defects in type I collagen. Although often considered a disease with primarily pediatric manifestations, more than 25% of lifetime fractures are reported to occur in adulthood. General care of adults with osteogenesis imperfecta involves measures to preserve bone density, regular monitoring of hearing and dentition, and maintenance of muscle strength through physical therapy. Surgical stabilization of fractures in these patients can be challenging because of low bone mineral density, preexisting skeletal deformities, or obstruction by instrumentation from previous surgeries. Additionally, unique perioperative considerations exist when operatively managing fractures in patients with osteogenesis imperfecta. To date, there is little high-quality literature to help guide the optimal treatment of fractures in adult patients with osteogenesis imperfecta. [Orthopedics. 2017; 40(1):e17-e22.]. Copyright 2016, SLACK Incorporated.

  5. Hyperplastic callus formation in osteogenesis imperfecta. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Burchardt, A.J. (Depts. of Radiology and Pediatric Orthopedic Surgery, Rigshospitalet, Copenhagen Univ. (Denmark)); Wagner, A.A. (Depts. of Radiology and Pediatric Orthopedic Surgery, Rigshospitalet, Copenhagen Univ. (Denmark)); Basse, P. (Depts. of Radiology and Pediatric Orthopedic Surgery, Rigshospitalet, Copenhagen Univ. (Denmark))

    1994-09-01

    We report a case of bilateral hyperplastic callus formation as a complication of fracture in a patient with osteogenesis imperfecta. The clinical and radiographic findings and the differential diagnosis are discussed. (orig.).

  6. Audiologic phenotype of osteogenesis imperfecta: use in clinical differentiation.

    NARCIS (Netherlands)

    Swinnen, F.K.R.; Dhooge, I.J.; Coucke, P.J.; D'Eufemia, P.; Zardo, F.; Garretsen, T.J.; Cremers, C.W.R.J.; Leenheer, E.M. De

    2012-01-01

    OBJECTIVES: To describe the audiologic phenotype in osteogenesis imperfecta (OI). STUDY DESIGN: Observational study. SETTING: Tertiary referral center. PATIENTS: One hundred eighty-two patients with genetically confirmed OI, aged 3 to 89 years. INTERVENTION: Diagnostic hearing evaluation through

  7. Osteogenesis Imperfecta:No Place for Imperfect Anaesthesiologist

    Directory of Open Access Journals (Sweden)

    Geeta Bhandari

    2008-01-01

    Full Text Available Osteogenesis imperfecta, an inherited disease of connective tissue, is associated with anatomic and physiologic abnormalities which make any form of anaesthesia a challenging task for the anaesthesiologist. We report a case of Osteogenesis imperfecta type -IV with severe anatomic deformities, who underwent replacement nailing procedure for periprosthetic fracture of shaft femur under general anaesthesia. We used a proseal LMA in the case, patient suffered a posterior dislocation of right shoulder on repositioning at the end of the surgery.

  8. Osteogenesis Imperfecta:No Place for Imperfect Anaesthesiologist

    OpenAIRE

    Geeta Bhandari; K S Shahi; Poonam Bhadoria; Anju R Bhalotra; O D Sandhya; Mona Arya

    2008-01-01

    Osteogenesis imperfecta, an inherited disease of connective tissue, is associated with anatomic and physiologic abnormalities which make any form of anaesthesia a challenging task for the anaesthesiologist. We report a case of Osteogenesis imperfecta type -IV with severe anatomic deformities, who underwent replacement nailing procedure for periprosthetic fracture of shaft femur under general anaesthesia. We used a proseal LMA in the case, patient suffered a posterior dislocation of right shou...

  9. [Genetic heterogeneity of osteogenesis imperfecta. Study of 6 cases].

    Science.gov (United States)

    Olivares, J L; Hernández, M C; Bueno, M

    1986-09-01

    Osteogenesis imperfecta one of the most common disorders of connective tissue, has been known for centuries. The most characteristic alterations which define it are: osteoporosis, osseous fragility with multiple fractures, blue sclerae, deafness and imperfect dentinogenesis. Important advances in the biochemical, anatomopathological, genetic, therapeutic and prophylactic fields have resulted in a great present-day interest in this disease. In this work we report six cases of osteogenesis imperfecta according to the current classification and we review the most outstanding aspects.

  10. Study in Mice Links Key Signaling Molecule to Underlying Cause of Osteogenesis Imperfecta

    Science.gov (United States)

    ... on Research Study in Mice Links Key Signaling Molecule to Underlying Cause of Osteogenesis Imperfecta By Kirstie ... a connection between excessive activity of a signaling molecule and osteogenesis imperfecta (OI), a genetic disease characterized ...

  11. Prevalence of Dentinogenesis Imperfecta in a French Population.

    Science.gov (United States)

    Cassia, Antoine; Aoun, Georges; El-Outa, Abbass; Pasquet, Gérard; Cavézian, Robert

    2017-01-01

    Dentinogenesis imperfecta is a genetic disorder of the dentin occurring during the tooth development. It leads to many structural changes that can be identified clinically (brownish colored teeth, cracked enamel) and radiologically (globular crown, cervical constriction, short roots, and obliterated pulp chamber and/or root canals). The aim of this study was to determine by panoramic radiographs assessment the incidence of dentinogenesis imperfecta in a group of patients attending a specialized maxillofacial imaging center in Paris, France. A retrospective observational study was conducted using panoramic radiographs of 8830 patients (3723 males and 5107 females), which were used to search the radiological criteria of dentinogenesis imperfecta. In our sample, the prevalence of dentinogenesis imperfecta was 0.057%. Out of the 8830 subjects, 0.080% of the males presented the radiological signs of the dentinogenesis imperfecta against 0.039% of the females. In our study, we found that dentinogenesis imperfecta is a relatively rare dental anomaly in France, with a rate different from the rates reported in other studies and with no disparity in prevalence among genders.

  12. The Results of the Treatment of Osteogenesis Imperfecta with Corkscrew Tipped Telescopic Nail

    Directory of Open Access Journals (Sweden)

    Hüseyin Günay

    2017-03-01

    Full Text Available Aim: We aimed to evaluate the clinical and radiological results of an intramedullary fixation system used in surgeries for fractures and deformities of osteogenesis imperfecta where we applied a new design corkscrew tipped intramedullary nailing. Materials and Methods: Twenty extremities of 14 osteogenesis cases, who underwent surgery and to whom corkscrew tipped intramedullary treatment was applied, were retrospectively scanned. Ambulation, discrepancies in the lenght of extremities, deformities and joint mobility range were all noted before the operation. Postoperative union rates, complications and our experience regarding the nail were also evaluated. Results: Six tibia and 14 femurs were operated using corkscrew tipped telescopic nails. Two bones were operated due to non-union, while seven bones underwent surgery due to acute fractures and 11 bones due to deformities. All the bones were seen to have achieved the aimed union. No major complications were observed. Infection was present in two cases. Conclusion: Corkscrew tipped telescopic nail is a safe and effective method of fixation in patients with osteogenesis imperfecta.

  13. Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

    Science.gov (United States)

    Oestreich, A K; Carleton, S M; Yao, X; Gentry, B A; Raw, C E; Brown, M; Pfeiffer, F M; Wang, Y; Phillips, C L

    2016-01-01

    Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

  14. Spondylolisthesis caused by extreme pedicle elongation in osteogenesis imperfecta

    Science.gov (United States)

    Fuerderer, Sebastian; Eysel, Peer

    2007-01-01

    Although osteogenesis imperfecta is a well-known skeletal disorder, reports of spondylolisthesis in osteogenesis imperfecta are rare. Only very few cases of spondylolisthesis caused by elongation of lumbar pedicles have been described in the literature. Here we report three patients suffering from osteogenesis imperfecta showing a severe form of hyperlordosis caused by lumbar pedicle elongation and consecutive spondylolisthesis. Radiographs in the course of childhood and adolescence show a rapid progression of pedicle elongation and hyperlordosis with increased mechanical loads. The treatment strategy consists of physiotherapy, medical treatment with bisphosphonates, and orthopedic surgery and is preferably conservative. In the three patients reported here, one patient was treated with laminectomy and postero-lateral fusion, whereas in the other two patients surgery is currently not considered as necessary. PMID:17242874

  15. Dentinogenesis imperfecta: long-term rehabilitation in a child.

    Science.gov (United States)

    Bouvier, Dominique; Leheis, Benoît; Duprez, Jean-Pierre; Bittar, Elias; Coudert, Jean-Loup

    2008-01-01

    The treatment of dentinogenesis imperfecta represents a challenge for the dental practitioner. The aim of this case report was to describe the chronology and problems encountered in the long-term rehabilitation of a young girl suffering from dentinogenesis imperfecta with severe attrition. A 2-stage treatment over a period of 9 years is described and discussed. This treatment comprised an initial treatment to restore esthetic appearance and function during primary and mixed dentitions and a complete prosthetic rehabilitation in a second stage to protect permanent teeth with low-fusion ceramicmetal individual crowns. Discovery of a follicular cyst is also reported and its treatment is described.

  16. Pseudomass of the sternal manubrium in osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Yekeler, Ensar; Kumbasar, Basak; Dursun, Memduh; Tunaci, Mehtap [Department of Radiology, Istanbul University, Istanbul Faculty of Medicine, 34390, Capa, Istanbul (Turkey); Cantez, Serdar; Emiroglu, Halil Haldun [Department of Pediatrics, Istanbul University, Istanbul Faculty of Medicine, 34390, Capa, Istanbul (Turkey)

    2003-06-01

    Skeletal abnormalities such as hypertrophic callus formation and ''popcorn'' calcifications are rare radiological findings of osteogenesis imperfecta, causing tumor-like appearances on imaging. We report on a 7-year-old girl with osteogenesis imperfecta presenting with hepatomegaly and palpable lymphadenopathy in the left inguinal region on physical examination. Computed tomography examination revealed a high-density mass-like lesion of the manubrium sterni. Ultrasonography and a lateral roentgenogram of the chest verified that this was a pseudomass caused by a bowed sternal manubrium. (orig.)

  17. Minimally invasive mitral valve repair in osteogenesis imperfecta.

    Science.gov (United States)

    Tagliasacchi, Isabella; Martinelli, Luigi; Bardaro, Leopoldo; Chierchia, Sergio

    2017-10-01

    Osteogenesis imperfecta is a disorder of the connective tissue that affects several structures including heart valves. However, cardiac surgery is associated with high mortality and morbidity rates. In a 48-year-old man with osteogenesis imperfecta and mitral valve prolapse, we performed the first successful mitral valve repair by right anterior mini-thoracotomy. At the 1-year follow-up, he was asymptomatic and echocardiography confirmed the initial success. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  18. Prenatal diagnosis of lethal osteogenesis imperfecta in twin pregnancy.

    Science.gov (United States)

    Morin, L R; Herlicoviez, M; Loisel, J C; Jacob, B; Feuilly, C; Stanescu, V

    1991-06-01

    Lethal osteogenesis imperfecta was diagnosed at 27 weeks amenorrea in one fetus of a bichorial twin pregnancy. Sonographic findings included: short-limb dwarfism, hypotrophy and hypoechoic bones. The affected fetus was so translucent that only the normal fetus could be seen on plain in utero radiography. The affected fetus died immediately after birth. Postmortem radiography and histology were typical of lethal osteogenesis imperfecta of type IIA. Aids to the etiological diagnosis of in utero dwarfism are presented. Sonographic features correlated with neonatal death are described.

  19. Bulbous epiphysis and popcorn calcification as related to growth plate differentiation in osteogenesis imperfecta

    Science.gov (United States)

    Brizola, Evelise; McCarthy, Edward; Shapiro, Jay Robert

    2015-01-01

    Summary Background Osteogenesis Imperfecta (OI) is an heritable systemic disorder of connective tissue due to different sequence variants in genes affecting both the synthesis of type I collagen and osteoblast function. Dominant and recessive inheritance is recognized. Approximately 90% of the OI cases are due to mutations in COL1A1/A2 genes. We clinically and radiologically describes an adult male with type III osteogenesis imperfecta who presents a rare bone dysplasia termed bulbous epiphyseal deformity in association with popcorn calcifications. Popcorn calcifications may occur with bulbous epiphyseal deformity or independently. Methods Molecular analysis was performed for COL1A1, COL1A2, LEPRE1 and WNT1 genes. Results An uncommon COL1A1 mutation was identified. Clinical and radiological exams confirmed a distinctive bulbous epiphyseal deformity with popcorn calcifications in distal femurs. We have identified four additional OI patients reported in current literature, whose X-rays show bulbous epiphyseal deformity related to mutations in CR-TAP, LEPRE1 and WNT1 genes. Conclusion The mutation identified here had been previously described twice in OI patients and no previous correlation with bulbous epiphyseal deformity was described. The occurrence of this bone dysplasia focuses attention on alterations in normal growth plate differentiation and the subsequent effect on endochondral bone formation in OI. PMID:26604951

  20. Deficient expression of the small proteoglycan decorin in a case of severe/lethal osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Dyne, K.M.; Valli, M.; Forlino, A.; Cetta, G. [Univ. of Pavia (Italy); Mottes, M. [Univ. of Verona (Italy); Kresse, H. [Univ. of Muenster (Germany)

    1996-05-03

    In osteogenesis imperfecta (OI) the effects of mutations in type I collagen genes generally reflect their nature and localization. Unrelated individuals sharing identical mutations present, in general, similar clinical phenotypes. However, in some such cases the clinical phenotype differs. This variable clinical expression could be the result of abnormalities in other connective tissue proteins. Since decorin is a component of connective tissue, binds to type I collagen fibrils and plays a role in matrix assembly, we studied decorin production in skin fibroblasts from OI patients. Cultured fibroblasts from one patient with extremely severe osteogenesis imperfecta (classified as type II/III) who has an {alpha}1(I)gly415ser mutation were found to secrete barely detectable amounts of decorin into culture medium. Western blotting using antibodies raised against decorin confirmed the reduction of the decorin core protein and Northern blot analysis showed decorin mRNA levels below the limit of detection. Cells from a patient, with a less severe phenotype, bearing a mutation in the same position of the triple helix ({alpha}1(1)gly415) expressed decorin normally. The different clinical phenotypes could be due to the differing genetic backgrounds of the patients, so it is tempting to conclude that in our most severely affected patient, the absence of decorin aggravates the clinical phenotype. 34 refs., 4 figs., 1 tab.

  1. Evaluation of stomatognathic problems in children with osteogenesis imperfecta (osteogenesis imperfecta - oi) - preliminary study.

    Science.gov (United States)

    Smoląg, Danuta; Kulesa-Mrowiecka, Małgorzata; Sułko, Jerzy

    2017-01-01

    According to epidemiological data, muscular dysfunctions of the masticatory system occur in 15-23% of the population. Preventive examinations of functional disorders of the stomatognathic system are, therefore, of particular importance. A distinct group of patients exposed to dysfunctions in the area of the masticatory organ locomotor apparatus comprises those with genetic diseases characterised by disorders in collagen formation. One of such diseases is osteogenesis imperfecta (OI) and dentinogenesis imperfecta that usually goes together with the former. The objective of this work was to evaluate the frequency with which particular disorders of the masticatory organ locomotor apparatus occur within the group of patients with osteogenesis imperfecta. The study was performed on patients of the Orthopaedic Clinic of the Polish-American Paediatric Institute in Kraków. The mean age of the children was 7.9 years. In all the cases, a genetic diagnosis of OI has been confirmed. The research methods were based on an in-depth interview on family diseases, pregnancy, postnatal period, feeding, subjective assessment of dysfunctions in the stomatognathic system. An examination of the deformations in the stomatognathic system and the skeleton was conducted, as well as an examination of the trauma and tone of the jaw. The relationship between breastfeeding and swallowing and speech disorders was also evaluated. The impact of intubation on mandibular ranges was investigated. The results obtained were subjected to statistical analysis on the basis of which conclusions were drawn concerning disorders in the stomatognathic system which tend to occur in children with OI. The renunciation of breastfeeding significantly contributes to sucking and swallowing disorders, rumen disorders, as well as biomechanical disorders in the temporomandibular joint. A significant dependence between breastfeeding and swallowing problems was found, whereas there was no such dependence with respect to

  2. Wormian bones in osteogenesis imperfecta and other disorders

    Energy Technology Data Exchange (ETDEWEB)

    Cremin, B.; Goodman, H.; Spranger, J.; Beighton, P.

    1982-03-01

    When are Wormian bones significant is not an easy question to answer, but its relevance is important in relation to bone dysplasias such as osteogenesis imperfecta. Recognition will differ with age of patient, radiographic objectivity, and personal subjectivity. In order to attempt an answer, the skull radiographs of 81 cases of osteogenesis imperfecta of varying ages were examined for the presence of Wormian bones. These were compared against the incidence of Wormian bones in 500 skull radiographs of normal children. Significant Wormian bones as against normal developmental variants were considered to be those more than 10 in number, measuring greater than 6 mm by 4 mm, and arranged in a general mosaic pattern. They were found in all the cases of osteogenesis imperfecta but not in the normal skulls. The occurrence of significant Wormian bones in other bone dysplasias from our material and that of the literature was recorded. Other incidental findings in the skulls of the cases of osteogenesis imperfecta were also appraised.

  3. Collagen-derived markers of bone metabolism in osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Lund, A M; Hansen, M; Kollerup, Gina Birgitte

    1998-01-01

    )] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low...

  4. Complete COL1A1 allele deletions in osteogenesis imperfecta

    NARCIS (Netherlands)

    van Dijk, Fleur S.; Huizer, Margriet; Kariminejad, Ariana; Marcelis, Carlo L.; Plomp, Astrid S.; Terhal, Paulien A.; Meijers-Heijboer, Hanne; Weiss, Marjan M.; van Rijn, Rick R.; Cobben, Jan M.; Pals, Gerard

    2010-01-01

    To identify a molecular genetic cause in patients with a clinical diagnosis of osteogenesis imperfecta (OI) type I/IV. The authors performed multiplex ligation-dependent probe amplification analysis of the COL1A1 gene in a group of 106 index patients. In four families with mild osteogenesis

  5. Mortality and Causes of Death in Patients With Osteogenesis Imperfecta

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Canudas-Romo, Vladimir

    2016-01-01

    Osteogenesis imperfecta (OI) is a hereditary connective tissue disease that causes frequent fractures. Little is known about causes of death and length of survival in OI. The objective of this work was to calculate the risk and cause of death, and the median survival time in patients with OI...

  6. Osteogenesis Imperfecta: Report of Two Consecutive Cases in a ...

    African Journals Online (AJOL)

    Osteogenesis imperfecta is a heritable disorder of connective tissue, affecting both bone and soft tissue. It is characterized by multiple fractures, bone deformities, short stature, ligament laxity, bluish sclera, among others. We present a monogamous family with two affected consecutive siblings, aged 5 and 3 years ...

  7. Forstørret nakkefold kan ses ved osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Schönewolf-Greulich, Bitten; Skibsted, Lillian; Maroun, Lisa Leth

    2011-01-01

    A limited number of reports published since 2001 have described an association between increased nuchal translucency (NT) and osteogenesis imperfecta (OI). We report a new case which underlines the frequency of this association as well as the importance of follow-up and genetic evaluation...

  8. Fracture Rates and Fracture Sites in Patients With Osteogenesis Imperfecta

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Ersbøll, Annette Kjær

    2017-01-01

    Osteogenesis imperfecta (OI) is a hereditary, clinically heterogeneous, connective tissue disorder. The population prevalence of OI in Denmark is 10.6 in 100,000. A hallmark of the disease is frequent fractures that are often precipitated by minimal trauma. The aim of the current study...

  9. Perinatal lethal type II osteogenesis imperfecta: a case report | Ayadi ...

    African Journals Online (AJOL)

    We report a new case of osteogenesis imperfecta (OI) type II which is a perinatal lethal form. First trimester ultrasound didn't identified abnormalities. Second trimester ultrasound showed incurved limbs, narrow chest, with hypomineralization and multiple fractures of ribs and long bones. Parents refused pregnancy ...

  10. [Genetic mutation and clinical features of osteogenesis imperfecta type V].

    Science.gov (United States)

    Guan, Shizhen; Bai, Xue; Wang, Yi; Liu, Zhigang; Ren, Xiuzhi; Zhang, Tianke; Ju, Mingyan; Li, Keqiu; Li, Guang

    2017-12-10

    To explore genetic mutations and clinical features of osteogenesis imperfecta type V. Clinical record of five patients (including one familial case) with osteogenesis imperfecta type V were retrospectively analyzed. Peripheral blood samples of the patients, one family member, as well as healthy controls were collected. Mutation of IFITM5 gene was identified by PCR amplification and Sanger sequencing. A heterozygous mutation (c.-14C>T) in the 5-UTR of the IFITM5 gene was identified in all of the patients and one mother. The clinical findings included frequent fractures and spine and/or extremities deformities, absence of dentinogenesis imperfecta, absence of hearing impairment, and blue sclera in 1 case. Radiographic findings revealed calcification of the interosseous membrane between the radius-ulna in all cases. Hyperplastic callus formation was found in 3 cases. Four had radial-head dislocation. A single heterozygous mutation c.-14C>T was found in the 5-UTR of the IFITM5 gene in 5 patients with osteogensis imperfecta type V. The patients showed specific radiological features including calcification of interosseous membrane, hyperplastic callus formation, and radial-head dislocation.

  11. Osteogenesis Imperfecta in a Young Nigerian Boy | Saleh ...

    African Journals Online (AJOL)

    Osteogenesis imperfecta (OI) is an extremely rare congenital anomaly with similarities to various congenital and acquired musculoskeletal anomalies. Depending on the severity of the disease, presentation can be early or late. The late presentation of this anomaly in a young Nigerian boy whose clinical and radiographic ...

  12. Osteogenesis imperfecta and acute lymphoid leukemia: case report

    Directory of Open Access Journals (Sweden)

    Gabriel David Tarud

    2017-08-01

    Discussion: It is well described that genetic and chromosomal abnormalities increase the risk of leukemia, however the relationship between osteogenesis imperfecta and acute lymphoblastic leukemia is rare. In the world literature, there are few cases mentioning this association. It is important to continue observing the occurrence of later cases, which allow describing if there is a direct relationship between these two entities.

  13. A rare case of Osteogenesis Imperfecta Type III

    Directory of Open Access Journals (Sweden)

    Nagaraj MV, Jehangir HM

    2014-03-01

    Full Text Available Osteogenesis imperfecta (OI the most common genetic cause of osteoporosis is a generalized disorder of connective tissue, characterized by increased bone fragility, low bone mass, recurrent fractures & numerous extra-osseous features with unusual presentations. We report a case of 7 year old female child presenting with respiratory distress with bowing of limb. This case is presented for its rarity.

  14. Complete COL1A1 allele deletions in osteogenesis imperfecta

    NARCIS (Netherlands)

    van Dijk, Fleur S.; Huizer, Margriet; Kariminejad, Ariana; Marcelis, Carlo L.; Plomp, Astrid S.; Terhal, Paulien A.; Meijers-Heijboer, Hanne; Weiss, Marjan M.; van Rijn, Rick R.; Cobben, Jan M.; Pals, Gerard

    2010-01-01

    Purpose: To identify a molecular genetic cause in patients with a clinical diagnosis of osteogenesis imperfecta (OI) type I/IV. Methods: The authors performed multiplex ligation-dependent probe amplification analysis of the COL1A1 gene in a group of 106 index patients. Results: In four families with

  15. Dental occlusion and temporomandibular disorders in adults with osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Gjørup, Hans; Bendixen, Karina Haugaard; Hald, Jannie Dahl

    Osteogenesis imperfecta (OI) is a rare inherited disease characterized by fragile bones because of defective collagen synthesis. OI can be divided into mild OI (Silence type I) and moderate-severe OI (Silence type III-IV). The dental and skeletal aberrations of OI might influence...

  16. Osteogenesis Imperfecta: A Case Report and Review of Literature ...

    African Journals Online (AJOL)

    Osteogenesis imperfecta (OI) is a group of rare inherited disorders of connective tissue with the common feature of excessive fragility of bones caused by mutations in collagen. Diagnosis is mainly based on the clinical features of the disorder. We report, the case of a male neonate delivered to a 33‑year‑old para 2 female at ...

  17. Valvular heart disease in patients with osteogenesis imperfecta.

    Science.gov (United States)

    Najib, Mohammad Q; Schaff, Hartzell V; Ganji, Jhansi; Lee, Howard R; Click, Roger L; Miller, D Craig; Chaliki, Hari P

    2013-03-01

    Osteogenesis imperfecta (OI) or "brittle bone disease" is a rare connective tissue hereditary disorder. The most common clinical presentation of OI is bone fractures. OI also involves extraskeletal structures; however, cardiovascular manifestations are rare. In this report, we describe the cardiovascular anomalies of patients with OI who underwent valve surgery and review the literature on this subject. © 2013 Wiley Periodicals, Inc.

  18. Osteogenesis imperfecta: the audiological phenotype lacks correlation with the genotype.

    NARCIS (Netherlands)

    Swinnen, F.K.R.; Coucke, P.J.; Paepe, A.M. De; Symoens, S.; Malfait, F.; Gentile, F.V.; Sangiorgi, L.; D'Eufemia, P.; Celli, M.; Garretsen, T.J.; Cremers, C.W.R.J.; Dhooge, I.J.; Leenheer, E. de

    2011-01-01

    ABSTRACT: BACKGROUND: Osteogenesis Imperfecta (OI) is a heritable connective tissue disorder mainly caused by mutations in the genes COL1A1 and COL1A2 and is associated with hearing loss in approximately half of the cases. The hearing impairment usually starts between the second and fourth decade of

  19. Temporal bone imaging in osteogenesis imperfecta patients with hearing loss

    NARCIS (Netherlands)

    Swinnen, F.K.R.; Casselman, J.W.; Leenheer, E.M. De; Cremers, C.W.R.J.; Dhooge, I.J.

    2013-01-01

    OBJECTIVES/HYPOTHESIS: Osteogenesis imperfecta (OI) is an autosomal-dominant connective-tissue disorder, predominantly characterized by bone fragility. Conductive hearing loss develops in half of the OI patients and often progresses to mixed loss. Findings of computed tomography (CT) and magnetic

  20. Phlorotannin-incorporated Mesenchymal Stem Cells and their Promising Role in Osteogenesis Imperfecta

    OpenAIRE

    Tehseen Fatima Ali; Tabinda Hasan

    2012-01-01

    Osteogenesis imperfecta as the name suggests, is a bone disorder characterised by imperfect bone mineralisation and development. The key defect lies in the osteoblast–osteoid cycle, leading to insufficient calcification and consequently weak bones. Osteogenesis imperfecta patients are prone to fractures. Till date, numerous growth hormone/synthetic analogues have been used therapeutically in osteogenesis imperfecta patients and they do provide temporary relief, but not without numerous unwant...

  1. Muscle Function in Osteogenesis Imperfecta Type IV.

    Science.gov (United States)

    Veilleux, Louis-Nicolas; Darsaklis, Vasiliki B; Montpetit, Kathleen; Glorieux, Francis H; Rauch, Frank

    2017-10-01

    Results of previous studies suggest that children and adolescents with osteogenesis imperfecta (OI) type IV have muscle force deficits. However, muscle function remains to be objectively quantified in this population. This study aimed to assess upper and lower extremity muscle function in patients with OI type IV. It was carried out in the outpatient department of a pediatric orthopedic hospital; 27 individuals with OI type IV (7-21 years; 13 males), 27 age- and sex-matched individuals with OI type I, and 27 age- and sex-matched controls. Upper extremity muscle force was assessed with hydraulic hand dynamometry, and lower extremity muscle function (peak force per body weight and peak power per body mass) was measured by mechanography through five tests: multiple two-legged hopping, multiple one-legged hopping, single two-legged jump, chair-rise test, and heel-rise test. Upper-limb grip force was normal for patients with OI type IV when compared to height and sex reference data (average z-score = 0.17 ± 1.30; P = 0.88). Compared to age- and sex-matched controls, patients with OI type IV had approximately 30% lower-limb peak force and 50% peak power deficits (P values <0.05). At the lower-limb level, they had a 50% lower peak power than age- and sex-matched patients with OI type I (P < 0.05). Patients with OI type IV have normal upper-limb muscle force but a muscle function deficit at the lower-limb level. These results suggest that lower-limb muscle weakness may contribute to functional deficits in these individuals.

  2. Tratamiento de osteogénesis imperfecta con bisfosfonatos Treatment of osteogenesis imperfecta with bisphosphonates

    Directory of Open Access Journals (Sweden)

    Cristina Tau

    2007-08-01

    Full Text Available El tratamiento con bisfosfonatos (BP, ha mejorado la calidad de vida de los pacientes con osteogénesis imperfecta (OI. Los efectos benéficos son el alivio del dolor, la reducción de la incidencia de fracturas, la mejor movilidad corporal y la recuperación en las formas vertebrales. El tratamiento es más efectivo durante el período de crecimiento. Se presenta una actualización del tema. De la lectura de los anales se destacan los siguientes interrogantes: ¿Por cuánto tiempo deberá instituirse el tratamiento? ¿Es la vía oral tan efectiva como la endovenosa? ¿Cuál es la mejor dosis? ¿Cuándo suspender el tratamiento? ¿Se conservará la integridad del tejido óseo después de un tratamiento prolongado? ¿Qué fenómenos ocurren en el tejido óseo después de la interrupción de la terapia?.Treatment with bisphosphonates (BP improves the quality of life of patients with osteogenesis imperfecta (OI. Beneficial effects are the relief of bone pain, a reduction of fracture incidence, improvement of corporal mobility and recovery of normal vertebral form. Treatment is less effective after completion of growth is here. An update of the literature is here presented. A number of important unsolved questions have been pointed out: for how long should treatment be instituted? Is the oral route as effective as the intravenous one? Which is the best dose? When treatment should be stopped? How well preserved is the longterm integrity of the bones? Which are the phenomena occurring in bone tissue after interruption of therapy?.

  3. Impaired Osteoblastogenesis in a Murine Model of Dominant Osteogenesis Imperfecta: A New Target for Osteogenesis Imperfecta Pharmacological Therapy

    Science.gov (United States)

    Gioia, Roberta; Panaroni, Cristina; Besio, Roberta; Palladini, Giovanni; Merlini, Giampaolo; Giansanti, Vincenzo; Scovassi, Ivana A.; Villani, Simona; Villa, Isabella; Villa, Anna; Vezzoni, Paolo; Tenni, Ruggero; Rossi, Antonio; Marini, Joan C.; Forlino, Antonella

    2012-01-01

    The molecular basis underlying the clinical phenotype in bone diseases is customarily associated with abnormal extracellular matrix structure and/or properties. More recently, cellular malfunction has been identified as a concomitant causative factor and increased attention has focused on stem cells differentiation. Classic osteogenesis imperfecta (OI) is a prototype for heritable bone dysplasias: it has dominant genetic transmission and is caused by mutations in the genes coding for collagen I, the most abundant protein in bone. Using the Brtl mouse, a well-characterized knockin model for moderately severe dominant OI, we demonstrated an impairment in the differentiation of bone marrow progenitor cells toward osteoblasts. In mutant mesenchymal stem cells (MSCs), the expression of early (Runx2 and Sp7) and late (Col1a1 and Ibsp) osteoblastic markers was significantly reduced with respect to wild type (WT). Conversely, mutant MSCs generated more colony-forming unit-adipocytes compared to WT, with more adipocytes per colony, and increased number and size of triglyceride drops per cell. Autophagy upregulation was also demonstrated in mutant adult MSCs differentiating toward osteogenic lineage as consequence of endoplasmic reticulum stress due to mutant collagen retention. Treatment of the Brtl mice with the proteasome inhibitor Bortezomib ameliorated both osteoblast differentiation in vitro and bone properties in vivo as demonstrated by colony-forming unit-osteoblasts assay and peripheral quantitative computed tomography analysis on long bones, respectively. This is the first report of impaired MSC differentiation to osteoblasts in OI, and it identifies a new potential target for the pharmacological treatment of the disorder. PMID:22511244

  4. Children with Osteogenesis Imperfecta and Their Life Situation. Report and Documentation.

    Science.gov (United States)

    Brodin, Jane

    Children with osteogenesis imperfecta form a small and relatively unknown group, with 5 to 10 children diagnosed in Sweden each year and a total of around 200 people under the age of 17 having the condition. A questionnaire was completed by families of 24 Swedish children with osteogenesis imperfecta, and three families were interviewed. The…

  5. Spinal complications in osteogenesis imperfecta: 47 patients 1-16 years of age

    NARCIS (Netherlands)

    Engelbert, R. H.; Gerver, W. J.; Breslau-Siderius, L. J.; van der Graaf, Y.; Pruijs, H. E.; van Doorne, J. M.; Beemer, F. A.; Helders, P. J.

    1998-01-01

    We examined in a cross-sectional study, 47 children (mean age 7.7 (1-16) years) with osteogenesis imperfecta (OI) to find the prevalence of spinal deformities and to correlate these observations with anthropometry. The associations between dentinogenesis imperfecta, joint hypermobility and spinal

  6. Anesthetic Management in a Gravida with Type IV Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Elizabeth Vue

    2016-01-01

    Full Text Available Osteogenesis imperfecta (OI is an inherited disorder of the connective tissues caused by abnormalities in collagen formation. OI may present many challenges to the anesthesiologist. A literature review reveals a wide range of implications, from basic positioning to management of the difficult airway. We present the anesthetic management of a 25-year-old gravid woman with OI, fetal demise, and possible uterine rupture, admitted for an exploratory laparotomy.

  7. A CASE OF OSTEOGENESIS IMPERFECTA WITH S IGNIFICANT DISABILITY

    OpenAIRE

    Sahana; Adarsh; Rajanish; Nirmala; Sreekrishna

    2014-01-01

    Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by structural and quantitative defects in type 1 collagen resulting in susceptibility to fractures of long bones or vertebral compressions from mild or inconsequential trauma 1 .There are different types that range in seve rity from mild form to perinatal lethal form. We present a case of type 3 osteogenesis imperfect with multiple fractures , severe short stature and severe d...

  8. Pamidronate treatment for osteogenesis imperfecta in black South Africans.

    Science.gov (United States)

    Henderson, B D; Isaac, N; Mabele, O; Khiba, S; Nkayi, A; Mokoena, T

    2016-05-25

    Osteogenesis imperfecta is a heritable disorder of bone connective tissue. Type III has a high incidence in the black pop-ulation of South Africa. Affected people experience numerous fractures, bone pain and progressive disability. Until the introduction of bisphosphonates to reduce fracture incidence, treatment revolved around orthopaedic and supportive care. Objective. To assess the subjective attitude of patients towards pamidronate treatment. Thirty black patients with osteogenesis imperfecta type III treated at Universitas Hospital were approached and 26 were included in this study. Patients or their parents were interviewed using a standardised researcher-administered questionnaire, either in person or by telephone. Most patients reported a reduction in symptoms, a feeling of increased wellbeing, increased strength and rated the pamidronate treatment highly. The intravenous route of administration and the side-effects experienced were bearable. Overall all patients would recommend this treatment to other affected persons. This is first study to look at bisphosphonate treatment for osteogenesis imperfecta type III in black South Africans. The treatment is well tolerated and highly rated by the patients. Reported improvements and side-effects are similar to those reported in other populations. Using this form of treatment in this population is supported by these findings.

  9. Severe osteogenesis imperfecta in cyclophilin B-deficient mice.

    Directory of Open Access Journals (Sweden)

    Jae Won Choi

    2009-12-01

    Full Text Available Osteogenesis Imperfecta (OI is a human syndrome characterized by exquisitely fragile bones due to osteoporosis. The majority of autosomal dominant OI cases result from point or splice site mutations in the type I collagen genes, which are thought to lead to aberrant osteoid within developing bones. OI also occurs in humans with homozygous mutations in Prolyl-3-Hydroxylase-1 (LEPRE1. Although P3H1 is known to hydroxylate a single residue (pro-986 in type I collagen chains, it is unclear how this modification acts to facilitate collagen fibril formation. P3H1 exists in a complex with CRTAP and the peptidyl-prolyl isomerase cyclophilin B (CypB, encoded by the Ppib gene. Mutations in CRTAP cause OI in mice and humans, through an unknown mechanism, while the role of CypB in this complex has been a complete mystery. To study the role of mammalian CypB, we generated mice lacking this protein. Early in life, Ppib-/- mice developed kyphosis and severe osteoporosis. Collagen fibrils in Ppib-/- mice had abnormal morphology, further consistent with an OI phenotype. In vitro studies revealed that in CypB-deficient fibroblasts, procollagen did not localize properly to the golgi. We found that levels of P3H1 were substantially reduced in Ppib-/- cells, while CRTAP was unaffected by loss of CypB. Conversely, knockdown of either P3H1 or CRTAP did not affect cellular levels of CypB, but prevented its interaction with collagen in vitro. Furthermore, knockdown of CRTAP also caused depletion of cellular P3H1. Consistent with these changes, post translational prolyl-3-hydroxylation of type I collagen by P3H1 was essentially absent in CypB-deficient cells and tissues from CypB-knockout mice. These data provide significant new mechanistic insight into the pathophysiology of OI and reveal how the members of the P3H1/CRTAP/CypB complex interact to direct proper formation of collagen and bone.

  10. Immunocytochemical Detection of Dentin Matrix Proteins in Primary Teeth from Patients with Dentinogenesis Imperfecta Associated with Osteogenesis Imperfecta

    Science.gov (United States)

    Orsini, G.; Majorana, A.; Mazzoni, A.; Putignano, A.; Falconi, M.; Polimeni, A.; Breschi, L.

    2014-01-01

    Dentinogenesis imperfecta determines structural alterations of the collagen structure still not completely elucidated. Immunohisto-chemical analysis was used to assay type I and VI collagen, various non-collagenous proteins distribution in human primary teeth from healthy patients or from patients affected by type I dentinogenesis imperfecta (DGI-I) associated with osteogenesis imperfecta (OI). In sound primary teeth, an organized well-known ordered pattern of the type I collagen fibrils was found, whereas atypical and disorganized fibrillar structures were observed in dentin of DGI-I affected patients. Expression of type I collagen was observed in both normal and affected primary teeth, although normal dentin stained more uniformly than DGI-I affected dentin. Reactivity of type VI collagen was significantly lower in normal teeth than in dentin from DGI-I affected patients (P<0.05). Expressions of dentin matrix protein-1 (DMP1) and osteopontin (OPN) were observed in both normal dentin and dentin from DGI-I affected patients, without significant differences, being DMP1 generally more abundantly expressed. Immuno labeling for chondroitin sulfate (CS) and biglycan (BGN) was weaker in dentin from DGI-I-affected patients compared to normal dentin, this decrease being significant only for CS. This study shows ultra-structural alterations in dentin obtained from patients affected by DGI-I, supported by immunocytochemical assays of different collagenous and non-collagenous proteins. PMID:25578972

  11. Immunocytochemical detection of dentin matrix proteins in primary teeth from patients with dentinogenesis imperfecta associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    G. Orsini

    2014-10-01

    Full Text Available Dentinogenesis imperfecta determines structural alterations of the collagen structure still not completely elucidated. Immunohistochemical analysis was used to assay Type I and VI collagen, various non-collagenous proteins distribution in human primary teeth from healthy patients or from patients affected by type I dentinogenesis imperfecta (DGI-I associated with osteogenesis imperfecta (OI. In sound primary teeth, an organized well-known ordered pattern of the type I collagen fibrils was found, whereas atypical and disorganized fibrillar structures were observed in dentin of DGI-I affected patients. Expression of type I collagen was observed in both normal and affected primary teeth, although normal dentin stained more uniformly than DGI-I affected dentin. Reactivity of type VI collagen was significantly lower in normal teeth than in dentin from DGI-I affected patients (P<0.05. Expressions of dentin matrix protein (DMP-1 and osteopontin (OPN were observed in both normal dentin and dentin from DGI-I affected patients, without significant differences, being DMP1 generally more abundantly expressed. Immunolabeling for chondroitin sulfate (CS and biglycan (BGN was weaker in dentin from DGI-I-affected patients compared to normal dentin, this decrease being significant only for CS. This study shows ultrastructural alterations in dentin obtained from patients affected by DGI-I, supported by immunocytochemical assays of different collagenous and non-collagenous proteins.

  12. Distinctive tomographic abnormalities of the craniocervical region in a patient with osteogenesis imperfecta type IV B

    Energy Technology Data Exchange (ETDEWEB)

    Kaissi, Ali Al; Klaushofer, Klaus, E-mail: ali.alkaissi@osteologie.a [Ludwig Boltzmann Institute of Osteology, Vienna (Austria); Grill, Franz [Orthopaedic Hospital of Speising, Vienna (Austria). Paediatric Dept.

    2010-07-01

    Osteogenesis imperfecta is a clinically and genetically heterogeneous group of heritable disorders of connective tissue characterized by reduced bone mass (osteopenia) with associated bone fragility. The resulting skeletal manifestations are due to a generalized deficiency in the development of both membranous and endochondral bone and include markedly thin calvarium with delayed closure of the fontanelles and the sutures and excessive Wormian bone formation. Sillence et al. developed a classification system of OI subtypes: OI type I, which is characterised by blue sclerae; perinatal lethal OI type II, also known as congenital OI; OI type III, a progressively deforming subtype with normal sclera; and OI type IV, which is characterized by a normal sclera. Levin et al. have suggested that OI subtypes could be further divided into type A and B based on the absence or presence of dentinogenesis imperfecta. Basilar impression involves the upward (vertical) migration of the odontoid process into the foramen magnum with a depression in the cranium. Basilar impression is a developmental defect and refers to the infolding of the occipital condyles, an elevation of the clivus, and the posterior cranial fossa of the skull. The soft bones of the skull base allow for progressive infolding of the dysplastic clivus and translocation of the odontoid into the posterior fossa. The combination of platybasia and basilar impression can lead to severe distortion of the spinal cord and the anterior brain stem. The specific structures that can be involved include the upper cervical cord, medulla, pons, mid-brain, cerebellum, as well as the vertebrobasilar system. (author)

  13. Phenotypic variability in patients with osteogenesis imperfecta caused by BMP1 mutations.

    Science.gov (United States)

    Pollitt, Rebecca C; Saraff, Vrinda; Dalton, Ann; Webb, Emma A; Shaw, Nick J; Sobey, Glenda J; Mughal, M Zulf; Hobson, Emma; Ali, Farhan; Bishop, Nicholas J; Arundel, Paul; Högler, Wolfgang; Balasubramanian, Meena

    2016-12-01

    Osteogenesis Imperfecta (OI) is an inherited bone fragility disorder most commonly associated with autosomal dominant mutations in the type I collagen genes. Autosomal recessive mutations in a number of genes have also been described, including the BMP1 gene that encodes the mammalian Tolloid (mTLD) and its shorter isoform bone morphogenic protein-1 (BMP1). To date, less than 20 individuals with OI have been identified with BMP1 mutations, with skeletal phenotypes ranging from mild to severe and progressively deforming. In the majority of patients, bone fragility was associated with increased bone mineral density (BMD); however, the full range of phenotypes associated with BMP1 remains unclear. Here, we describe three children with mutations in BMP1 associated with a highly variable phenotype: a sibship homozygous for the c.2188delC mutation that affects only the shorter BMP1 isoform and a further patient who is compound heterozygous for a c.1293C>G nonsense mutation and a c.1148G>A missense mutation in the CUB1 domain. These individuals had recurrent fractures from early childhood, are hypermobile and have no evidence of dentinogenesis imperfecta. The homozygous siblings with OI had normal areal BMD by dual energy X-ray absorptiometry whereas the third patient presented with a high bone mass phenotype. Intravenous bisphosphonate therapy was started in all patients, but discontinued in two patients and reduced in another due to concerns about increasing bone stiffness leading to chalk-stick fractures. Given the association of BMP1-related OI with very high bone material density, concerns remain whether anti-resorptive therapy is indicated in this ultra-rare form of OI.© 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Osteogenesis imperfecta: radiological view on the pediatric patient

    International Nuclear Information System (INIS)

    Siroka, M.; Dovicovicova, A.; Vanatka, R.; Lesny, P.; Bilicky, J.

    2012-01-01

    Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disorder of bone and connective tissue characterized by osteoporosis, fragile bones, hyper extensible joints, dentinogenesis imperfecta, bluish coloration of the sclerae, and adult-onset hearing loss. Detailed medical history, careful physical examination, radiographic features of fractures, and biochemical analysis of skin collagen are the four cornerstones of accurate diagnosis. A radiology specialist should be aware of subtle changes seen on radiographs as well as of specific osteogenesis features (i.e. popcorn calcifications) and difficult differential diagnosis (i.e. hypertrophic callus formation versus osteosarcoma; child abuse fractures versus true osteogenesis imperfecta). About 300 different mutations have been identified within COL1A1 and COL1A2 genes that encode the chains of type I collagen. Depending on the location of the mutation within the collagen gene, these produce a variety of clinical pictures which range from mild OI type I, lethal OI type II to severely deforming OI type III and mildly deforming OI type IV, OI type V is moderate in severity and it is similar to OI type IV, OI type VI is extremely rare and two recessive types of OI, types VII and VIII, were identified in 2006. Each of the eight types has a common radiologic appearance that helps in establishing the diagnosis. The purpose of this article is to give an as comprehensive as possible review of the radiological picture of OI in pediatric patients. Special emphasis will be given to specific radiological prognostic features as well as to the differential diagnosis. (author)

  15. Collagen-derived markers of bone metabolism in osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Lund, A M; Hansen, M; Kollerup, Gina Birgitte

    1998-01-01

    )] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low....... The in vivo findings correlated with in vitro results of collagen I SDS-PAGE. Bone turnover is reduced in OI children and mildly affected OI adults, whereas bone resorption is elevated in severely affected adults. These findings may prove helpful for diagnosis and decision-making regarding therapy in OI....

  16. Clinical perspectives on osteogenesis imperfecta versus non-accidental injury.

    Science.gov (United States)

    Pereira, Elaine Maria

    2015-12-01

    Although non-accidental injuries (NAI) are more common in cases of unexplained fractures than rare disorders such as osteogenesis imperfecta (OI), ruling out OI and other medical causes of fracture is always indicated. The majority of OI patients can be diagnosed with the help of family history, physical examination, and radiographic findings. In particular, there are a few radiological findings which are seen more commonly in NAI than in OI which may help guide clinician considerations regarding the probability of either of these diagnoses. At the same time, molecular testing still merits careful consideration in cases with unexplained fractures without obvious additional signs of abuse. © 2015 Wiley Periodicals, Inc.

  17. Hyperplastic callus formation in osteogenesis imperfecta: CT and MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Rieker, O.; Kreitner, K.F. [Klinik fuer Radiologie, Johannes-Gutenberg-Univ. Mainz (Germany); Karbowski, A. [Orthopaedische Abtl., Krankenhaus der Augustinerinnen, Koeln (Germany)

    1998-09-01

    Hyperplastic callus formation is a noteworthy condition in patients with osteogenesis imperfecta because it often mimicks osteosarcoma on radiography. The findings of CT and MRI in hyperplastic callus formation have not been reported. In the presented case, MRI demonstrated contrast enhancement and edema of the surrounding soft tisssue, consistent with benign as well as malignant disease. Computed tomography showed a calcified rim of the lesion which may be a useful feature to rule out osteosarcoma in this condition. (orig.) With 2 figs., 18 refs.

  18. Perinatal lethal type II osteogenesis imperfecta: a case report.

    Science.gov (United States)

    Ayadi, Imene Dahmane; Hamida, Emira Ben; Rebeh, Rania Ben; Chaouachi, Sihem; Marrakchi, Zahra

    2015-01-01

    We report a new case of osteogenesis imperfecta (OI) type II which is a perinatal lethal form. First trimester ultrasound didn't identified abnormalities. Second trimester ultrasound showed incurved limbs, narrow chest, with hypomineralization and multiple fractures of ribs and long bones. Parents refused pregnancy termination; they felt that the diagnosis was late. At birth, the newborn presented immediate respiratory distress. Postnatal examination and bone radiography confirmed the diagnosis of OI type IIA. Death occurred on day 25 of life related to respiratory failure.

  19. Genotype-Phenotype Correlations in Autosomal Dominant Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    I. Mouna Ben Amor

    2011-01-01

    Full Text Available Osteogenesis imperfecta, discussed in Baldridge et al. 2008 is an inherited bone fragility disorder with a wide range of clinical severity that in the majority of cases is caused by mutations in COL1A1 or COL1A2, the genes that encode the two collagen type I alpha chains. Here we describe genotype-phenotype correlations in OI patients who have mutations affecting collagen type I. This paper is based on findings in a large single-centre OI population and a review of the literature.

  20. MRI-visible pericochlear lesions in osteogenesis imperfecta type I

    Energy Technology Data Exchange (ETDEWEB)

    Ziyeh, S.; Berger, R.; Reisner, K. [Radiologische Klinik, St. Vincentiuskrankenhaeuser, Karlsruhe (Germany)

    2000-10-01

    Osteogenesis imperfecta (OI) is an inherited generalized disorder of type-I collagen synthesis often associated with hearing loss. We present a case of OI type I in which hearing loss led to examination of the temporal bone with MRI. In the osseous otic capsule MRI demonstrated pericochlear lesions with soft tissue signal intensity and contrast enhancement. Changes similar to otosclerosis have been described in the temporal bone of OI patients when applying CT, but reports on MRI findings do not yet exist. (orig.)

  1. Recent developments in osteogenesis imperfecta [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Joseph L. Shaker

    2015-09-01

    Full Text Available Osteogenesis imperfecta (OI is an uncommon genetic bone disease associated with brittle bones and fractures in children and adults. Although OI is most commonly associated with mutations of the genes for type I collagen, many other genes (some associated with type I collagen processing have now been identified. The genetics of OI and advances in our understanding of the biomechanical properties of OI bone are reviewed in this article. Treatment includes physiotherapy, fall prevention, and sometimes orthopedic procedures. In this brief review, we will also discuss current understanding of pharmacologic therapies for treatment of OI.

  2. Clinical Aspects, Imaging Features, and Considerations on Bisphosphonate-Related Osteonecrosis Risk in a Pediatric Patient with Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Fábio Wildson Gurgel Costa

    2014-01-01

    Full Text Available Osteogenesis imperfecta (OI is a rare hereditary condition caused by changes in collagen metabolism. It is classified into four types according to clinical, genetic, and radiological criteria. Clinically, bone fragility, short stature, blue sclerae, and locomotion difficulties may be observed in this disease. OI is often associated to severe dental problems, such as dentinogenesis imperfecta (DI and malocclusions. Radiographically, affected teeth may have crowns with bulbous appearance, accentuated constriction in the cementoenamel junction, narrowed roots, large root canals due to defective dentin formation, and taurodontism (enlarged pulp chambers. There is no definitive cure, but bisphosphonate therapy is reported to improve bone quality; however, there is a potential risk of bisphosphonate-related osteonecrosis of the jaw. In this study we report a case of OI in a male pediatric patient with no family history of OI who was receiving ongoing treatment with intravenous perfusion of bisphosphonate and who required dental surgery. In addition, we discussed the clinical and imaging findings and briefly reviewed the literature.

  3. Osteogenesis imperfecta Type VI with severe bony deformities caused by novel compound heterozygous mutations in SERPINF1.

    Science.gov (United States)

    Cho, Sung Yoon; Ki, Chang-Seok; Sohn, Young Bae; Kim, Su Jin; Maeng, Se Hyun; Jin, Dong-Kyu

    2013-07-01

    Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders characterized by bone fragility, frequent fractures, and low bone mass. Dominantly inherited COL1A1 or COL1A2 mutations appear to be causative in the majority of OI types, but rare recessively inherited genes have also been reported. Recently, SERPINF1 has been reported as another causative gene in OI type VI. To date, only eight SERPINF1 mutations have been reported and all are homozygous. Our patient showed no abnormalities at birth, frequent fractures, osteopenia, and poor response on pamidronate therapy. At the time of her most recent evaluation, she was 8 yr old, and could not walk independently due to frequent lower-extremity fractures, resulting in severe deformity. No clinical signs were seen of hearing impairment, blue sclera, or dentinogenesis imperfecta. In this study, we describe the clinical and radiological findings of one Korean patient with novel compound heterozygous mutations (c.77dupC and c.421dupC) of SERPINF1.

  4. Osteogenesis imperfecta types I-XI: implications for the neonatal nurse.

    Science.gov (United States)

    Womack, Jody

    2014-10-01

    Osteogenesis imperfecta (OI), also called "brittle bone disease," is a rare heterozygous connective tissue disorder that is caused by mutations of genes that affect collagen. Osteogenesis imperfecta is characterized by decreased bone mass, bone fragility, and skin hyperlaxity. The phenotype present is determined according to the mutation on the affected gene as well as the type and location of the mutation. Osteogenesis imperfecta is neither preventable nor treatable. Osteogenesis imperfecta is classified into 11 types to date, on the basis of their clinical symptoms and genetic components. This article discusses the definition of the disease, the classifications on the basis of its clinical features, incidence, etiology, and pathogenesis. In addition, phenotype, natural history, diagnosis and management of this disease, recurrence risk, and, most importantly, the implications for the neonatal nurse and management for the family are discussed.

  5. Basilar impression and osteogenesis imperfecta in a three-year-old girl: CT and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Rush, P.J.; Berbrayer, D.; Reilly, B.J.

    1989-01-01

    A 3-year-old girl with osteogenesis imperfecta developed symptomatic basilar impression. Her neurological symptoms were treated by foramen magnum decompression and laminectomy. This is an unusually young patient to have this condition.

  6. Basilar impression in osteogenesis imperfecta: can it be treated with halo traction and posterior fusion?

    NARCIS (Netherlands)

    Noske, D. P.; van Royen, B. J.; Bron, J. L.; Vandertop, W. P.

    2006-01-01

    Basilar impression (BI) and hydrocephalus complicating osteogenesis imperfecta (OI) is usually treated by anterior transoral decompression and posterior fixation. Nevertheless, it may be questioned if posterior fusion following axial halo traction is adequate in patients with symptomatic BI

  7. Basilar impression and osteogenesis imperfecta in a three-year-old girl: CT and MRI

    International Nuclear Information System (INIS)

    Rush, P.J.; Berbrayer, D.; Reilly, B.J.

    1989-01-01

    A 3-year-old girl with osteogenesis imperfecta developed symptomatic basilar impression. Her neurological symptoms were treated by foramen magnum decompression and laminectomy. This is an unusually young patient to have this condition. (orig.)

  8. OI Issues: Type I - Understanding the Mildest Form of Osteogenesis Imperfecta

    Science.gov (United States)

    ... Flu shots and pneumonia vaccines are often recommended. Social, Emotional, and Family Issues Many people with OI ... Miembro Activo del Equipo de Cuidados de la Salud (FDA) Home Bone Basics Osteoporosis Osteogenesis Imperfecta Paget’s ...

  9. Osteogenesis imperfecta in childhood: impairment and disability--a follow-up study

    NARCIS (Netherlands)

    Engelbert, R. H.; Beemer, F. A.; van der Graaf, Y.; Helders, P. J.

    1999-01-01

    To evaluate differences over time (mean follow-up, 14 months) on impairment parameters (range of joint motion and muscle strength), functional limitation parameters (functional ability), and disability parameters (caregiver assistance in achieving functional skills) in osteogenesis imperfecta (OI),

  10. Osteogenesis imperfecta in childhood: perceived competence in relation to impairment and disability

    NARCIS (Netherlands)

    Engelbert, R. H.; Gulmans, V. A.; Uiterwaal, C. S.; Helders, P. J.

    2001-01-01

    To examine the perceived competence of children with different types of osteogenesis imperfecta (OI) and to investigate the possible relationships between their perceived competence and impairment parameters. Cross-sectional study. National referral center (hospital) for the treatment of children

  11. Evaluation of the severity of malocclusions in children affected by osteogenesis imperfecta with the peer assessment rating and discrepancy indexes.

    Science.gov (United States)

    Rizkallah, Jean; Schwartz, Stephane; Rauch, Frank; Glorieux, Francis; Vu, Duy-Dat; Muller, Katia; Retrouvey, Jean-Marc

    2013-03-01

    Osteogenesis imperfecta is a heritable disorder affecting bone and tooth development. Malocclusion is frequent in those affected by osteogenesis imperfecta, but this has not been studied in detail. The purpose of this study was to describe and quantify the severity of malocclusions in patients with osteogenesis imperfecta. Articulated dental casts were obtained from 49 patients diagnosed with osteogenesis imperfecta (ages 5-19 years; 28 female) and 49 age- and sex-matched control subjects who did not have osteogenesis imperfecta. Both groups were seeking orthodontic treatment. Malocclusions were scored by using the peer assessment rating (PAR) and the discrepancy index (DI). The average United Kingdom weighted PAR scores were 31.1 (SD, 14.5) for the osteogenesis imperfecta group and 22.7 (SD, 10.7) for the control group (P osteogenesis imperfecta and 21.6 (SD, 9.6) for the controls (P osteogenesis imperfecta group and 12.4 (SD, 6.8) for the control group (P osteogenesis imperfecta group, 7.1; control group, 0.3) for the DI parameters and anterior crossbite (osteogenesis imperfecta group, 13.0; control group, 3.8 [United Kingdom]) for the PAR. Both the PAR and the DI showed that malocclusions were significantly more severe in patients with osteogenesis imperfecta than in the control group. There was a higher incidence of Class III malocclusion associated with anterior and lateral open bites in patients affected by osteogenesis imperfecta. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  12. An unusual presentation of osteogenesis imperfecta type I

    Directory of Open Access Journals (Sweden)

    Rebelo M

    2011-04-01

    Full Text Available Marta Rebelo, Jandira Lima, José Diniz Vieira, José Nascimento CostaDepartment of Internal Medicine, University Hospital of Coimbra, Coimbra, PortugalAbstract: Osteogenesis imperfecta (OI is a rare inherited disorder with a broad spectrum of clinical and genetic variability. The genetic diversity involves, in the majority of the cases, mutations in one of the genes that encodes the type 1 collagen protein (COL1 A1 and COL1 A2, but it is not a requirement for the diagnosis. The most benign form is OI type I. The authors present a case report of a 25-year-old woman who had severe low back pain associated with incapacity to walk and breast-feed post-partum. Symptoms developed 2 weeks after delivery. The radiological examination revealed severe osteoporosis with no abnormalities in the laboratory findings. The clinical signs and a positive personal and family history of multiple fractures in childhood suggested OI type I, although other diagnosis, such as pregnancy-associated osteoporosis, was also considered. The atypical presentation of this rare disorder in adulthood calls attention to the need for early diagnosis for prompt treatment. Treatment of OI is never curative, but it improves the quality of the patient’s life.Keywords: osteogenesis imperfecta, collagen, pregnancy, osteoporosis

  13. Advances in the Classification and Treatment of Osteogenesis Imperfecta.

    Science.gov (United States)

    Thomas, Inas H; DiMeglio, Linda A

    2016-02-01

    Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount, structure, or processing. The disease is characterized by an increased susceptibility to bony fracture. In addition to the skeletal phenotype, common additional extraskeletal manifestations include blue sclerae, dentinogenesis imperfecta, vascular fragility, and hearing loss. Medical management is focused on minimizing the morbidity of fractures, pain, and bone deformities by maximizing bone health. Along with optimizing Vitamin D status and calcium intake and physical/occupational therapy, individualized surgical treatment may be indicated. Pharmacological therapy with bisphosphonate medications is now routinely utilized for moderate to severe forms and appears to have a good safety profile and bone health benefits. New therapies with other anti-resorptives as well as anabolic agents and transforming growth factor (TGF)β antibodies are in development. Other potential treatment modalities could include gene therapy or mesenchymal cell transplant. In the future, treatment choices will be further individualized in order to reduce disease morbidity and mortality.

  14. Orthopaedic Considerations for the Adult With Osteogenesis Imperfecta.

    Science.gov (United States)

    Roberts, Timothy T; Cepela, Daniel J; Uhl, Richard L; Lozman, Jeffery

    2016-05-01

    Osteogenesis imperfecta is a heritable group of collagen-related disorders that affects up to 50,000 people in the United States. Although the disease is most symptomatic in childhood, adults with osteogenesis imperfecta also are affected by the sequelae of the disease. Orthopaedic manifestations include posttraumatic and accelerated degenerative joint disease, kyphoscoliosis, and spondylolisthesis. Other manifestations of abnormal collagen include brittle dentition, hearing loss, cardiac valve abnormalities, and basilar invagination. In general, nonsurgical treatment is preferred for management of acute fractures. High rates of malunion, nonunion, and subsequent deformity have been reported with both closed and open treatment. When surgery is necessary, surgeons should opt for load-sharing intramedullary devices that span the entire length of the bone; locking plates and excessively rigid fixation generally should be avoided. Arthroplasty may be considered for active patients, but the procedure frequently is associated with complications in this patient population. Underlying deformities, such as malunion, bowing, rotational malalignment, coxa vara, and acetabular protrusio, pose specific surgical challenges and underscore the importance of preoperative planning.

  15. Osteogenesis Imperfecta in Adult Twins Responded To Treatment With Pamidronate

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    Mehtap Çakır

    2011-06-01

    Full Text Available Bisphosphonates are strong inhibitors of bone resorption and are used in the treatment of osteoporosis. Bisphosphonates are known to be effective in prevention of fractures, improvement of bone mineral density as well as in relieving bone pain in osteogenesis imperfecta (OI patients. Recent studies have shown that especially intravenous pamidronate may be more effective when given in childhood and adolescence. This effect was also shown in adult OI patients in some clinical trials.22-year-old twin brothers known to have OI were admitted to our endocrinology and metabolism outpatient clinic. On medical history, OI was diagnosed at the age of three and for the last eight years, they were not able to walk and were using wheelchairs. On physical examination, blue sclerae and dentinogenesis imperfecta were detected in both patients. According to the expanded Sillence classification of OI, the clinical findings were consistent with type IV OI. Intravenous pamidronate treatment was given three times at four-month intervals, according to Montreal protocol. During this period, the patients were also doing isometric exercises and were on physical therapy, diet, and bioresonance therapy.At the end of one year, bone pain regressed significantly in both patients and they were able to walk independently. These outcomes demonstrate that in selected adult OI patients, intravenous pamidronate treatment may be beneficial in preventing bone fractures and relieving pain. Türk Jem 2011; 15: 39-43

  16. Complete Overlay Denture for Pedodontic Patient with Severe Dentinogenesis Imperfecta.

    Science.gov (United States)

    Syriac, Gibi; Joseph, Elizabeth; Rupesh, Suresh; Mathew, Josey

    2017-01-01

    Dentinogenesis imperfecta (DI) is a hereditary condition that may affect both primary and permanent dentition and is characterized by abnormal dentin formation. The teeth may be discolored with chipping of enamel and, in untreated cases, the entire dentition may wear off to the gingiva. This may lead to the formation of abscesses, tooth mobility, and early loss of teeth. In the Indian population, DI is found to have an incidence of 0.09%. Treatment of DI should aim to remove infection, if any, from the oral cavity; restore form, function, and esthetics; and protect posterior teeth from wear for maintaining the occlusal vertical dimension. Treatment strategies should be selected based on the presenting complaint of the patient, patient's age, and severity of the problem. This case report presents the management of severe DI with tooth worn off until gingival level in a very young patient using complete overlay denture, which has not been reported earlier. How to cite this article: Syriac G, Joseph E, Rupesh S, Mathew J. Complete Overlay Denture for Pedodontic Patient with Severe Dentinogenesis Imperfecta. Int J Clin Pediatr Dent 2017;10(4):394-398.

  17. CLINICAL FEATURES AND PATTERN OF FRACTURES AT THE TIME OF DIAGNOSIS OF OSTEOGENESIS IMPERFECTA IN CHILDREN.

    Science.gov (United States)

    Brizola, Evelise; Zambrano, Marina Bauer; Pinheiro, Bruna de Souza; Vanz, Ana Paula; Félix, Têmis Maria

    2017-01-01

    To characterize the fracture pattern and the clinical history at the time of diagnosis of osteogenesis imperfecta. In this retrospective study, all patients with osteogenesis imperfecta, of both genders, aged 0-18 years, who were treated between 2002 and 2014 were included. Medical records were assessed to collect clinical data, including the presence of blue sclerae, dentinogenesis imperfecta, positive familial history of osteogenesis imperfecta, and the site of the fractures. In addition, radiographic findings at the time of the diagnosis were reviewed. Seventy-six patients (42 females) were included in the study. Individuals' age ranged from 0 to 114 months, with a median (interquartile range) age of 38 (6-96) months. Blue sclerae were present in 93.4% of patients, dentinogenesis imperfecta was observed in 27.6% of patients, and wormian bones in 29.4% of them. The number of fractures at diagnosis ranged from 0 to 17, with a median of 3 (2-8) fractures. Forty (57%) patients had fractures of the upper and lower extremities, and 9 patients also had spinal fractures. The diagnosis was performed at birth in 85.7% of patients with type 3, and 39.3% of those with type 4/5 of the disorder. Osteogenesis imperfecta is a genetic disorder with distinctive clinical features such as bone fragility, recurrent fractures, blue sclerae, and dentinogenesis imperfecta. It is important to know how to identify these characteristics in order to facilitate the diagnosis, optimize the treatment, and differentiate osteogenesis imperfecta from other disorders that also can lead to fractures.

  18. Anesthesia management in a child with osteogenesis imperfecta and epidural hemorrhage.

    Science.gov (United States)

    Erdoğan, Mehmet Ali; Sanli, Mukadder; Ersoy, Mehmet Ozcan

    2013-01-01

    Osteogenesis Imperfecta (OI) results from gene mutation that causes defective or insufficient collagen formation. It may cause various anesthetic complications due to the difficulty in airway management, existence of spinal deformity, respiratory disorders, cardiac anomalies, thrombocyte function disorder, risk of hyperthermia, bacillary invagination, bone deformities and metabolic disorders. The anesthesia management of OI patients should be exercised with caution given certain risks of respiratory disorders. These risks are due to thorax deformity, bone fractures during moving or changing position, mandibular and cervical fractures related with intubation, difficult intubation and malignant hyperthermia. The anesthetic technique using Total Intravenous Anesthesia (TIVA) and laryngeal mask airway is suitable for pediatric patient care with OI. However, these techniques have not yet been reported as useful in neurosurgery case reports. In this study, we present the use of TIVA and ProSeal Laringeal Mask in a child with OI and epidural hemorrhage. We came to the conclusion that LMA and TIVA can safely be used in the anesthetic management of OI patients with severe anesthetic problems. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  19. Potential implications of cell therapy for osteogenesis imperfecta

    Science.gov (United States)

    Niyibizi, Christopher; Li, Feng

    2009-01-01

    Osteogenesis imperfecta (OI) is a brittle-bone disease whose hallmark is bone fragility. Since the disease is genetic, there is currently no available cure. Several pharmacological agents have been tried with not much success, except the recent use of bisphosphonates. Stem cells have been suggested as an alternative OI treatment, but many hurdles remain before this technology can be applied for treating patients with OI. This review summarizes what is known at present regarding the application of stem cells to treat OI using animal models, clinical trials using mesenchymal stem cells to treat patients with OI and the knowledge gained from the clinical trials. Application of gene therapy in combination with stem cells is also discussed. The hurdles to be overcome to bring stem cells close to the clinic and future perspectives are discussed. PMID:20490372

  20. The genetic implication of scoliosis in osteogenesis imperfecta: a review

    Science.gov (United States)

    Liu, Gang; Chen, Jia; Zhou, Yangzhong; Zuo, Yuzhi; Liu, Sen; Chen, Weisheng

    2017-01-01

    Osteogenesis imperfecta (OI) is a kind of heritable connective tissue disorder, including blue sclerae, hearing loss, skeletal dysplasia causing bone fragility and deformities. It is typically caused by collagen related gene mutations, which could lead to bone formation abnormalities. Scoliosis is one of the most common and severe spinal phenotype which has been reported in approximately 26–74.5% of all OI patients. Recent breakthroughs have suggested that OI can be divided into more than 16 types based on genetic mutations with different degrees of scoliosis. In this review, we summarize the etiology of scoliosis in OI, especially the genetic studies of different types. We aim to provide a systematic review of the genetic etiology and clinical suggestions of scoliosis in OI. PMID:29354746

  1. Managing the patient with osteogenesis imperfecta: a multidisciplinary approach

    Science.gov (United States)

    Marr, Caroline; Seasman, Alison; Bishop, Nick

    2017-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous heritable connective tissue disorder characterized by low bone density. The type and severity of OI are variable. The primary manifestations are fractures, bone deformity, and bone pain, resulting in reduced mobility and function to complete everyday tasks. OI affects not only the physical but also the social and emotional well-being of children, young people, and their families. As such, medical, surgical, and allied health professionals’ assessments all play a role in the management of these children. The multidisciplinary approach to the treatment of children and young people living with OI seeks to provide well-coordinated, comprehensive assessments, and interventions that place the child and family at the very center of their care. The coordinated efforts of a multidisciplinary team can support children with OI to fulfill their potential, maximizing function, independence, and well-being. PMID:28435282

  2. Therapy with pamidronate in children with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Marginean O

    2017-08-01

    Full Text Available Otilia Marginean,1 Raluca Corina Tamasanu,1 Niculina Mang,1 Ioana Mozos,2,3 Giorgiana Flavia Brad1 1First Department of Pediatrics, 2Department of Functional Sciences, 3Center for Translational Research and Systems Medicine, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania Abstract: Osteogenesis imperfecta (OI is a genetic disease characterized by excessive bone fragility with fractures consecutive to minor trauma. Considering lack of standardization of therapy with pamidronate in children, it was our aim to present our experience over a period of 10 years regarding evolution and treatment in patients diagnosed with osteoporosis and OI. Nine patients diagnosed with OI were admitted to the First Pediatric Clinic, Timisoara. They were investigated (clinical, biomarkers of bone metabolism and imaging studies, and a quality-of-life questionnaire was used to evaluate the impact of OI. Treatment was performed with pamidronate 1 mg/kg/cycle, every 3 months. The patients were evaluated every 3 months. The most frequent was type III (three patients, and two patients were diagnosed with type II, while the other patients were diagnosed with other forms such as types IV, V, VI and VIII. The clinical expression was polymorphic, and the number of fractures was variable. Bone pain ameliorated just after the first cycle of pamidronate, while the activity and mobility increased quickly. Osteodensitometry in children over 12 years showed a decreased bone mineral density (BMD with a significant improvement after treatment. The values of the bone alkaline phosphatase and osteocalcin changed after the antiresorptive treatment, and the quality of life of the children and their family improved. Treatment with pamidronate is beneficial for the patient, family and society, increases mobility and bone density, improves quality of life and reduces family dependence in children with OI. Keywords: osteoporosis, child, osteogenesis

  3. Initial report of the osteogenesis imperfecta adult natural history initiative.

    Science.gov (United States)

    Tosi, Laura L; Oetgen, Matthew E; Floor, Marianne K; Huber, Mary Beth; Kennelly, Ann M; McCarter, Robert J; Rak, Melanie F; Simmonds, Barbara J; Simpson, Melissa D; Tucker, Carole A; McKiernan, Fergus E

    2015-11-14

    A better understanding of the natural history of osteogenesis imperfecta (OI) in adulthood should improve health care for patients with this rare condition. The Osteogenesis Imperfecta Foundation established the Adult Natural History Initiative (ANHI) in 2010 to give voice to the health concerns of the adult OI community and to begin to address existing knowledge gaps for this condition. Using a web-based platform, 959 adults with self-reported OI, representing a wide range of self-reported disease severity, reported symptoms and health conditions, estimated the impact of these concerns on present and future health-related quality of life (QoL) and completed a Patient-Reported Outcomes Measurement Information System (PROMIS®) survey of health issues. Adults with OI report lower general physical health status (p report generally similar mental health status. Musculoskeletal, auditory, pulmonary, endocrine, and gastrointestinal issues are particular future health-related QoL concerns for these adults. Numerous other statistically significant differences exist among adults with OI as well as between adults with OI and the referent PROMIS® population, but the clinical significance of these differences is uncertain. Adults with OI report lower general health status but are otherwise more similar to the general population than might have been expected. While reassuring, further analysis of the extensive OI-ANHI databank should help identify areas of unique clinical concern and for future research. The OI-ANHI survey experience supports an internet-based strategy for successful patient-centered outcomes research in rare disease populations.

  4. Impact of three genetic musculoskeletal diseases: a comparative synthesis of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

    Science.gov (United States)

    Dogba, Maman Joyce; Rauch, Frank; Douglas, Erin; Bedos, Christophe

    2014-10-25

    Achondroplasia, Duchenne muscular dystrophy, and osteogenesis imperfecta are among the most frequent rare genetic disorders affecting the musculoskeletal system in children. Rare genetic disorders are severely disabling and can have substantial impacts on families, children, and on healthcare systems. This literature review aims to classify, summarize and compare these non-medical impacts of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

  5. Impact of three genetic musculoskeletal diseases: a comparative synthesis of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta

    OpenAIRE

    Dogba, Maman Joyce; Rauch, Frank; Douglas, Erin; Bedos, Christophe

    2014-01-01

    Achondroplasia, Duchenne muscular dystrophy, and osteogenesis imperfecta are among the most frequent rare genetic disorders affecting the musculoskeletal system in children. Rare genetic disorders are severely disabling and can have substantial impacts on families, children, and on healthcare systems. This literature review aims to classify, summarize and compare these non-medical impacts of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

  6. Asymptomatic parental mosaicism for osteogenesis imperfecta associated with a new splice site mutation in COL1A2

    OpenAIRE

    Frederiksen, Anja Lisbeth; Duno, Morten; Johnsen, Iben B. G.; Nielsen, Morten Frost; Kr?ig?rd, Anne Bruun

    2016-01-01

    Key Clinical Message Recurrent lethal perinatal osteogenesis imperfecta may result from asymptomatic parental mosaicism. A previously unreported mutation in COL1A2 leads to recurrent cases of fetal osteogenesis imperfecta Sillence type IIA, which emphasizes the importance of clinical and genetic evaluation of mosaicism in asymptomatic parents as verified mosaicism highly increases recurrence risk.

  7. Osteogénesis imperfecta en una gatita de 2 meses - Osteogenesis imperfect in a kitten 2 months

    OpenAIRE

    Rodríguez, O; Turco, V; Vilar, JM; Morales M; Miró, F; Martinez, A

    2012-01-01

    ResumenLa ostegénesis imperfecta es una enfermedad congénita. Normalmente es causada por un gen que produce el colágeno tipo I, fundamental para el desarrollo del hueso.SummaryOsteogenesis imperfecta is a congenital disorder. It is normally caused by the gene that produces type I collagen, which is responsible for bone formation.

  8. Severe osteogenesis imperfecta Type-III and its challenging treatment in newborn and preschool children. A systematic review.

    Science.gov (United States)

    Sinikumpu, Juha-Jaakko; Ojaniemi, Marja; Lehenkari, Petri; Serlo, Willy

    2015-08-01

    Osteogenesis imperfecta (OI) is a group of genetic disorders, of which Type III is the most severe among survivors. The disease is characterised in particular by bone fragility, decreased bone mass and increased incidence of fractures. Other usual findings are muscle hypotonia, joint hypermobility and short stature. Fractures and weak bones may consequently cause limb and spinal deformity and chronic physical disability. Bisphosphonates have revolutionised the treatment of newborn children with severe OI type III. Surgery is still needed in most patients due to high frequency of the fractures. In this systematic review we describe the present state-of-art in treating the most severe type of OI in newborn and preschool children with their bone fractures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Radiation therapy of hyperplastic heterotopic ossifications in osteogenesis imperfecta; Two case reports. Strahlentherapie hyperplastischer heterotoper Ossifikationen bei Osteogenesis imperfecta; Zwei Falldarstellungen

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    Micke, O. (Muenster Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie - Radioonkologie); Wagner, W. (Muenster Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie - Radioonkologie); Poetter, R. (Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria). Universitaetsklinik fuer Strahlentherapie und Strahlenbiologie); Prott, F.J. (Muenster Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie - Radioonkologie); Karbowski, A. (Muenster Univ. (Germany). Klinik und Poliklinik fuer Allgemeine Orthopaedie)

    1994-06-01

    Purpose: Osteogenesis imperfecta is a rare hereditary disease of connective tissue with a genetic defect in collagen synthesis. In osteogenesis imperfecta hyperplastic heterotopic ossification can be induced by hyperplastic callus formation caused by trauma or operation. Heterotopic ossifications can be found in numerous benign diseases. The successful use of low dose radiotherapy in the treatment of heterotopic ossifications in well-known from the literature. Patients and Methods: We treated two children (a 13-year old girl and a ten-year old boy) with heterotopic ossifications of the lower extremities in osteogenesis imperfecta type IV (Lobstein) with a low dose irradiation (10x1 Gy, respectively 6x1 Gy) under megavoltage conditions. Results: After radiotherapy the children were painfree and the hyperplastic callus was considerably reduced. The previously immobilized patients could partly be mobilized. Thereby it could be contributed to the rehabilitation of the patients. New hyperplastic callus formation was not observed in the irradiated areas so far. Conclusion: Analogous to the successful radiation of heterotopic ossifications in other benign diseases radiation therapy seems to be a successful treatment of hyperplastic callus formation in osteogenesis imperfecta. Despite the late risks of radiotherapy radiation treatment of benign diseases in children might be indicated. (orig.)

  10. COL1A2 gene analysis in a Czech osteogenesis imperfecta patient: a candidate novel mutation in a patient affected by osteogenesis imperfecta type 3

    Directory of Open Access Journals (Sweden)

    Hrušková L

    2015-08-01

    Full Text Available Lucie Hrušková,1 Ivo Mařík,2,3 Stella Mazurová,1 Pavel Martásek,1 Ivan Mazura1 1Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 2Ambulant Centre for Defects of Locomotor Apparatus 1.1.c., Prague, Czech Republic; 3Faculty of Medical Studies, West Bohemia University, Pilsen, Czech RepublicAbstract: Osteogenesis imperfecta is a heritable bone fragility disease with a heterogenic genetic origin. Most cases result from mutations of either the COL1A1 gene or the COL1A2 gene. We identified a novel COL1A2 gene mutation in a Czech patient, born to unaffected parents, who was diagnosed according to clinical and anthropometric findings and radiographic features as having type 3 osteogenesis imperfecta, which is a severe form of this disease. The identified Gly814Trp mutation was predicted by a number of complementary bioinformatic programs to result in functional alteration of the protein. This case report provides both evidence of a novel COL1A2 mutation resulting in type 3 osteogenesis imperfecta and a genotype:phenotype correlation in this affected individual. Keywords: osteogenesis imperfecta type 3, collagen, alpha-2 (I chain, substitution, sequencing 

  11. Quantitative second-harmonic generation imaging to detect osteogenesis imperfecta in human skin samples

    Science.gov (United States)

    Adur, J.; Ferreira, A. E.; D'Souza-Li, L.; Pelegati, V. B.; de Thomaz, A. A.; Almeida, D. B.; Baratti, M. O.; Carvalho, H. F.; Cesar, C. L.

    2012-03-01

    Osteogenesis Imperfecta (OI) is a genetic disorder that leads to bone fractures due to mutations in the Col1A1 or Col1A2 genes that affect the primary structure of the collagen I chain with the ultimate outcome in collagen I fibrils that are either reduced in quantity or abnormally organized in the whole body. A quick test screening of the patients would largely reduce the sample number to be studied by the time consuming molecular genetics techniques. For this reason an assessment of the human skin collagen structure by Second Harmonic Generation (SHG) can be used as a screening technique to speed up the correlation of genetics/phenotype/OI types understanding. In the present work we have used quantitative second harmonic generation (SHG) imaging microscopy to investigate the collagen matrix organization of the OI human skin samples comparing with normal control patients. By comparing fibril collagen distribution and spatial organization, we calculated the anisotropy and texture patterns of this structural protein. The analysis of the anisotropy was performed by means of the two-dimensional Discrete Fourier Transform and image pattern analysis with Gray-Level Co-occurrence Matrix (GLCM). From these results, we show that statistically different results are obtained for the normal and disease states of OI.

  12. [Postoperative radiation therapy for a patient with osteogenesis imperfecta: case report].

    Science.gov (United States)

    Ducournau, A; Lagarde, P; Henriques de Figueiredo, B; Antoine, M; Breton-Callu, C; Petit, A; Dallaudière, B; Sargos, P

    2014-03-01

    Osteogenesis imperfecta is an unusual disease also called Lobstein disease. Characterized by abnormalities of collagen biosynthesis, a possible mutation on 17th chromosome is described. On the other hand, 29% of breast cancers present a mutation on the same chromosome. Nevertheless, the association of osteogenesis imperfecta and breast cancer is at the moment unknown. Therapeutic management is very difficult because of a loss in dihydropyrimidine dehydrogenase for patients having osteogenesis imperfecta, generating some toxicity by default in catabolism of 5-fluorouracil. We report the case of a 49-year-old woman with a breast cancer in the context of osteogenesis imperfecta. Dosimetric considerations permitting to reduce chess dose level have been performed for this patient. With a follow-up of 6 months, no imaging fracture has been revealed after radiotherapy. No evident conclusion about radiation injury from a case report could be described in case of osteogenesis imperfecta. To our knowledge, this is the first case which take into account potential radiation induced toxicities. Copyright © 2014. Published by Elsevier SAS.

  13. Transcatheter mitral valve repair in osteogenesis imperfecta associated mitral valve regurgitation.

    Science.gov (United States)

    van der Kley, Frank; Delgado, Victoria; Ajmone Marsan, Nina; Schalij, Martin J

    2014-08-01

    Osteogenesis imperfecta is associated with increased prevalence of significant mitral valve regurgitation. Surgical mitral valve repair and replacement are feasible but are associated with increased risk of bleeding and dehiscence of implanted valves may occur more frequently. The present case report describes the outcomes of transcatheter mitral valve repair in a patient with osteogenesis imperfecta. A 60 year-old patient with osteogenesis imperfecta and associated symptomatic moderate to severe mitral regurgitation underwent transthoracic echocardiography which showed a nondilated left ventricle with preserved systolic function and moderate to severe mitral regurgitation. On transoesophageal echocardiography the regurgitant jet originated between the anterolateral scallops of the anterior and posterior leaflets (A1-P1). Considering the comorbidities associated with osteogenesis imperfecta the patient was accepted for transcatheter mitral valve repair using the Mitraclip device (Abbott vascular, Menlo, CA). Under fluoroscopy and 3D transoesophageal echocardiography guidance, a Mitraclip device was implanted between the anterolateral and central scallops with significant reduction of mitral regurgitation. The postoperative evolution was uneventful. At one month follow-up, transthoracic echocardiography showed a stable position of the Mitraclip device with no mitral regurgitation. Transcatheter mitral valve repair is feasible and safe in patients with osteogenesis imperfecta and associated symptomatic significant mitral regurgitation. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  14. Successful anterior cruciate ligament reconstruction and meniscal repair in osteogenesis imperfecta.

    Science.gov (United States)

    Park, Jae-Young; Cho, Tae-Joon; Lee, Myung Chul; Han, Hyuk-Soo

    2018-03-20

    A case of anterior cruciate ligament (ACL) reconstruction with meniscal repair in an osteogenesis imperfecta patient is reported. A 24-year-old female with osteogenesis imperfecta type 1a suffered from a valgus extension injury resulting in tear of ACL and medial meniscus. She underwent an arthroscopic-assisted ACL reconstruction and medial meniscus repair. Meniscal tear at the menisco-capsular junction of the posterior horn of medial meniscus was repaired with three absorbable sutures via inside-out technique. ACL reconstruction was then performed with a bone-patellar tendon-bone allograft. The patient was followed up for 1 year with intact ACL grafts and healed medial meniscus. This case report showed that successful ACL reconstruction and meniscal repair is possible in an osteogenesis imperfecta patient.Level of evidence V.

  15. Clinical application of antenatal genetic diagnosis of osteogenesis imperfecta type IV.

    Science.gov (United States)

    Yuan, Jing; Li, Song; Xu, YeYe; Cong, Lin

    2015-04-02

    Clinical analysis and genetic testing of a family with osteogenesis imperfecta type IV were conducted, aiming to discuss antenatal genetic diagnosis of osteogenesis imperfecta type IV. Preliminary genotyping was performed based on clinical characteristics of the family members and then high-throughput sequencing was applied to rapidly and accurately detect the changes in candidate genes. Genetic testing of the III5 fetus and other family members revealed missense mutation in c.2746G>A, pGly916Arg in COL1A2 gene coding region and missense and synonymous mutation in COL1A1 gene coding region. Application of antenatal genetic diagnosis provides fast and accurate genetic counseling and eugenics suggestions for patients with osteogenesis imperfecta type IV and their families.

  16. Successful bone-anchored hearing aid implantation in a patient with osteogenesis imperfecta.

    Science.gov (United States)

    Coutinho, M B; Marques, C; Mendes, G J; Gonçalves, C

    2015-11-01

    To report a case of successful bone-anchored hearing aid implantation in an adult patient with type III osteogenesis imperfecta, which is commonly regarded as a contraindication to this procedure. A 45-year-old man with type III osteogenesis imperfecta presented with mixed hearing loss. There was a mild sensorineural component in both ears, with an air-bone gap between 45 and 50 dB HL. He was implanted with a bone-anchored hearing aid. The audiological outcome was good, with no complications and good implant stability (as measured by resonance frequency analysis). To our knowledge, this is the first recorded case of bone-anchored hearing aid implantation in a patient with osteogenesis imperfecta.

  17. Custom hemiarthroplasties for retention of existing hardware associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Kevin Nishida, MS

    2017-06-01

    Full Text Available Osteogenesis imperfecta is a rare genetic disorder that presents with heterogeneous phenotypes ranging from brittle bones to impaired hearing. Because of the decreased bone mineral density frequently observed in this patient population, many patients experience recurring and long-term fractures, which often require orthopaedic management. With the advancement of nonsurgical and surgical management and increased longevity of patients with osteogenesis imperfecta, the incidence of osteoarthritis has risen, presenting new orthopaedic challenges. However, compromised bone integrity and size combined with frequent existing hardware render traditional surgical therapies for osteoarthritis technically challenging in this patient population. In this report, we present a case in which we retained a portion of the patient's existing hardware, while performing staged bilateral custom hemiarthroplasties in a patient with osteogenesis imperfecta.

  18. Bent Telescopic Rods in Patients With Osteogenesis Imperfecta.

    Science.gov (United States)

    Lee, R Jay; Paloski, Michael D; Sponseller, Paul D; Leet, Arabella I

    2016-09-01

    Telescopic rods require alignment of 2 rods to enable lengthening. A telescopic rod converts functionally into a solid rod if either rod bends, preventing proper engagement. Our goal was to characterize implant bending as a mode of failure of telescopic rods used in the treatment of osteogenesis imperfecta in children. We conducted a retrospective review of our osteogenesis imperfecta database for patients treated with intramedullary telescopic rods at our institution from 1992 through 2010 and identified 12 patients with bent rods. The 6 boys and 6 girls had an average age at the time of initial surgery of 3.1 years (range, 1.8 to 8.3 y) and a total of 51 telescoping rods. Clinic notes, operative reports, and radiographs were reviewed. The rods were analyzed for amount of lengthening, characteristics of bending, presence of cut out, or disengagement from an anchor point. Bends in the rods were characterized by their location on the implant component. The bent and straight rods were compared. Data were analyzed with the Mann-Whitney test (statistical significance set at P≤0.05). Of the 51 telescoping rods, 17 constructs (33%) bent. The average interval between surgery and rod bending was 4.0 years (range, 0.9 to 8.2 y). Before bending, 11 of 17 telescoping rods had routine follow-up radiographs for review. In 10 of the rods, bending was present when early signs of rod failure were first detected. Rod bending did not seem to be related to rod size. There was no area on the rod itself that seemed more susceptible to bending. Rod bending can be an early sign of impending rod failure. When rod bending is first noted, it may predispose the rod to other subsequent failures such as loss of proximal and distal fixation and cut out. Rod bending should be viewed as an indicator for closer monitoring of the patient and discussions regarding future need for rod exchange. Level III-retrospective review.

  19. Evaluation of teriparatide treatment in adults with osteogenesis imperfecta

    Science.gov (United States)

    Orwoll, Eric S.; Shapiro, Jay; Veith, Sandra; Wang, Ying; Lapidus, Jodi; Vanek, Chaim; Reeder, Jan L.; Keaveny, Tony M.; Lee, David C.; Mullins, Mary A.; Nagamani, Sandesh C.S.; Lee, Brendan

    2014-01-01

    Background. Adults with osteogenesis imperfecta (OI) have a high risk of fracture. Currently, few treatment options are available, and bone anabolic therapies have not been tested in clinical trials for OI treatment. Methods. 79 adults with OI were randomized to receive 20 μg recombinant human parathyroid hormone (teriparatide) or placebo for 18 months in a double-blind, placebo-controlled trial. The primary endpoint was the percent change in areal bone mineral density (aBMD) of the lumbar spine (LS), as determined by dual-energy X-ray absorptiometry. Secondary endpoints included percent change in bone remodeling markers and vertebral volumetric BMD (vBMD) by quantitative computed tomography, estimated vertebral strength by finite element analysis, and self-reported fractures. Results. Compared with the placebo group, the teriparatide group showed increased LS aBMD (6.1% ± 1.0% vs. 2.8% ± 1.0% change from baseline; P teriparatide therapy (18% ± 6% and 15% ± 3% change, respectively), but declined with placebo (–5.0% ± 6% and –2.0% ± 3% change; P teriparatide therapy (135% ± 14% and 64% ± 10% change, respectively). Teriparatide-induced elevation of P1NP levels was less pronounced in severe forms of OI (type III/IV) compared with the milder form (type I). Type I OI patients exhibited robust BMD increases with teriparatide; however, there was no observed benefit for those with type III/IV OI. There was no difference in self-reported fractures between the 2 groups. Conclusions. Adults with OI, particularly those with less severe disease (type I), displayed a teriparatide-induced anabolic response, as well as increased hip and spine aBMD, vertebral vBMD, and estimated vertebral strength. Trial registration. Clinicaltrials.gov NCT00131469. Funding. The Osteoporosis Imperfecta Foundation, Eli Lilly and Co., the National Center for Advancing Translational Science (NCATS) at the NIH (grant no. UL1RR024140), and the Baylor College of Medicine General Clinical

  20. [Oral cavity features in patients suffering from osteogenesis imperfecta].

    Science.gov (United States)

    Alania, K N; Iverieli, M B; Abashidze, N O; Gogishvili, Kh B; Chigladze, T T

    2011-04-01

    Osteogenesis Imperfecta (OI) is a rare hereditary connective tissue disorder. This pathology is characterized by disruption of biosynthesis of Type I collagen, and production of limited amount of defective and imperfect collagens. This causes decrease in bone mass of human body, bones become fragile and brittle, resulting in unreasonable multiple fractures. Reportedly, number of patients with OI ranges between 32-38 in Georgia. However, exact number of patients, including children and their parents, is unknown. Dentinogenesis Imperfecta (DI; DGI) and skeletal malocclusion occupy special place in varied spectrum of OI clinical symptoms. We studied 14 patients: 9 women (64.3%), 5 men (35.7%) and divided them in three age groups: I - 2.5-6 years - period of primary dentition (28.6%), II - 6-14 years - period of changing teeth dentition (35.7%) and III - above 14 years - period of permanent dentition (35.7%). 28.5% of screened patients had one of the symptoms of DI, such as tooth discoloration. Discoloration of primary teeth was revealed in 4 patients (primary dentition). Another symptom of DI, such as early abrasion, was detected in 5 patients i.e. 35.71%. This was divided in the following manner: I age group - 3 cases, II and III age groups - 1-1 cases. It was also observed that early abrasion of primary teeth prevails over permanent. One of DI's radiographic symptoms, such as peculiar form of teeth crown and root, was revealed in 21.4% or in 3 patients, 2 of whom had bulbous crown, and the third one deformed (curved) root. Peculiar characteristics of DI, such as increased constriction of the coronal-radicular junction, obliterated pulp chamber, short and narrow roots, were not observed in the patients examined. Interesting characteristic of DI, such as periapical destruction of intact tooth root, was revealed in the form of bone defect in 7.1% of those examined (1 patient). Therefore, out of examined 14 patients with OI - DI had 6 patients or 42.85% of cases. Also

  1. Second-trimester diagnosis of osteogenesis imperfecta associated with schizencephaly by sonography

    International Nuclear Information System (INIS)

    Ozkur, A.; Kervancioglu, R.; Kervancioglu, S.; Bayram, M.; Dikensoy, E.

    2007-01-01

    Osteogenesis imperfecta is congenital connective tissue disorder characterized with multiple bone fractures, short limbs, membranous calvarium with wormian bones and sometimes blue sclerae. Osteogenesis is rarely accompanied by other major malformations. Although associations with microcephaly congenital heart defects or anencephaly have been reported previously, association with schizencephaly was not found on literature review. We report a case of osteogenesis imperfecta associated with schizencephaly diagnosed at 21 weeks of gestation using 2-dimensional ultrasound. The present case shows that prenatal ultrasonographic examination is a very important tool to detect such intrauterine abnormalities in which, management of pregnancy would be changed significantly compared to normal pregnancies. (author)

  2. Anestesia venosa total em paciente portador de Osteogênesis imperfecta: relato de caso Anestesia venosa total en paciente portador de Osteogénesis imperfecta: relato de caso Total intravenous anesthesia in Osteogenesis imperfecta patient: case report

    Directory of Open Access Journals (Sweden)

    José Francisco Nunes Pereira das Neves

    2004-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A Osteogênesis Imperfecta é uma doença genética rara do tecido conjuntivo, com prevalência de 1/10000, que primariamente envolve a ossificação endocondral, resultando em ossos frágeis, múltiplas fraturas e deformidades esqueléticas. O objetivo desse artigo foi relatar um caso de paciente portador de Osteogenesis Imperfecta, submetido à anestesia venosa total para tratamento cirúrgico de fratura de fêmur. RELATO DO CASO: Paciente do sexo masculino, 15 anos, 41 kg, 140 cm, com história de Osteogênesis Imperfecta e cardiopatia, programado para tratamento cirúrgico de fratura do fêmur. Na sala de operação foi monitorizado com ECG, FC, PANI e SpO2 e submetido à anestesia geral venosa total com propofol, alfentanil e cisatracúrio. Após IOT, foi acrescentada monitorização da P ET CO2 e da temperatura esofágica. No período intra-operatório e na sala de recuperação pós-anestésica não apresentou complicações. Teve alta hospitalar no 5º dia de pós-operatório. CONCLUSÕES: O presente relato mostrou boa evolução intra e pós-operatória de paciente com Osteogênesis Imperfecta submetido à anestesia geral venosa total. A complexidade da doença mostrou a necessidade de avaliação e monitorização adequada pelo anestesiologista.JUSTIFICATIVA Y OBJETIVOS: La Osteogénesis Imperfecta es una rara enfermedad genética del tejido conjuntivo, con prevalencia de 1/10000, que primariamente envuelve la osificación endocondral, resultando en huesos frágiles, múltiplas fracturas e deformidades esqueléticas. El objetivo de ese artículo fue relatar un caso de paciente portador de Osteogénesis Imperfecta, sometido a anestesia venosa total para tratamiento quirúrgico de fractura de fémur. RELATO DEL CASO: Paciente del sexo masculino, 15 años, 41 kg, 140 cm, con historia de Osteogénesis Imperfecta y cardiopatía, programado para tratamiento quirúrgico de fractura del fémur. En la sala de operaci

  3. Osteogenesis imperfecta at the beginning of bone and joint decade.

    Science.gov (United States)

    Primorac, D; Rowe, D W; Mottes, M; Barisić, I; Anticević, D; Mirandola, S; Gomez Lira, M; Kalajzić, I; Kusec, V; Glorieux, F H

    2001-08-01

    Osteogenesis imperfecta (OI), or brittle bone disease, is a heritable disorder characterized by increased bone fragility. Four different types of the disease are commonly distinguished, ranging from a mild condition (type I) to a lethal one (type II). Types III and IV are the severe forms surviving the neonatal period. In most cases, there is a reduction in the production of normal type I collagen or the synthesis of abnormal collagen as a result of mutations in the type I collagen genes. These classic forms of OI are described in this review. There are instances, however, where alterations in bone matrix components, other than type I collagen, are the basic abnormalities of the OI. Recently, three such discrete types have been identified by histomorphometric evaluation (types V and VI) and linkage analysis (Rhizomelic OI). They provide evidence for the as yet poorly understood complexity of the phenotype-genotype correlation in OI. We also discuss bisphosphonates treatment as well as fracture management and surgical correction of deformities observed in the patients with OI. However, ultimately, strengthening bone in OI will involve steps to correct the underlying genetic mutations that are responsible for this disorder. Thus, we also describe different genetic therapeutic approaches that have been tested either on OI cells or on available OI murine models.

  4. Current and emerging treatments for the management of osteogenesis imperfecta

    Science.gov (United States)

    Monti, Elena; Mottes, Monica; Fraschini, Paolo; Brunelli, PierCarlo; Forlino, Antonella; Venturi, Giacomo; Doro, Francesco; Perlini, Silvia; Cavarzere, Paolo; Antoniazzi, Franco

    2010-01-01

    Osteogenesis imperfecta (OI) is the most common bone genetic disorder and it is characterized by bone brittleness and various degrees of growth disorder. Clinical severity varies widely; nowadays eight types are distinguished and two new forms have been recently described although not yet classified. The approach to such a variable and heterogeneous disease should be global and therefore multidisciplinary. For simplicity, the objectives of treatment can be reduced to three typical situations: the lethal perinatal form (type II), in which the problem is survival at birth; the severe and moderate forms (types III–IX), in which the objective is ‘autonomy’; and the mild form (type I), in which the aim is to reach ‘normal life’. Three types of treatment are available: non-surgical management (physical therapy, rehabilitation, bracing and splinting), surgical management (intramedullary rod positioning, spinal and basilar impression surgery) and medical-pharmacological management (drugs to increase the strength of bone and decrease the number of fractures as bisphosphonates or growth hormone, depending on the type of OI). Suggestions and guidelines for a therapeutic approach are indicated and updated with the most recent findings in OI diagnosis and treatment. PMID:20856683

  5. Managing the patient with osteogenesis imperfecta: a multidisciplinary approach

    Directory of Open Access Journals (Sweden)

    Marr C

    2017-04-01

    Full Text Available Caroline Marr,1,* Alison Seasman,1,* Nick Bishop2 1Metabolic Bone Disease Team, 2Academic Unit of Child Health, Department of Human Metabolism, University of Sheffield, Sheffield Children’s NHS Foundation Trust, Sheffield, UK *These authors contributed equally to this work Abstract: Osteogenesis imperfecta (OI is a heterogeneous heritable connective tissue disorder characterized by low bone density. The type and severity of OI are variable. The primary manifestations are fractures, bone deformity, and bone pain, resulting in reduced mobility and function to complete everyday tasks. OI affects not only the physical but also the social and emotional well-being of children, young people, and their families. As such, medical, surgical, and allied health professionals’ assessments all play a role in the management of these children. The multidisciplinary approach to the treatment of children and young people living with OI seeks to provide well-coordinated, comprehensive assessments, and interventions that place the child and family at the very center of their care. The coordinated efforts of a multidisciplinary team can support children with OI to fulfill their potential, maximizing function, independence, and well-being. Keywords: physical therapy, occupational therapy, bisphosphonates, nursing, psychology, pediatrics

  6. Osteogenesis Imperfecta Type VI in Individuals from Northern Canada.

    Science.gov (United States)

    Ward, Leanne; Bardai, Ghalib; Moffatt, Pierre; Al-Jallad, Hadil; Trejo, Pamela; Glorieux, Francis H; Rauch, Frank

    2016-06-01

    Osteogenesis imperfecta (OI) type VI is a recessively inherited form of OI that is caused by mutations in SERPINF1, the gene coding for pigment-epithelium derived factor (PEDF). Here, we report on two apparently unrelated children with OI type VI who had the same unusual homozygous variant in intron 6 of SERPINF1 (c.787-10C>G). This variant created a novel splice site that led to the in-frame addition of three amino acids to PEDF (p.Lys262_Ile263insLeuSerGln). Western blotting showed that skin fibroblasts with this mutation produced PEDF but failed to secrete it. Both children were treated with intravenous bisphosphonates, but the treatment of Individual 1 was switched to subcutaneous injections of denosumab (dose 1 mg per kg body weight, repeated every 3 months). An iliac bone sample obtained after 5 denosumab injections (and 3 months after the last injection) showed no change in the increased osteoid parameters that are typical of OI type VI, but the number of osteoclasts in trabecular bone was markedly increased. This suggests that the effect of denosumab on osteoclast suppression is of shorter duration in children with OI type VI than what has previously been reported on adults with osteoporosis.

  7. Physiotherapy and patients with osteogenesis imperfecta: an experience report

    Directory of Open Access Journals (Sweden)

    Carmem Lia Martins Moreira

    Full Text Available Introduction Individuals with osteogenesis imperfecta (OI have bone fragility and osteopenia which cause fractures, mobility restriction and pain. Objective This article examines a physiotherapy experience with people diagnosed with OI in an OI reference center of Rio de Janeiro. Materials and methods This was an exploratory qualitative study, based on field notes related to physiotherapy care to 92 patients of both genders with clinical diagnoses of OI, aged between 30 days and 37 years old, during the period 2004–2008. The analysis comprised a reading of the field notes as a corpus, considering them as a means of understanding the subjects’ perspectives. Two different forms of codification were applied — open and focused — followed by semiotic analysis techniques. Results Early encouragement to perform active movements within a safe environment, or even after fractures, reduced articular contractures and enhanced muscular tonus; physiotherapy manipulation facilitated the integration of body perception in relation to movements and responses to tactile-kinesthetic-vestibular stimuli; promoting family involvement, by adopting practical solutions adapted to each patient’s reality, contributed to reduce fear of fractures and allowed the construction of a new functional image. Conclusion Physiotherapy assessment and treatment should be based not only on clinical and neurofunctional elements and technical strategies, but also on a dialogue that includes the multiple dimensions of the patients and their family members, in order to engage them in a learning process to stimulate potentials, abilities and competences.

  8. Recessive Osteogenesis Imperfecta Caused by Missense Mutations in SPARC

    Science.gov (United States)

    Mendoza-Londono, Roberto; Fahiminiya, Somayyeh; Majewski, Jacek; Tétreault, Martine; Nadaf, Javad; Kannu, Peter; Sochett, Etienne; Howard, Andrew; Stimec, Jennifer; Dupuis, Lucie; Roschger, Paul; Klaushofer, Klaus; Palomo, Telma; Ouellet, Jean; Al-Jallad, Hadil; Mort, John S.; Moffatt, Pierre; Boudko, Sergei; Bächinger, Hans-Peter; Rauch, Frank

    2015-01-01

    Secreted protein, acidic, cysteine-rich (SPARC) is a glycoprotein that binds to collagen type I and other proteins in the extracellular matrix. Using whole-exome sequencing to identify the molecular defect in two unrelated girls with severe bone fragility and a clinical diagnosis of osteogenesis imperfecta type IV, we identified two homozygous variants in SPARC (GenBank: NM_003118.3; c.497G>A [p.Arg166His] in individual 1; c.787G>A [p.Glu263Lys] in individual 2). Published modeling and site-directed mutagenesis studies had previously shown that the residues substituted by these mutations form an intramolecular salt bridge in SPARC and are essential for the binding of SPARC to collagen type I. The amount of SPARC secreted by skin fibroblasts was reduced in individual 1 but appeared normal in individual 2. The migration of collagen type I alpha chains produced by these fibroblasts was mildly delayed on SDS-PAGE gel, suggesting some overmodification of collagen during triple helical formation. Pulse-chase experiments showed that collagen type I secretion was mildly delayed in skin fibroblasts from both individuals. Analysis of an iliac bone sample from individual 2 showed that trabecular bone was hypermineralized on the material level. In conclusion, these observations show that homozygous mutations in SPARC can give rise to severe bone fragility in humans. PMID:26027498

  9. Dentinogenesis imperfecta type II: approach for dental treatment

    Directory of Open Access Journals (Sweden)

    Raquel Mantuaneli Scarel-Caminaga

    Full Text Available INTRODUCTION: Dentinogenesis imperfecta (DI is a hereditary dentin development disorder that affects both primary and permanent dentitions. The DI characteristics are discolored and translucent teeth ranging from gray to brownish-blue or amber. The enamel may split readily from the dentin when subjected to occlusal stress. Radiographically there are evident of cervical constrictions, short root and pulp chambers, and the root canals are smaller than normal or completely obliterated. The dental treatment choice can be decided on a case-by case‑basis, considering the degree of dental tissue loss, and child age and cooperation. OBJECTIVE: The aim of this case report was to describe the early dental treatment performed in a child affected by DI type II. CASE REPORT: The treatment involved basic preventive procedures. Primary molars were worn to such an extent that the remained tooth structure was covered with composite resin to protect the exposed dentin. Resin-based sealant was applied in all first permanent molars. Posterior cross bite was treated with the expansion of the upper arch. CONCLUSION: The early treatment restored the patient´s vertical dimension resulting in acceptable esthetics and function for the permanent teeth to complete their eruption.

  10. Prosthetic treatment in dentinogenesis imperfecta type II: a case report

    Directory of Open Access Journals (Sweden)

    Sedat Güven

    2016-05-01

    Full Text Available INTRODUCTION: Dentinogenesis imperfecta (DI or hereditary opalescent dentin is an autosomal dominant disorder affecting both primary and permanent dentition. Early diagnosis and treatment of DI is important for normal facial growth and esthetic continuity by preserving occlusion and tooth structure. It also provides psychological motivation by increasing the patient’s quality of life. Providing functional dentition in DI patients prevents loss of the vertical dimension, while enabling normal growth of the facial bones and jaw joint. CASE REPORT: A 20-year-old male with DI was referred to our clinic with chewing difficulty and esthetic and speech problems. His brother also had this disease. Oral examination showed the loss of many teeth and the absence of enamel on most of the remaining teeth, causing discoloration and exposing soft dentinal tissue with calcification disorder. Despite widespread attrition of the teeth, pulp chambers were not exposed. The tip of the lower jaw was prominent in the patient’s profile. Placing metal-ceramic fixed dentures in the lower jaw and an overdenture prosthesis in the upper jaw improved the patient’s psychological state as well as his function, phonation, and esthetics. CONCLUSION: This case report presents the intraoral findings in a patient with DI, including the histopathological findings, and the prosthetic treatment approach and the treatment outcome.

  11. Childhood Osteoporosis and Presentation of Two Cases with Osteogenesis Imperfecta Type V / Osteoporoza V Otroški Dobi in Predstavitev Dveh Bolnikov Z Osteogenesis Imperfecta Tipa V

    Directory of Open Access Journals (Sweden)

    Bratanic Nina

    2015-03-01

    Full Text Available Uvod. Osteogenesis imperfecta (OI je vzročno heterogena bolezen, katere značilnost je osteoporoza v otroštvu. Pri vseh opisanih bolnikih s podtipom OI tipa V je vzrok bolezni ista mutacija c.-14C>T gena IFITM5. Kljub temu med bolniki obstaja izrazita fenotipska variabilnost v klinični sliki, toda opisan je le dober odgovor na zdravljenje z bisfosfonati.

  12. Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta

    NARCIS (Netherlands)

    Becker, J.; Semler, O.; Gilissen, C.F.H.A.; Li, Y.; Bolz, H.J.; Giunta, C.; Bergmann, C.; Rohrbach, M.; Koerber, F.; Zimmermann, K.; Vries, P.F. de; Wirth, B.; Schoenau, E.; Wollnik, B.; Veltman, J.A.; Hoischen, A.; Netzer, C.

    2011-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous genetic disorder characterized by bone fragility and susceptibility to fractures after minimal trauma. After mutations in all known OI genes had been excluded by Sanger sequencing, we applied next-generation sequencing to analyze the exome of a single

  13. Osteogenesis imperfecta: recent findings shed new light on this once well-understood condition.

    Science.gov (United States)

    Basel, Donald; Steiner, Robert D

    2009-06-01

    Osteogenesis imperfecta is a systemic heritable disorder of connective tissue whose cardinal manifestation is bone fragility. In approximately 90% of individuals with osteogenesis imperfecta, mutations in either of the genes encoding the pro-alpha1 or pro-alpha2 chains of type I collagen (COL1A1 or COL1A2) can be identified. Of those without collagen mutations, a number of them will have mutations involving the enzyme complex responsible for posttranslational hydroxylation of the position 3 proline residue of COL1A1. Two of the genes encoding proteins involved in that enzyme complex, LEPRE1 and cartilage-associated protein, when mutated have been shown to cause autosomal recessive osteogenesis imperfecta, which has a moderate to severe clinical phenotype, often indistinguishable from osteogenesis imperfecta types II or III. Mutations in COL1A1 or COL1A2 which result in an abnormal protein still capable of forming a triple helix cause a more severe phenotype than mutations that lead to decreased collagen production as a result of the dominant negative effect mediated by continuous protein turnover. The current standard of care includes a multidisciplinary approach with surgical intervention when necessary, proactive physiotherapy, and consideration for the use of bisphosphonates all in attempts to improve quality of life.

  14. Children with Osteogenesis Imperfecta and Their Daily Living. Handicap Research Group Report No. 4.

    Science.gov (United States)

    Brodin, Jane

    The study examined aspects of daily living of Swedish children with osteogenesis imperfecta, a mineral deficiency in the skeleton which results in stunted growth and frequent fractures. A questionnaire was administered to 24 families with children under the age of 18 and 3 families were interviewed. The study found the families in great need of…

  15. Three Preschool Children with Osteogenesis Imperfecta--Interviews with Parents. Handicap Research Group Report No. 5.

    Science.gov (United States)

    Brodin, Jane; Millde, Kristina

    The report describes three preschool Swedish children with osteogenesis imperfecta (brittle bones) and the psychosocial support families require from society. Introductory sections explain the condition, review international research on brittle bones, consider the life situation of children with brittle bones, and examine societal support for…

  16. Intramedullary rodding in type III osteogenesis imperfecta. Effects on neuromotor development in 10 children

    NARCIS (Netherlands)

    Engelbert, R. H.; Helders, P. J.; Keessen, W.; Pruijs, H. E.; Gooskens, R. H.

    1995-01-01

    We studied retrospectively gross motor development and the impact of intramedullary rodding in 10 children with type III osteogenesis imperfecta (OI). There was a pronounced delay in motor development and the order in achieving gross motor milestones differed from the normal developmental sequence.

  17. Osteogenesis imperfecta : profiles of motor development as assessed by a postal questionnaire

    NARCIS (Netherlands)

    Engelbert, RHH; Uiterwaal, CSPM; Gulmans, VAM; Pruijs, HEH; Helders, PJM

    This study was performed to achieve more detailed information regarding the age and sequence in the development of motor milestones in the different types of osteogenesis imperfecta (OI). The parents of 98 patients with a diagnosis of OI were sent a questionnaire regarding the age at which patients

  18. Percutaneous vertebroplasty in the treatment of vertebral body compression fracture secondary to osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Rami, Parag M.; Heatwole, Eric V.; Boorstein, Jeffrey M. [Center for Vascular and Interventional Radiology, St. Vincent Mercy Medical Center, Toledo, OH (United States); McGraw, Kevin J. [Riverside Methodist Hospital, Columbus, OH (United States)

    2002-03-01

    Percutaneous vertebroplasty, a minimally invasive interventional radiological procedure, has recently been used effectively for the treatment of symptomatic vertebral body compression fractures. Primary indications for vertebroplasty include osteoporotic compression fracture, osteolytic vertebral metastasis and myeloma, and vertebral hemangioma. We present a case and extend the indication of percutaneous vertebroplasty in a patient with a vertebral body compression fracture secondary to osteogenesis imperfecta. (orig.)

  19. MRI and CT features of hyperplastic callus in osteogenesis imperfecta tarda

    Energy Technology Data Exchange (ETDEWEB)

    Dobrocky, I. [Diagnostic Center Meidling, Vienna (Austria); Seidl, G. [Diagnostic Center Meidling, Vienna (Austria)]|[Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria); Grill, F. [Orthopaedisches Spital Wien Speising, Vienna (Austria)

    1999-05-01

    We describe the MRI and CT findings of hyperplastic callus formation simulating a tumour of pelvis in patient with osteogenesis imperfecta tarda. Possible differential diagnoses and the impact of different imaging techniques on the correct diagnosis are discussed. (orig.) With 3 figs., 5 refs.

  20. Atypical femoral fracture in an osteogenesis imperfecta patient successfully treated with teriparatide

    DEFF Research Database (Denmark)

    Holm, Jakob; Eiken, Pia; Hyldstrup, Lars

    2014-01-01

    OBJECTIVE: We report a case of a successfully healed atypical femoral fracture (AFF) following treatment with teriparatide in a patient with osteogenesis imperfecta (OI). To our knowledge, no successful treatment of AFFs with teriparatide in this subpopulation has ever been described. METHODS...

  1. Osteogenesis imperfecta in childhood: impairment and disability. A prospective study with 4-year follow-up

    NARCIS (Netherlands)

    Engelbert, Raoul H.; Uiterwaal, Cuno S.; Gerver, Willem-Jan; van der Net, Jan-Jaap; Pruijs, Hans E.; Helders, Paul J.

    2004-01-01

    To study (1). changes in anthropometrics, joint range of motion (ROM), muscle strength, functional ability, caregiver assistance, and level of ambulation in children with osteogenesis imperfecta (OI) and (2). the prediction of clinical characteristics at the level of ambulation at follow-up and the

  2. A case of osteogenesis imperfecta type II, a diagnosis made almost ...

    African Journals Online (AJOL)

    Background: Osteogenesis imperfecta (OI) is a rare autosomal dominant disorder of type I collagen (COL I), characterised by excessive bone fragility with low bone mineral density (BMD). Type II is associated with extreme bone fragility leading to intrauterine or early infant death. Objective: To highlight a case of OI type II ...

  3. Cardiopulmonary fitness and muscle strength in patients with osteogenesis imperfecta type I

    NARCIS (Netherlands)

    Takken, Tim; Terlingen, Heike C.; Helders, Paul J. M.; Pruijs, Hans; van der Ent, Cornelis K.; Engelbert, Raoul H. H.

    2004-01-01

    To evaluate cardiopulmonary function, muscle strength, and cardiopulmonary fitness (VO 2 peak) in patients with osteogenesis imperfecta (OI). In 17 patients with OI type I (mean age 13.3 +/- 3.9 years) cardiopulmonary function was assessed at rest using spirometry, plethysmography,

  4. Osteogenesis imperfecta: profiles of motor development as assessed by a postal questionnaire

    NARCIS (Netherlands)

    Engelbert, R. H.; Uiterwaal, C. S.; Gulmans, V. A.; Pruijs, H. E.; Helders, P. J.

    2000-01-01

    This study was performed to achieve more detailed information regarding the age and sequence in the development of motor milestones in the different types of osteogenesis imperfecta (OI). The parents of 98 patients with a diagnosis of OI were sent a questionnaire regarding the age at which patients

  5. Efficacy and safety of bisphosponate therapy in children with osteogenesis imperfecta: a systematic review

    NARCIS (Netherlands)

    Rijks, Ester B G; Bongers, B.C.; Vlemmix, MJG; Boot, A.M.; van Dijk, ATH; Sakkers, RJB; van Brussel, M

    2015-01-01

    Background/Aims: To systematically assess contemporary knowledge regarding the effectiveness and safety of bisphosphonates (BPs) in children with osteogenesis imperfecta (OI). Methods: PubMed/MEDLINE, Embase, and Cochrane were searched for eligible articles up to June 2014. Studies eligible for

  6. Targeting the LRP5 pathway improves bone properties in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Jacobsen, Christina M; Barber, Lauren A; Ayturk, Ugur M; Roberts, Heather J; Deal, Lauren E; Schwartz, Marissa A; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

    2014-10-01

    The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5(p.A214V) ) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5(+/p.A214V) mice to Col1a2(+/p.G610C) mice, which model human type IV OI. We found that Col1a2(+/p.G610C) ;Lrp5(+/p.A214V) offspring had significantly increased bone mass and strength compared to Col1a2(+/p.G610C) ;Lrp5(+/+) littermates. The improved bone properties were not a result of altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2(+/p.G610C) mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody-treated mice had significantly increased bone mass and strength compared to vehicle-treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI. © 2014 American Society for Bone and Mineral Research.

  7. Efficacy of Denosumab for Osteoporosis in Three Female Patients with Osteogenesis Imperfecta.

    Science.gov (United States)

    Uehara, Masashi; Nakamura, Yukio; Takahashi, Jun; Kamimura, Mikio; Ikegami, Shota; Suzuki, Takako; Uchiyama, Shigeharu; Yamaguchi, Tomomi; Kosho, Tomoki; Kato, Hiroyuki

    2017-06-01

    Osteogenesis imperfecta (OI) is an inherited bone disorder that causes fractures due to impaired production of collagen type I. In recent years, denosumab, a human monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), has become widely used as an anti-osteoclastic agent for osteoporosis. This study investigated osteoporotic cases of OI to examine effects of denosumab on bone fragility. This was a retrospective, consecutive case series that included 3 female patients aged 42, 40, and 14 years, respectively. One patient carries a point mutation (c.G769A) in the COL1A1 gene, encoding collagen type I alpha 1 chain, which causes an amino-acid substitution (p.G257R). By contrast, no mutation was found in the analyzed regions of the OI responsive genes in another two patients (mother and daughter). These three patients underwent subcutaneous injection of denosumab every 6 months. All patients underwent dual-energy X-ray absorptiometry for bone mineral density (BMD) measurement of the lumbar 1-4 spine (L-BMD) and bilateral hips (H-BMD) before and during treatment. BMD and laboratory data were evaluated before, between 2 and 4 months, and at 6, 12, 18, and 24 months of therapy. No fractures or severe side effects, such as hypocalcemia, were observed during denosumab treatment. Both L-BMD and H-BMD were increased by denosumab. At 24 months, the mean percentage changes in L-BMD and H-BMD were 14.7% and 15.1%, respectively. In conclusion, no bone fragility fractures occurred during 2 years of denosumab administration in OI patients. Denosumab therefore is a good therapeutic option in the OI patients.

  8. Osteogenesis imperfecta and primary open angle glaucoma: genotypic analysis of a new phenotypic association.

    Science.gov (United States)

    Wallace, Dana J; Chau, Felix Y; Santiago-Turla, Cecilia; Hauser, Michael; Challa, Pratap; Lee, Paul P; Herndon, Leon W; Allingham, R Rand

    2014-01-01

    Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by bone fragility. Ocular findings include blue sclera, low ocular rigidity, and thin corneal thickness. However, there are no documented cases linking OI and primary open angle glaucoma (POAG). In this report, we describe three individuals, one isolated case and two from a multiplex family, with OI type I and POAG. Available family members with OI and POAG had a complete eye examination, including visual acuity, intraocular pressure (IOP), pachymetry, slit-lamp exam, dilated fundus exam, and visual fields. DNA from blood samples was sequenced and screened for mutations in COL1A1/2 and myocilin (MYOC). All subjects had OI type I. Findings of POAG included elevated IOP, normal gonioscopy, and glaucomatous optic disc cupping and visual field loss. POAG cosegregated with OI in the multiplex family. The multiplex family had a single nucleotide insertion (c.540_541insC) in COL1A1 resulting in a frameshift mutation and a premature termination codon. The sporadic case had a COL1A1 splice acceptor site mutation (c.2452-2A>T or IVS36-2A>T) predicted to result in a premature termination codon due to intron inclusion or a cryptic splice site. None of the glaucoma cases had mutations or sequence changes in MYOC. We identified two novel mutations in COL1A1 in individuals with OI type I and POAG. Thus, some mutations in COL1A1 may be causative for OI and POAG. Alternatively, susceptibility genes may interact with mutations in COL1A1 to cause POAG.

  9. Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Orioli, I.M. [Universidade Federal do Rio de Janeiro (Brazil); Castilla, E.E. [Centro de Educacion Medica e Investigacion Clinica, Buenos Aires (Argentina); Scarano, G.; Mastroiacovo, P. [Universita Cattolica, Rome (Italy)

    1995-11-06

    The paternal ages of nonfamilial cases of achondroplasia (AC) (n = 78), thanatophoric dysplasia (TD) (n = 64), and osteogenesis imperfecta (OI) (n = 106), were compared with those of matched controls, from an Italian Indagine Policentrica Italiana sulle Malformazioni Congenite (IPIMC) and a South American Estudio Colaborativo Latinoamericano de Malformaciones Congenitas (ECLAMC) series. The degree of paternal age effect on the origin of these dominant mutations differed among the three conditions. Mean paternal age was highly elevated in AC, 36.30 {plus_minus} 6.74 years in the IPIMC, and 37.19 {plus_minus} 10.53 years in the ECLAMC; less consistently elevated in TD, 33.60 {plus_minus} 7.08 years in the IPIMC, and 36.41 {plus_minus} 9.38 years in the ECLAMC; and only slightly elevated in OI in the ECLAMC, 31.15 {plus_minus} 9.25 years, but not in the IPIMC, 32.26 {plus_minus} 6.07 years. Increased maternal age or birth order in these conditions disappeared when corrected for paternal age. Approximately 50% of AC and TD cases, and only 30% of OI cases, were born to fathers above age 35 years. For AC and TD, the increase in relative incidence with paternal age fitted an exponential curve. The variability of paternal age effect in these new mutations could be due, among other reasons, to the high proportion of germ-line mosaicism in OI parents, or to the localization of the AC gene, mapped to the 4p16.3 region, in the neighborhood of an unstable DNA area. 28 refs., 1 fig., 6 tabs.

  10. Developmental charts for children with osteogenesis imperfecta, type I (body height, body weight and BMI).

    Science.gov (United States)

    Graff, Krzysztof; Syczewska, Malgorzata

    2017-03-01

    Osteogenesis imperfecta (OI) is a rare genetic disorder of type I collagen. Type I is the most common, which is called a non-deforming type of OI, as in this condition, there are no major bone deformities. This type is characterised by blue sclera and vertebral fractures, leading to mild scoliosis. The body height of these patients is regarded as normal, or only slightly reduced, but there are no data proving this in the literature. The aim of this study is the preparation of the developmental charts of children with OI type I. The anthropometric data of 117 patients with osteogenesis imperfecta were used in this study (61 boys and 56 girls). All measurements were pooled together into one database (823 measurements in total). To overcome the problem of the limited number of data being available in certain age classes and gender groups, the method called reverse transformation was used. The body height of the youngest children, aged 2 and 3 years, is less than that of their healthy peers. Children between 4 and 7 years old catch up slightly, but at later ages, development slows down, and in adults, the median body height shows an SDS of -2.7. These results show that children with type I OI are smaller from the beginning than their healthy counterparts, their development slows down from 8 years old, and, ultimately, their body height is impaired. What is Known: • The body height of patients with osteogenesis imperfecta type I is regarded as normal, or only slightly reduced, but in the known literature, there is no measurement data supporting this opinion. What is New: • Children with type I osteogenesis imperfecta are smaller from the beginning than their healthy counterparts, their development slows down from 8 years old and, ultimately, their final body height is impaired. • The developmental charts for the body height, body weight and BMI of children with type I osteogenesis imperfecta are shown.

  11. Pamidronate Affects the Mandibular Cortex of Children with Osteogenesis Imperfecta

    Science.gov (United States)

    Apolinário, A.C.; Figueiredo, P.T.; Guimarães, A.T.; Acevedo, A.C.; Castro, L.C.; Paula, A.P.; Paula, L.M.; Melo, N.S.; Leite, A.F.

    2015-01-01

    We hypothesized that mandibular cortical width (MCW) is smaller in children with osteogenesis imperfecta (OI) than in healthy children and that pamidronate can improve the cortical mandibular thickness. The aim of this study was to assess changes in the MCW on dental panoramic radiographs (DPRs) of children with normal bone mineral density (BMD) and with OI. We also compared the MCW of children with different types of OI regarding the number of pamidronate cycles and age at the beginning of treatment. MCW measurements were retrospectively obtained from 197 DPRs of 66 children with OI types I, III, and IV who were in treatment with a comparable dosage of cyclical intravenous pamidronate between 2007 and 2013. The control group had 92 DPRs from normal BMD children. Factorial analysis of variance was used to compare MCW measurements among different age groups and between sexes and also to compare MCW measurements of children with different types of OI among different pamidronate cycles and age at the beginning of treatment. No significant differences in results were found between male and female subjects in both OI and healthy children, so they were evaluated altogether (P > 0.05). There was an increase of MCW values related to aging in all normal BMD and OI children but on a smaller scale in children with OI types I and III. Children with OI presented lower mean MCW values than did children with normal BMD at the beginning of treatment (P < 0.05). A linear model estimated the number of pamidronate cycles necessary to achieve mean MCW values equivalent to those of healthy children. The thinning of the mandibular cortex depended on the number of pamidronate cycles, the type of OI, and the age at the beginning of treatment. DPRs could thus provide a way to identify cyclic pamidronate treatment outcomes in patients with OI. PMID:25608973

  12. Metabolic phenotype in the mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Boraschi-Diaz, Iris; Tauer, Josephine T; El-Rifai, Omar; Guillemette, Delphine; Lefebvre, Geneviève; Rauch, Frank; Ferron, Mathieu; Komarova, Svetlana V

    2017-09-01

    Osteogenesis imperfecta (OI) is the most common heritable bone fragility disorder, usually caused by dominant mutations in genes coding for collagen type I alpha chains, COL1A1 or COL1A2 Osteocalcin (OCN) is now recognized as a bone-derived regulator of insulin secretion and sensitivity and glucose homeostasis. Since OI is associated with increased rates of bone formation and resorption, we hypothesized that the levels of undercarboxylated OCN are increased in OI. The objective of this study was to determine changes in OCN and to elucidate the metabolic phenotype in the Col1a1 Jrt/+ mouse, a model of dominant OI caused by a Col1a1 mutation. Circulating levels of undercarboxylated OCN were higher in 4-week-old OI mice and normal by 8 weeks of age. Young OI animals exhibited a sex-dependent metabolic phenotype, including increased insulin levels in males, improved glucose tolerance in females, lower levels of random glucose and low adiposity in both sexes. The rates of O 2 consumption and CO 2 production, as well as energy expenditure assessed using indirect calorimetry were significantly increased in OI animals of both sexes, whereas respiratory exchange ratio was significantly higher in OI males only. Although OI mice have significant physical impairment that may contribute to metabolic differences, we specifically accounted for movement and compared OI and WT animals during the periods of similar activity levels. Taken together, our data strongly suggest that OI animals have alterations in whole body energy metabolism that are consistent with the action of undercarboxylated osteocalcin. © 2017 Society for Endocrinology.

  13. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment.

    Science.gov (United States)

    Van Dijk, F S; Sillence, D O

    2014-06-01

    Recently, the genetic heterogeneity in osteogenesis imperfecta (OI), proposed in 1979 by Sillence et al., has been confirmed with molecular genetic studies. At present, 17 genetic causes of OI and closely related disorders have been identified and it is expected that more will follow. Unlike most reviews that have been published in the last decade on the genetic causes and biochemical processes leading to OI, this review focuses on the clinical classification of OI and elaborates on the newly proposed OI classification from 2010, which returned to a descriptive and numerical grouping of five OI syndromic groups. The new OI nomenclature and the pre-and postnatal severity assessment introduced in this review, emphasize the importance of phenotyping in order to diagnose, classify, and assess severity of OI. This will provide patients and their families with insight into the probable course of the disorder and it will allow physicians to evaluate the effect of therapy. A careful clinical description in combination with knowledge of the specific molecular genetic cause is the starting point for development and assessment of therapy in patients with heritable disorders including OI. © 2014 The Authors. American Journal of Medical Genetics Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2014 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

  14. What is new in genetics and osteogenesis imperfecta classification?

    Directory of Open Access Journals (Sweden)

    Eugênia R. Valadares

    2014-12-01

    Full Text Available OBJECTIVE: Literature review of new genes related to osteogenesis imperfecta (OI and update of its classification. SOURCES: Literature review in the PubMed and OMIM databases, followed by selection of relevant references. SUMMARY OF THE FINDINGS: In 1979, Sillence et al. developed a classification of OI subtypes based on clinical features and disease severity: OI type I, mild, common, with blue sclera; OI type II, perinatal lethal form; OI type III, severe and progressively deforming, with normal sclera; and OI type IV, moderate severity with normal sclera. Approximately 90% of individuals with OI are heterozygous for mutations in the COL1A1 and COL1A2 genes, with dominant pattern of inheritance or sporadic mutations. After 2006, mutations were identified in the CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, and TMEM38B genes, associated with recessive OI and mutation in the IFITM5 gene associated with dominant OI. Mutations in PLS3 were recently identified in families with osteoporosis and fractures, with X-linked inheritance pattern. In addition to the genetic complexity of the molecular basis of OI, extensive phenotypic variability resulting from individual loci has also been documented. CONCLUSIONS: Considering the discovery of new genes and limited genotype-phenotype correlation, the use of next-generation sequencing tools has become useful in molecular studies of OI cases. The recommendation of the Nosology Group of the International Society of Skeletal Dysplasias is to maintain the classification of Sillence as the prototypical form, universally accepted to classify the degree of severity in OI, while maintaining it free from direct molecular reference.

  15. Animal models of osteogenesis imperfecta: applications in clinical research

    Directory of Open Access Journals (Sweden)

    Enderli TA

    2016-09-01

    Full Text Available Tanya A Enderli, Stephanie R Burtch, Jara N Templet, Alessandra Carriero Department of Biomedical Engineering, Florida Institute of Technology, Melbourne, FL, USA Abstract: Osteogenesis imperfecta (OI, commonly known as brittle bone disease, is a genetic disease characterized by extreme bone fragility and consequent skeletal deformities. This connective tissue disorder is caused by mutations in the quality and quantity of the collagen that in turn affect the overall mechanical integrity of the bone, increasing its vulnerability to fracture. Animal models of the disease have played a critical role in the understanding of the pathology and causes of OI and in the investigation of a broad range of clinical therapies for the disease. Currently, at least 20 animal models have been officially recognized to represent the phenotype and biochemistry of the 17 different types of OI in humans. These include mice, dogs, and fish. Here, we describe each of the animal models and the type of OI they represent, and present their application in clinical research for treatments of OI, such as drug therapies (ie, bisphosphonates and sclerostin and mechanical (ie, vibrational loading. In the future, different dosages and lengths of treatment need to be further investigated on different animal models of OI using potentially promising treatments, such as cellular and chaperone therapies. A combination of therapies may also offer a viable treatment regime to improve bone quality and reduce fragility in animals before being introduced into clinical trials for OI patients. Keywords: OI, brittle bone, clinical research, mouse, dog, zebrafish

  16. [Zoledronic acid (zoledronate) in children with osteogenesis imperfecta].

    Science.gov (United States)

    Sánchez-Sánchez, Luz María; Cabrera-Pedroza, Alfredo Uriel; Palacios-Saucedo, Gerardo; de la Fuente-Cortez, Beatriz

    2015-01-01

    Zoledronic acid or zo/edronate is a potent bisphosphonate that recently has been used in children with osteoporosis and osteogenesis imperfecta (01), so it could be an option in the treatment of children with this terrible disease that virtually condemns them to a life of pain and prostration. The aim of this study was to evaluate the clinical and biochemical conditions of pediatric patients with 01 before and after treatment with zo /edronate. We included 14 patients, median age six years (6 months to 14 years), eight (57.1 %) males and six (42 .9%) females, weight 19 kg (5.8-45 kg). According to the type of 01, six (42.9%) were type I, six (42.9%) type Ill, and two (14.2%) type IV The functional score (Bleck) previous to treatment was 4 (1-9) and 6 (2-9) after treatment (p = 0.001). Pain intensity prior to zo/edronate was 2 (1-9) and 0 (0-2) after (p = 0.008). Previous fractures five (1-15) and post-treatment one (0-2) (p = 0.001 ). There were no significant differences in calcium, phosphorus, alkaline phosphatase, and parathyroid hormone. Zoledronic acid decreases the number of bone fractures and pain in children with osteogenesis imperfect and improves functional status. The most common side effects were fever and bone pain within five days after the infusion,which disappear paracetamol. No adverse long-term effects such as hypocalcemia or hypoparathyroidism were reported.

  17. Serum creatine kinase isoenzymes in children with osteogenesis imperfecta.

    Science.gov (United States)

    D'Eufemia, P; Finocchiaro, R; Zambrano, A; Lodato, V; Celli, L; Finocchiaro, S; Persiani, P; Turchetti, A; Celli, M

    2017-01-01

    This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs.

  18. Mortality and morbidity in patients with osteogenesis imperfecta in Denmark.

    Science.gov (United States)

    Folkestad, Lars

    2018-04-01

    Ostegenesis imperfecta (OI) is a hereditary disease of the connective tissue caused by mutations to, mainly, the genes that are involved in the biosynthesis of collagen type 1. Patients are grouped according to clinical severity and mode of inheritance according to Sillence's classification (originally 1979, updated 2014). According to our data, the population prevalence of OI in Denmark was 10.3 per 100,000, with 575 patients registered with an OI diagnosis in the National Patient Register and alive at the end of 2012 out of a total population of 5,602,628 persons. Hallmarks of the disease are multiple fractures, blue sclera and varying degrees of bone deformities. Collagen type 1 is the most abundant collagen in the body and is an important part of the structure and function of the heart and lungs, the skeleton and many other organs. We hypothesize that patients with OI will have increased prevalence and risk of fractures throughout life, lower bone mineral density (BMD), impaired bone microstructure and bone geometry and increased risk of cardiovascular diseasesthus increased risk of all cause mortality compared to the general population. 
This thesis is a systematic search and narrative review covering the four main areas of interest of the PhD scholarship (risk and causes of death, fracture rates, bone mineral density, -geometry and -microstructure and cardiovascular diseases in OI). In addition to the review the thesis include the following four studies:
 1) Study 1 aimed to investigate the main causes of death and the risk of premature death in patients with OI in Denmark. We used a nationwide, registry-based, cohort study design, and included all patients registered in the National Patient Register with an OI diagnosis and a matched reference population randomly selected from the Danish Civil Service Register (matched 5:1, on gender and month and year of birth for each OI patient). We identified 687 patients with OI (25,615 person years at risk) and a

  19. Ruptured intracranial aneurysm in patients with osteogenesis imperfecta: 2 familial cases and a systematic review of the literature.

    Science.gov (United States)

    Gaberel, T; Rochey, A; di Palma, C; Lucas, F; Touze, E; Emery, E

    2016-12-01

    Osteogenesis imperfecta is an inherited connective tissue disorder that causes bone fragility. Vascular complications have been described, but only few cases of ruptured intracranial aneurysm have been reported. We first described 2 familial cases of ruptured intracranial aneurysm and then conducted a systematic review of the literature. A mother and her daughter with a typical history of osteogenesis imperfecta presented with subarachnoid hemorrhage, which was related to a posterior communicating artery aneurysm in both cases. The mother had early rebleeding and died. The aneurysm was excluded by coiling in the daughter. Despite occurrence of hydrocephalus and delayed cerebral ischemia, she had an excellent functional outcome. A systematic review of the literature identified seven additional cases. None of the cases were in fact familial. All patients had a previous medical history of multiple fractures. Seven aneurysms were resolved, three by surgical clipping and four by endovascular procedure. No periprocedural complication was reported. One patient died prematurely and 6 experienced good functional outcome. We report the first familial cases of aneurysmal subarachnoid hemorrhage in osteogenesis imperfecta patients. Intracranial aneurysms are probably linked to a collagen pathology, which is at the origin of osteogenesis imperfecta. In cases of aneurysmal subarachnoid hemorrhage in an osteogenesis imperfecta family, intracranial aneurysm screenings in the relatives showing osteogenesis imperfecta should be considered. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Osteogenesis imperfecta in childhood: MR imaging of basilar impression

    Energy Technology Data Exchange (ETDEWEB)

    Janus, G.J.M. E-mail: janus@knmg.nl; Engelbert, R.H.H.; Beek, E.; Gooskens, R.H.J.M.; Pruijs, J.E.H

    2003-07-01

    Objective: To determine on radiographs the presence of Basilar Impression (BI) in children with Osteogenesis Imperfecta (OI). To confirm this sign and altered geometrical relationships of the craniocervical junction in course of time with magnetic resonance imaging (MRI). Methods and patients: In a cohort study of 130 patients with OI (OI type I: 85; OI type III: 21; OI type IV: 24) lateral radiographs of the skull and cervical spine were made in a standardised way. MRI scans were performed when BI was suspected based upon protrusion of the odontoid above Chamberlain's line. Intracranial abnormalities as well as the basal angle were described. Neurological examination was performed in patients with conclusive BI at MRI-scan. Results and discussion: In eight patients BI could be confirmed by MRI-scan. None of the children had or developed in time neurological symptoms or signs. Follow up of BI by MRI scans was done in seven patients (mean: 5 years; range: 2-6 years). No alteration of intracranial findings were seen at subsequent investigation, although in one child Chamberlain's line increased from 8 (first MRI) to 15 mm (last MRI). BI can be diagnosed by radiographs but in the extreme osteoporotic bone and altered anatomy of the craniocervical junction of children with OI MRI is preferable. As intracranial pathology can be demonstrated by MRI, also a relation can be laid to possible neurological symptoms and signs at clinical examination. Conclusion: In our cohort study no alteration of the intracranial contents was seen at subsequent MRI scans. Although anatomic deformations exist in BI, no neurological symptoms or signs were present in our study and no operative reconstruction had to be performed. Periodical MRI-scan has not been of influence on the clinical decision making process. At the moment we perform a MRI-scan if BI is suspected at lateral skull radiographs. The MRI images serve as reference findings to anticipate on possible future symptoms and

  1. Exome Sequencing Identifies Truncating Mutations in Human SERPINF1 in Autosomal-Recessive Osteogenesis Imperfecta

    OpenAIRE

    Becker, Jutta; Semler, Oliver; Gilissen, Christian; Li, Yun; Bolz, Hanno Jörn; Giunta, Cecilia; Bergmann, Carsten; Rohrbach, Marianne; Koerber, Friederike; Zimmermann, Katharina; de Vries, Petra; Wirth, Brunhilde; Schoenau, Eckhard; Wollnik, Bernd; Veltman, Joris A.

    2011-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous genetic disorder characterized by bone fragility and susceptibility to fractures after minimal trauma. After mutations in all known OI genes had been excluded by Sanger sequencing, we applied next-generation sequencing to analyze the exome of a single individual who has a severe form of the disease and whose parents are second cousins. A total of 26,922 variations from the human reference genome sequence were subjected to several filtering steps...

  2. Sandwich allografts for long-bone nonunions in patients with osteogenesis imperfecta: a retrospective study.

    Science.gov (United States)

    Puvanesarajah, Varun; Shapiro, Jay R; Sponseller, Paul D

    2015-02-18

    Patients with osteogenesis imperfecta often develop nonunions, as internal fixation has limited applicability in this condition. We report the outcomes of a modified "sandwich technique" in the treatment of long-bone nonunions in patients with osteogenesis imperfecta; this technique brings circumferential stabilization and normal collagen to the nonunion site. From May 2003 through February 2012, twelve patients (eight females, four males; median age, 39.0 years; range, eleven to seventy-eight years) who had osteogenesis imperfecta (Sillence type I [three], type III [eight], and type IV [one]) and a combined total of thirteen nonunions (two humeral, two radial, three femoral, four tibial, and two ulnar; median duration, 15.0 months; range, six to 204 months) were treated at our institution with compressed sandwich allograft cortical struts. The struts were fashioned to be wide enough to allow for increased osteoconductive surface area and to approximate a hemicylindrical shape. Treatment history and demographics data were acquired through retrospective chart review. Follow-up radiographs were analyzed by two attending orthopaedic surgeons to determine radiographic findings. The median follow-up time was 4.6 years (range, 2.1 to 10.3 years). All thirteen nonunions, including one requiring a second graft procedure, healed with abundant, smooth allograft incorporation, resulting in an initial healing rate of 92% because of a refracture in one patient. This patient's nonunion ultimately healed with additional allograft struts and a new intramedullary rod. One patient required removal of prominent screws. The final follow-up examinations revealed no pain or refracture at the original nonunion site. All patients regained their prefracture level of function. Sandwich allograft struts constitute a durable, safe method for the stabilization and healing of persistent long-bone nonunions in patients with osteogenesis imperfecta. All patients showed incorporation of the

  3. Radiological manifestations of biphosphonate treatment with APD in a child suffering from osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Devogelaer, J.P.; Deuxchaisnes, C.N. de; Malghem, J.; Maldague, B.

    1987-07-01

    A 12-year-old female suffering fromosteogenesis imperfecta (OI) was treated with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD) orally, 250 mg daily, for periods of 2 months, alternating with periods of 2 months of abstinence. Total duration of therapy was 1 year. Radiological and clinical improvement was striking. Furthermore, X-rays of the bones showed large, parallel radio-opaque striae, corresponding exactly to the periods of therapy. These were present in all metaphyses.

  4. A rare presentation of a child with osteogenesis imperfecta and congenital laryngomalacia for herniotomy

    Directory of Open Access Journals (Sweden)

    Roshith Chandran

    2011-01-01

    Full Text Available Sometimes anaesthesiologists come across rare congenital anomalies in their practice. The inherent complications associated with the disorder necessitate tailor-made approaches for providing anaesthesia to even seemingly simple surgical interventions. Here, we share our experience of anaesthesia management of an infant with congenital laryngomalacia and recently diagnosed osteogenesis imperfecta type 1 who had presented to us with an acute abdomen for a semi-emergency herniotomy.

  5. Osteogenesis Imperfecta Type I-IV, the Collagenous Disorder of Connective Tissue in Czech Population

    Czech Academy of Sciences Publication Activity Database

    Šormová, L.; Mazura, Ivan

    2011-01-01

    Roč. 7, č. 1 (2011), s. 59-64 ISSN 1801-5603 R&D Projects: GA MŠk(CZ) 1M06014 Institutional research plan: CEZ:AV0Z10300504 Keywords : osteogenesis imperfecta * collagen type I * COL1A1 * COL1A2 * MLBR * mutations Subject RIV: IN - Informatics, Computer Science http://www.ejbi.eu/images/2011-1/Sormova_en.pdf

  6. Orthopaedic complications of osteogenesis imperfecta; Les complications orthopediques de l'osteogenese imparfaite

    Energy Technology Data Exchange (ETDEWEB)

    Azrak, S.; Ksyar, R.; Ben Rais, N. [hOpital Ibn Sina, CHU de Rabat-Sale, Service de Medecine Nucleaire, Rabat-Sale (Morocco)

    2009-12-15

    Osteogenesis imperfecta is a genetic disease characterized by bone frailty. It is generally caused by an abnormal production of collagen, which is the main fibrous protein of the bone. Collagen is also present in the skin, tendons, the sclera of the eye and dentin. The most frequent manifestation of osteogenesis imperfecta is the occurrence of multiple fractures without major trauma. Severity and timing of the attack varies widely: some patients sustain a significant number of fractures during early childhood which may have a serious impact on growth, while others will have some fractures separated by a few years. In all cases, the bone strength improves in adulthood. The bone fractures cause pain and bone deformities sometimes result in a smaller size. Scoliosis is frequent and associated with painful vertebral collapses. We present a case of osteogenesis imperfecta in a 40-year-old adult and we describe the various orthopaedic complications of the disease, stressing the role of bone scintigraphy in the diagnosis and monitoring of these complications. (authors)

  7. Osteogenesis imperfecta: Level of independence and of social, recreational and sports participation among adolescents and youth.

    Science.gov (United States)

    Rodríguez Celin, Mercedes; Fano, Virginia

    2016-06-01

    Osteogenesis imperfecta is a group of hereditary connective tissue disorders that cause bone fragility, with a wide clinical variability resulting in varying degrees of motor disability. To describe the level of independence and of social, recreational and sports participation among adolescents with osteogenesis imperfecta. Descriptive, analytical and crosssectional study conducted in patients with osteogenesis imperfecta older than 15 years old attending the Skeletal Dysplasia Office of Hospital "Prof. Dr. Juan P. Garrahan" (May 2013 through December 2014). Self-administered survey. Short stature was an outcome measure that indicated severity. There were 18 patients; age: 19.17 (±3.4 sDE); 83% had moderate-severe forms of OI; median height: -7.9 sDE; 50% used a wheelchair. Average education years: 12.2; 56% participated in sporting activities; and 78% were involved in recreational and social activities. A high level of independence was observed. We found a correlation between short stature and use of wheelchair (r: -0.77) and between short stature and participation in sporting activities (r: 0.66). No correlation was observed with years of education (r: -0.15), participation in social activities (r: -0.22) or recreational activities (r: 0.35). Sociedad Argentina de Pediatría.

  8. Two novel mutations in the PPIB gene cause a rare pedigree of osteogenesis imperfecta type IX.

    Science.gov (United States)

    Jiang, Yu; Pan, Jingxin; Guo, Dongwei; Zhang, Wei; Xie, Jie; Fang, Zishui; Guo, Chunmiao; Fang, Qun; Jiang, Weiying; Guo, Yibin

    2017-06-01

    Osteogenesis imperfecta (OI) is a rare genetic skeletal disorder characterized by increased bone fragility and vulnerability to fractures. PPIB is identified as a candidate gene for OI-IX, here we detect two pathogenic mutations in PPIB and analyze the genotype-phenotype correlation in a Chinese family with OI. Next-generation sequencing (NGS) was used to screen the whole exome of the parents of proband. Screening of variation frequency, evolutionary conservation comparisons, pathogenicity evaluation, and protein structure prediction were conducted to assess the pathogenicity of the novel mutations. Sanger sequencing was used to confirm the candidate variants. RTQ-PCR was used to analyze the PPIB gene expression. All mutant genes screened out by NGS were excluded except PPIB. Two novel heterozygous PPIB mutations (father, c.25A>G; mother, c.509G>A) were identified in relation to osteogenesis imperfecta type IX. Both mutations were predicted to be pathogenic by bioinformatics analysis and RTQ-PCR analysis revealed downregulated PPIB expression in the two carriers. We report a rare pedigree with an autosomal recessive osteogenesis imperfecta type IX (OI-IX) caused by two novel PPIB mutations identified for the first time in China. The current study expands our knowledge of PPIB mutations and their associated phenotypes, and provides new information on the genetic defects associated with this disease for clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A cephalometric method to diagnosis the craniovertebral junction abnormalities in osteogenesis imperfecta patients

    Science.gov (United States)

    Ríos-Rodenas, Mercedes; Gutiérrez-Díez, María-Pilar; Feijóo, Gonzalo; Mourelle, Maria-Rosa; Garcilazo, Mario; Ortega-Aranegui, Ricardo

    2015-01-01

    Osteogenesis imperfecta (OI) is a hereditary bone fragility disorder that in most patients is caused by mutations affecting collagen type I. Their typical oral and craneofacial characteristics (Dentinogenesis imperfecta type I and class III malocclusion), involve the dentist in the multidisciplinary team that treat these patients. It is usual to perform lateral skull radiographs for the orthodontic diagnosis. In addition, this radiograph is useful to analyse the junctional area between skull base and spine, that could be damaged in OI. Pathology in the craneovertebral junction (CVJ) is a serious complication of OI with a prevalence ranging from rare to 37%. To diagnosis early skull base anomalies in these patients, previously the neurological symptoms have been appear, we make a simple cephalometric analysis of the CVJ. This method has four measurements and one angle. Once we calculate the values of the OI patient, we compare the result with the mean and the standard deviations of an age-appropriate average in healthy controls. If the patient has a result more than 2,5 SDs above the age-appropriate average in healthy controls, we should to refer the patient to his/her pediatrician or neurologist. These doctors have to consider acquiring another diagnostic images to be used to determine cranial base measurements with more reliability. Thereby, dentists who treat these patients, must be aware of the normal radiological anatomy of the cervical spine on the lateral cephalogram. Key words:Osteogenesis imperfecta, craniovertebral junction, cephalometric. PMID:25810828

  10. ER stress-mediated apoptosis in a new mouse model of osteogenesis imperfecta.

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    Thomas S Lisse

    2008-02-01

    Full Text Available Osteogenesis imperfecta is an inherited disorder characterized by increased bone fragility, fractures, and osteoporosis, and most cases are caused by mutations affecting the type I collagen genes. Here, we describe a new mouse model for Osteogenesis imperfecta termed Aga2 (abnormal gait 2 that was isolated from the Munich N-ethyl-N-nitrosourea mutagenesis program and exhibited phenotypic variability, including reduced bone mass, multiple fractures, and early lethality. The causal gene was mapped to Chromosome 11 by linkage analysis, and a C-terminal frameshift mutation was identified in the Col1a1 (procollagen type I, alpha 1 gene as the cause of the disorder. Aga2 heterozygous animals had markedly increased bone turnover and a disrupted native collagen network. Further studies showed that abnormal proalpha1(I chains accumulated intracellularly in Aga2/+ dermal fibroblasts and were poorly secreted extracellularly. This was associated with the induction of an endoplasmic reticulum stress-specific unfolded protein response involving upregulation of BiP, Hsp47, and Gadd153 with caspases-12 and -3 activation and apoptosis of osteoblasts both in vitro and in vivo. These studies resulted in the identification of a new model for Osteogenesis imperfecta, and identified a role for intracellular modulation of the endoplasmic reticulum stress-associated unfolded protein response machinery toward osteoblast apoptosis during the pathogenesis of disease.

  11. Osteogenesis Imperfecta with Celiac Disease and Type II Diabetes Mellitus Associated: Improvement with a Gluten-Free Diet

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    Luis Rodrigo

    2012-01-01

    Full Text Available Osteogenesis imperfecta (OI is a genetic disease, with a connective tissue alteration, consisting in the presence of multiple spontaneous fractures or after minimal traumatism. Its association with other metabolic processes is rarely described. We present the clinical case of a female adult patient of 43 years. From her infancy, she has had multiple fractures, needing several surgical interventions, and she was diagnosed of OI type 2 at adolescence age. Due mainly to difficulties in walking remaining in wheel-chair in the last three years, she was overweight with morbid obesity (BMI=45.4 and had a type-II DM associated. She suffered from recurrent abdominal pain and chronic diarrhea and was diagnosed of celiac disease (CD with increased intraepithelial duodenal infiltration, being classified as lymphocytic enteritis, Marsh I type. She was put on a gluten-free diet (GFD, having lost 6 kg of weight after 6 months, with a good control of DM-II and presenting a significant clinical improvement. It is rewarding to search the presence of two coincidental metabolic diseases associated to OI, specially CD, because of the dramatic clinical benefit in the general found after putting on a GFD.

  12. Osteogenesis Imperfecta with Celiac Disease and Type II Diabetes Mellitus Associated: Improvement with a Gluten-Free Diet

    Science.gov (United States)

    Rodrigo, Luis; Pérez-Martinez, Isabel

    2012-01-01

    Osteogenesis imperfecta (OI) is a genetic disease, with a connective tissue alteration, consisting in the presence of multiple spontaneous fractures or after minimal traumatism. Its association with other metabolic processes is rarely described. We present the clinical case of a female adult patient of 43 years. From her infancy, she has had multiple fractures, needing several surgical interventions, and she was diagnosed of OI type 2 at adolescence age. Due mainly to difficulties in walking remaining in wheel-chair in the last three years, she was overweight with morbid obesity (BMI = 45.4) and had a type-II DM associated. She suffered from recurrent abdominal pain and chronic diarrhea and was diagnosed of celiac disease (CD) with increased intraepithelial duodenal infiltration, being classified as lymphocytic enteritis, Marsh I type. She was put on a gluten-free diet (GFD), having lost 6 kg of weight after 6 months, with a good control of DM-II and presenting a significant clinical improvement. It is rewarding to search the presence of two coincidental metabolic diseases associated to OI, specially CD, because of the dramatic clinical benefit in the general found after putting on a GFD. PMID:22481956

  13. Phase angle and World Health Organization criteria for the assessment of nutritional status in children with osteogenesis imperfecta.

    Science.gov (United States)

    Pileggi, Vicky Nogueira; Scalize, Antonio Rodolpho Hakime; Camelo Junior, José Simon

    2016-12-01

    To compare the phase angle of patients with osteogenesis imperfecta treated at a tertiary university hospital with patients in a control group of healthy children, and to assess the nutritional status of these patients through the body mass index proposed by the World Health Organization. Cross-sectional study carried out in a university hospital that included seven patients with osteogenesis imperfecta and a control group of 17 healthy children of the same gender and age. Weight and height were measured and bioelectrical impedance was performed. Subsequently, the phase angle was calculated based on resistance and reactance values. The phase angle of the group of children with osteogenesis imperfecta was significantly lower than that of the control group (posteogenesis imperfecta have a nutritional risk detected by the phase angle, which is a useful tool for nutritional screening. The calculation result could help in the diet therapy of patients with osteogenesis imperfecta. Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  14. Systematic review on the incidence of bisphosphonate related osteonecrosis of the jaw in children diagnosed with osteogenesis imperfecta.

    Science.gov (United States)

    Hennedige, Anusha Adeline; Jayasinghe, Jap; Khajeh, Janette; Macfarlane, Tatiana V

    2013-10-01

    To conduct a systematic review of epidemiological literature to determine the incidence of bisphosphonate related osteonecrosis of the jaw occurring either spontaneously or after dental surgery, in children and adolescents diagnosed with osteogenesis imperfecta. MEDLINE, HMIC and EMBASE were used to search for English-language articles published from 1946 - 2013. Inclusion criteria consisted of population based studies of children and adolescents (24 years and younger) diagnosed with osteogenesis imperfecta, only studies which included a dental examination, and patients treated with intravenous bisphosphonates were included. Articles were excluded if patients had any other co-morbidity which could affect osteonecrosis of the jaw, and those which treated patients with oral bisphosphonates only. Five studies consisting of four retrospective cohort studies and one case series were identified. Study populations ranged from 15 to 278 patients and number of subjects with osteogenesis imperfecta ranged from 15 to 221. Mean duration of intravenous bisphosphonate use ranged from 4.5 to 6.8 years. All patients were clinically examined and no patients were found to have osteonecrosis of the jaw. There is no evidence to support hypothesis of causal relationship between bisphosphonates and osteonecrosis of the jaw in children and adolescents with osteogenesis imperfecta. More prospective studies on bisphosphonate use in osteogenesis imperfecta needs to be carried out.

  15. Burnei's technique of femoral neck variation and valgisation by using the intramedullary rod in Osteogenesis imperfecta.

    Science.gov (United States)

    Georgescu, I; Gavriliu, Șt; Nepaliuc, I; Munteanu, L; Țiripa, I; Ghiță, R; Japie, E; Hamei, S; Dughilă, C; Macadon, M

    2014-01-01

    Varus or valgus deviations of the femoral neck in osteogenesis imperfecta have been an ignored chapter because the classic correction procedures were applied in medical practice with unsatisfying results. Until the use of telescopic rods, coronal deviations remained unsolved and the distal configuration of the proximal femoral extremity remained uncorrected or partially corrected, which required an extensive use of the wheel chair or bed immobilization of the patient. The concomitant correction of the complex deformities, coxa vara/valga and femoral integrated configuration, have been a progress which allowed the patients to walk with or without support. The purpose of this study is to present the Burnei's technique, a therapeutic alternative in deformity corrections of the varus or valgus hip in children with osteogenesis imperfecta. The paper is about a retrospective study done in a single center, which analyses Burnei technique and other procedures described in literature. The content of the article is based on a 12 years experience on a batch of 51 patients with osteogenesis imperfecta from which 10 patients (13 hips) presented frontal plane deviations of the femoral neck. All the patients with osteogenesis imperfecta who presented coxa vara or valga were submitted to investigations with the purpose of measuring blood loss, the possibility of extending the surgical intervention to the leg, the association of severe deformities of the proximal extremity of the femur and the necessity of postoperative intensive care. Burnei's technique: The operation was first performed in 2002. A subtrochanteric osteotomy was made in an oblique cut, from the internal side to the external side and from proximal to distal for coxa vara, or by using a cuneiform resection associated with muscular disinsertions. Only telescopic rods were used for osteosynthesis. There are a few articles in literature, which approach corrections of vara or valgus deviations in osteogenesis imperfecta

  16. Statistical characteristics and correlations of histomorphometric, clinical and biochemical indices in systemic therapy in patients with osteogenesis imperfecta

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    V. V. Hryhorovskyi

    2015-04-01

    Full Text Available Actuality. The correlation analysis between various indices of bone tissue condition was not previously carried out in patients with osteogenesis imperfecta. Aim. On purpose to determine differences and index correlations before and after intake of pamidronate systemic therapy in 13 patients with osteogenesis imperfecta indices of some methods including histomorphometric were studied. Results. We found correlation parametres of biochemical indices, on one side and histomorphometric – on the other. Conclusion. After systemic therapy mean parametres of «bone volume» in iliobiopsies increase, and «osteoid surface» and «osteoclast index per surface unit» in patients with osteogenesis imperfecta of I type – decrease, that one can regard as a tendency to improvement of the bone tissue structural-functional condition.

  17. Gene expression profiling of bone marrow mesenchymal stem cells from Osteogenesis Imperfecta patients during osteoblast differentiation.

    Science.gov (United States)

    Kaneto, Carla Martins; Pereira Lima, Patrícia S; Prata, Karen Lima; Dos Santos, Jane Lima; de Pina Neto, João Monteiro; Panepucci, Rodrigo Alexandre; Noushmehr, Houtan; Covas, Dimas Tadeu; de Paula, Francisco José Alburquerque; Silva, Wilson Araújo

    2017-06-01

    Mesenchymal stem cells (MSCs) are precursors present in adult bone marrow that are able to differentiate into osteoblasts, adipocytes and chondroblasts that have gained great importance as a source for cell therapy. Recently, a number of studies involving the analysis of gene expression of undifferentiated MSCs and of MSCs in the differentiation into multiple lineage processes were observed but there is no information concerning the gene expression of MSCs from Osteogenesis Imperfecta (OI) patients. Osteogenesis Imperfecta is characterized as a genetic disorder in which a generalized osteopenia leads to excessive bone fragility and severe bone deformities. The aim of this study was to analyze gene expression profile during osteogenic differentiation from BMMSCs (Bone Marrow Mesenchymal Stem Cells) obtained from patients with Osteogenesis Imperfecta and from control subjects. Bone marrow samples were collected from three normal subjects and five patients with OI. Mononuclear cells were isolated for obtaining mesenchymal cells that had been expanded until osteogenic differentiation was induced. RNA was harvested at seven time points during the osteogenic differentiation period (D0, D+1, D+2, D+7, D+12, D+17 and D+21). Gene expression analysis was performed by the microarray technique and identified several differentially expressed genes. Some important genes for osteoblast differentiation had lower expression in OI patients, suggesting a smaller commitment of these patient's MSCs with the osteogenic lineage. Other genes also had their differential expression confirmed by RT-qPCR. An increase in the expression of genes related to adipocytes was observed, suggesting an increase of adipogenic differentiation at the expense osteogenic differentiation. Copyright © 2017. Published by Elsevier Masson SAS.

  18. Multiple Spontaneous Intracranial-Extracranial Arterial Dissections in a Patient with Osteogenesis Imperfecta

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    Mehmet Kolukısa

    2017-01-01

    Full Text Available A 40-year-old male with osteogenesis imperfecta (OI was admitted to the hospital with an acute right monoparesis. Diffusion-weighted MRI showed infarction in the territory of the left anterior cerebral artery (ACA and in the left posterior cerebral artery (PCA. In his vascular imaging, occlusion of the left vertebral artery (VA starting from V2 segment was consistent with dissection and pseudoaneurysm in the right ACA. We presented this case because of the presence of spontaneous and simultaneous occurrence of both intracranial and extracranial arterial dissections in OI.

  19. Corneal cross-linking in a child with osteogenesis imperfecta syndrome and keratoconus

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    Sergio Kwitko

    2017-07-01

    Full Text Available Cross-linking (CXL is a well-established procedure in children with keratoconus (KC, but cases of CXL and osteogenesis imperfecta (OI have not been published in the literature, despite the association between physiopathology of these diseases. This is the first case, to the best of our knowledge, of a young girl with both OI and KC that underwent a CXL treatment. In this case, CXL was performed at 6-years-old prior to an expected progression, without complications and probably stopped further keratoconus progression.

  20. Effect of osteogenesis imperfecta mutations in tropocollagen molecule on strength of biomimetic tropocollagen-hydroxyapatite nanocomposites

    Science.gov (United States)

    Dubey, Devendra K.; Tomar, Vikas

    2010-01-01

    Osteogenesis Imperfecta (OI) is a genetic disorder that affects cellular synthesis of Type-I collagen fibrils and causes extreme bone fragility. This study reports the effects of OI mutations in Tropocollagen (TC) molecules on strength of model Tropocollagen-Hydroxyapatite biomaterials with two different mineral [hydroxyapatite (HAP)] distributions using three dimensional atomistic simulations. Results show that the effect of TC mutations on the strength of TC-HAP biomaterials is insignificant. Instead, change in mineral distribution showed significant impact on the overall strength of TC-HAP biomaterials. Study suggests that TC mutations manifest themselves by changing the mineral distribution during hydroxyapatite growth and nucleation period.

  1. La unión craneocervical en el paciente con osteogénesis imperfecta

    OpenAIRE

    Ríos Ródenas, Mercedes

    2016-01-01

    La Osteogénesis Imperfecta (OI) es una enfermedad genética que se caracteriza por una reducción de la masa ósea con fragilidad ósea asociada. Los pacientes tienen tendencia a la fractura, por lo que también se la conoce como enfermedad de “huesos de cristal”. Por su baja incidencia, de 1:15.000 a 1:20.000 recién nacidos, está catalogada dentro del grupo de enfermedades raras. Estos pacientes, suelen presentar anomalías dentales y problemas oclusales severos que determinan que el odontólogo de...

  2. Perinatal lethal osteogenesis imperfecta in a Thai newborn: the autopsy and histopathogical findings.

    Science.gov (United States)

    Himakhun, Wanwisa; Rojnueangnit, Kitiwan; Prachukthum, Sariya

    2012-01-01

    Osteogenesis imperfecta (OI) is an inherited disorder of type I collagen synthesis with an estimate incidence of I in 100,000 live births. Among all types, OI type II is the most severe type with perinatal death. The authors describes a male neonate with characteristic features of osteogenesis imperfect type II, including short crumpling limbs, beaded ribs, poorly bony ossification and blue sclera. Autopsy with histological study revealed not only multiple fractures, but pulmonary hypoplasia and intracerebral hemorrhages were also present. Both are the leading causes of death in the lethal type OI patients.

  3. Novel FKBP10 Mutation in a Patient with Osteogenesis Imperfecta Type XI.

    Science.gov (United States)

    Seyedhassani, Seyed Mohammad; Hashemi-Gorji, Feyzollah; Yavari, Mahdieh; Harazi, Fahimeh; Yassaee, Vahid Reza

    2016-01-01

    Osteogenesis imperfecta (OI) is a set of clinically and genetically heterogeneous disorders with autosomal dominant, recessive and X-linked inheritance patterns. The aim of this study was to describe a novel genetic abnormality in a case of OI type XI with mild joint contractures, kyphoscoliosis, muscular atrophy, progressively deforming and multiple bone fractures in a consanguineous Iranian family. Based on the phenotype, investigation of two candidate genes, CRTAP (OI type VII) and FKBP10 (OI type XI) detected a novel homozygous frameshift mutation in the FKBP10 gene. This finding can be useful in accurate genetic counseling and prioritization of molecular analysis of OI in Iranian patients.

  4. Abordaje interdisciplinario de tres hermanas con Amelogénesis imperfecta: Reporte de Caso

    OpenAIRE

    Brenes A., Alejandra; Montero S., Olman

    2011-01-01

    Tres hermanas con edades de 7, 9 y 12 años fueron atendidas en la clínica del Posgrado de Odontopediatría de la Universidad de Costa Rica; ellas presentaban amelogénesis imperfecta tipo hipoplásico y mordida abierta anterior. La higiene bucodental en las tres, era muy deficiente, lo que obligó el abordaje con sesiones de fase higiénica que permitieran posteriormente, iniciar el tratamiento rehabilitador. Cada caso fue estudiado en forma independiente. Se hizo necesario proceder interdisciplin...

  5. Investigation of the Human Disease Osteogenesis Imperfecta: A Research-Based Introduction to Concepts and Skills in Biomolecular Analysis

    Science.gov (United States)

    Mate, Karen; Sim, Alistair; Weidenhofer, Judith; Milward, Liz; Scott, Judith

    2013-01-01

    A blended approach encompassing problem-based learning (PBL) and structured inquiry was used in this laboratory exercise based on the congenital disease Osteogenesis imperfecta (OI), to introduce commonly used techniques in biomolecular analysis within a clinical context. During a series of PBL sessions students were presented with several…

  6. Hyperplastic callus formation in osteogenesis imperfecta type V mimicking osteosarcoma: 4-year follow-up with resolution

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    Vieira, R.L.V.; Amaral, D.T. [Federal University of Sao Paulo, Department of Radiology, Sao Paulo (Brazil); Jesus-Garcia, Filho R. [Federal University of Sao Paulo, Department of Orthopedic Surgery, Sao Paulo (Brazil); Saraiva, G. [Federal University of Sao Paulo, Department of Endocrinology, Sao Paulo (Brazil); Fernandes, A.R.C. [University of California San Diego, Department of MSK Radiology, San Diego, CA (United States); Resnick, D.

    2006-06-15

    We report a case of hyperplastic callus formation that occurred in both femurs in a patient with type V osteogenesis imperfecta (OI), with 4-year follow-up and resolution. The clinical, histological and imaging aspects of this condition are discussed. Recognition of the hyperplastic callus formation in this particular type of OI is important in order to avoid misdiagnosis. (orig.)

  7. Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with osteogenesis imperfecta.

    Science.gov (United States)

    Albert, Carolyne; Jameson, John; Smith, Peter; Harris, Gerald

    2014-09-01

    Osteogenesis imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64-68% lower in the transverse vs. longitudinal beams (Posteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight toward understanding bone fragility and the role of intracortical porosity on the strength of bone tissue in children with osteogenesis imperfecta. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study

    NARCIS (Netherlands)

    Sakkers, Ralph; Kok, Dieke; Engelbert, Raoul; van Dongen, Alice; Jansen, Maarten; Pruijs, Hans; Verbout, Ab; Schweitzer, Dave; Uiterwaal, Cuno

    2004-01-01

    Non-randomised studies have suggested beneficial effects of bisphosphonates in osteogenesis imperfecta. We assessed the effects of oral olpadronate in children with this disorder in a randomised double-blind placebo-controlled trial. 34 children recruited from the Dutch national centre for

  9. CRTAP mutations in lethal and severe osteogenesis imperfecta: the importance of combining biochemical and molecular genetic analysis.

    NARCIS (Netherlands)

    Dijk, F.S. Van; Nesbitt, I.M.; Nikkels, P.G.J.; Dalton, A.; Bongers, E.M.H.F.; Kamp, J.M. van de; Hilhorst-Hofstee, Y.; Hollander, N.S. den; Lachmeijer, A.M.; Marcelis, C.L.M.; Tan-Sindhunata, G.M.; Rijn, R.R. van; Meijers-Heijboer, H.; Cobben, J.M.; Pals, G.

    2009-01-01

    Autosomal recessive lethal and severe osteogenesis imperfecta (OI) is caused by the deficiency of cartilage-associated protein (CRTAP) and prolyl-3-hydroxylase 1 (P3H1) because of CRTAP and LEPRE1 mutations. We analyzed five families in which 10 individuals had a clinical diagnosis of lethal and

  10. 10-m shuttle ride test in youth with osteogenesis imperfecta who use wheelchairs : Feasibility, reproducibility, and physiological responses

    NARCIS (Netherlands)

    Bongers, Bart C.; Rijks, Ester B G; Harsevoort, Arjan G J; Takken, Tim|info:eu-repo/dai/nl/184586674; van Brussel, Marco|info:eu-repo/dai/nl/30481962X

    2016-01-01

    Background: Physical fitness levels in youth with osteogenesis imperfecta (OI) who use wheelchairs are unknown. The 10-m Shuttle Ride Test (SRiT) has recently been introduced as a field test to determine cardiorespiratory fitness in children with cerebral palsy who selfpropel a wheelchair.

  11. Results of a bone splint technique for the treatment of lower limb deformities in children with type I osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Dasheng Lin

    2013-01-01

    Full Text Available Background: Children with osteogenesis imperfecta (OI can suffer from frequent fractures and limb deformities, resulting in impaired ambulation. Osteopenia and thin cortices complicate orthopedic treatment in this group. This study evaluates the clinical results of a bone splint technique for the treatment of lower limb deformities in children with type I OI. The technique consists of internal plating combined with cortical strut allograft fixation. Materials and Methods: We prospectively followed nine children (five boys, four girls with lower limb deformities due to type I OI, who had been treated with the bone splint technique (11 femurs, four tibias between 2003 and 2006. The fracture healing time, deformity improvement, ambulation ability and complications were recorded to evaluate treatment effects. Results: At the time of surgery the average age in our study was 7.7 years (range 5-12 years. The average length of followup was 69 months (range 60-84 months. All patients had good fracture healing with an average healing time of 14 weeks (range 12-16 weeks and none experienced further fractures, deformity, or nonunion. The fixation remained stable throughout the procedure in all cases, with no evidence of loosening or breakage of screws and the deformity and mobility significantly improved after surgery. Of the two children confined to bed before surgery, one was able to walk on crutches and the other needed a wheelchair. The other seven patients could walk without walking aids or support like crutches. Conclusions: These findings suggest that the bone splint technique provides good mechanical support and increases the bone mass. It is an effective treatment for children with OI and lower limb deformities.

  12. A novel mutation in LEPRE1 that eliminates only the KDEL ER- retrieval sequence causes non-lethal osteogenesis imperfecta.

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    Masaki Takagi

    Full Text Available Prolyl 3-hydroxylase 1 (P3H1, encoded by the LEPRE1 gene, forms a molecular complex with cartilage-associated protein (CRTAP and cyclophilin B (encoded by PPIB in the endoplasmic reticulum (ER. This complex is responsible for one step in collagen post-translational modification, the prolyl 3-hydroxylation of specific proline residues, specifically α1(I Pro986. P3H1 provides the enzymatic activity of the complex and has a Lys-Asp-Glu-Leu (KDEL ER-retrieval sequence at the carboxyl terminus. Loss of function mutations in LEPRE1 lead to the Pro986 residue remaining unmodified and lead to slow folding and excessive helical post-translational modification of type I collagen, which is seen in both dominant and recessive osteogenesis imperfecta (OI. Here, we present the case of siblings with non-lethal OI due to novel compound heterozygous mutations in LEPRE1 (c.484delG and c.2155dupC. The results of RNA analysis and real-time PCR suggest that mRNA with c.2155dupC escapes from nonsense-mediated RNA decay. Without the KDEL ER- retrieval sequence, the product of the c.2155dupC variant cannot be retained in the ER. This is the first report of a mutation in LEPRE1 that eliminates only the KDEL ER-retrieval sequence, whereas other functional domains remain intact. Our study shows, for the first time, that the KDEL ER- retrieval sequence is essential for P3H1 functionality and that a defect in KDEL is sufficient for disease onset.

  13. The chaperone activity of 4PBA ameliorates the skeletal phenotype of Chihuahua, a zebrafish model for dominant osteogenesis imperfecta.

    Science.gov (United States)

    Gioia, Roberta; Tonelli, Francesca; Ceppi, Ilaria; Biggiogera, Marco; Leikin, Sergey; Fisher, Shannon; Tenedini, Elena; Yorgan, Timur A; Schinke, Thorsten; Tian, Kun; Schwartz, Jean-Marc; Forte, Fabiana; Wagener, Raimund; Villani, Simona; Rossi, Antonio; Forlino, Antonella

    2017-08-01

    Classical osteogenesis imperfecta (OI) is a bone disease caused by type I collagen mutations and characterized by bone fragility, frequent fractures in absence of trauma and growth deficiency. No definitive cure is available for OI and to develop novel drug therapies, taking advantage of a repositioning strategy, the small teleost zebrafish (Danio rerio) is a particularly appealing model. Its small size, high proliferative rate, embryo transparency and small amount of drug required make zebrafish the model of choice for drug screening studies, when a valid disease model is available. We performed a deep characterization of the zebrafish mutant Chihuahua, that carries a G574D (p.G736D) substitution in the α1 chain of type I collagen. We successfully validated it as a model for classical OI. Growth of mutants was delayed compared with WT. X-ray, µCT, alizarin red/alcian blue and calcein staining revealed severe skeletal deformity, presence of fractures and delayed mineralization. Type I collagen extracted from different tissues showed abnormal electrophoretic migration and low melting temperature. The presence of endoplasmic reticulum (ER) enlargement due to mutant collagen retention in osteoblasts and fibroblasts of mutant fish was shown by electron and confocal microscopy. Two chemical chaperones, 4PBA and TUDCA, were used to ameliorate the cellular stress and indeed 4PBA ameliorated bone mineralization in larvae and skeletal deformities in adult, mainly acting on reducing ER cisternae size and favoring collagen secretion. In conclusion, our data demonstrated that ER stress is a novel target to ameliorate OI phenotype; chemical chaperones such as 4PBA may be, alone or in combination, a new class of molecules to be further investigated for OI treatment. © The Author 2017. Published by Oxford University Press.

  14. Correlation of Bone Mineral Density on Quality of Life in Patients with Osteogenesis Imperfecta during Treatment with Denosumab.

    Science.gov (United States)

    Hoyer-Kuhn, Heike; Stark, Christina; Franklin, Jeremy; Schoenau, Eckhard; Semler, Oliver

    2017-11-01

    Osteogenesis imperfecta (OI) is a rare hereditary skeletal disease leading to recurrent fractures, short stature and impaired mobility. The phenotype varies from mildly affected patients to perinatal lethal forms. In most cases an impaired collagen production due to mutations in COL1A1 or COL1A2 cause this hereditary bone fragility syndrome with an autosomal dominant inheritance. Currently an interdisciplinary therapeutic approach with antiresorptive drugs, physiotherapy and surgical procedures is the state of the art therapy. The effect of such a therapy is evaluated by measuring different surrogate parameters like areal bone mineral density or by using different mobility tests or questionnaires. Up till now the impact of these parameters on quality of life of the patients is not evaluated. Currently pharmacological strategies are based on antiresorptive treatment with bisphosphonates. In this trial we investigated the effect of an antiresorptive therapy with the monoclonal antibody denosumab decreasing the activity of osteoclasts. Denosumab was administered subcutaneously in a dose of 1mg/kg body weight in 10 children with OI (5-10 years of age) every 12 weeks for 48 weeks. Areal bone mineral density, mobility, pain scores and quality of life were measured. The results showed a good effect of the treatment on bone mineral density but this improvement showed no correlation to pain and quality of life. In conclusion further trials have to define parameters to assess interventions which influence activities of daily life of the patients. An interdisciplinary approach including physicians, basic researchers and patient organisation is needed to focus research on topics improving quality of life of patients with severe skeletal diseases. Copyright© of YS Medical Media ltd.

  15. Tooth agenesis in osteogenesis imperfecta related to mutations in the collagen type I genes.

    Science.gov (United States)

    Malmgren, B; Andersson, K; Lindahl, K; Kindmark, A; Grigelioniene, G; Zachariadis, V; Dahllöf, G; Åström, E

    2017-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, mainly caused by mutations in the collagen type I genes (COL1A1 and COL1A2). Tooth agenesis is a common feature of OI. We investigated the association between tooth agenesis and collagen type I mutations in individuals with OI. In this cohort study, 128 unrelated individuals with OI were included. Panoramic radiographs were analyzed regarding dentinogenesis imperfecta (DGI) and congenitally missing teeth. The collagen I genes were sequenced in all individuals, and in 25, multiplex ligation-dependent probe amplification was performed. Mutations in the COL1A1 and COL1A2 genes were found in 104 of 128 individuals. Tooth agenesis was diagnosed in 17% (hypodontia 11%, oligodontia 6%) and was more frequent in those with DGI (P = 0.016), and in those with OI type III, 47%, compared to those with OI types I, 12% (P = 0.003), and IV, 13% (P = 0.017). Seventy-five percent of the individuals with oligodontia (≥6 missing teeth) had qualitative mutations, but there was no association with OI type, gender, or presence of DGI. The prevalence of tooth agenesis is high (17%) in individuals with OI, and OI caused by a qualitative collagen I mutation is associated with oligodontia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Compuestos elásticos no lineales con condiciones de contacto imperfectas

    Directory of Open Access Journals (Sweden)

    Juan C. López Realpozo

    2008-01-01

    Full Text Available En el siguiente trabajo, se obtiene la ley efectiva de un compuesto laminado elástico no lineal formado por dos constituyentes, para lo cual utilizamos el Método de Homogeneización Asintótica. Se trabaja con un compuesto bifásico formado de los materiales aluminio y acero, en el que se consideran condición de contacto perfecta e imperfecta (tipo spring y tipo membrana entre las constituyentes. En los tipos de contacto imperfecto considerados, se tienen ambas constituyentes con propiedades isotrópicas. En este trabajo, se hace una extensión de resultados anteriormente publicados, donde solo se consideró condiciones de contacto perfecto entre las constituyentes para compuestos elásticos o piezoeléctricos. En este caso también se presentan algunos ejemplos numéricos donde se muestra que para los compuestos considerados, el Método de Homogeneización Asintótica es eficiente para determinar propiedades efectivas de compuestos en los cuales se considera condiciones de contacto imperfecta en la interfase.

  17. Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

    Science.gov (United States)

    Lindahl, Katarina; Åström, Eva; Rubin, Carl-Johan; Grigelioniene, Giedre; Malmgren, Barbro; Ljunggren, Östen; Kindmark, Andreas

    2015-01-01

    Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype–phenotype studies on >100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1- and α2-chains were associated with the absence of dentinogenesis imperfecta (P95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in >95% of an entire OI population. PMID:25944380

  18. Combined Treatment with Laser Sintering and Zirconium: A Case Report of Dentinogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Simel Ayyildiz

    2013-01-01

    Full Text Available Osteogenesis imperfecta (OI is a heterogeneous disorder of connective tissue that manifests mainly as skeletal deformity and bone fragility. Dentinogenesis imperfecta (DI is sometimes an accompanying symptom of OI. The treatment protocol of these patients varies according to the clinical appearance. The case report here describes complete mouth rehabilitation of an 18-year-old male patient with OI and DI using direct metal laser sintering (DMLS technique of metal-ceramic restorations and zirconium all-ceramic crowns. DMLS is an additive metal fabrication technology that is simpler, more precise, and healthier than conventional manufacturing and can be remarkably cost effective. Moreover, the technique affords highly accurate production of fixed partial dentures with ideal marginal fit and excellent mechanical properties. The patient was treated using a multidisciplinary strategy that focused on controlling caries, protecting teeth from further wear, obtaining an appropriate vertical dimension, and providing soft tissue support to return the facial profile to a normal appearance using new technology in the field of prosthetics.

  19. Homozygosity for a Missense Mutation in SERPINH1, which Encodes the Collagen Chaperone Protein HSP47, Results in Severe Recessive Osteogenesis Imperfecta

    OpenAIRE

    Christiansen, Helena E.; Schwarze, Ulrike; Pyott, Shawna M.; AlSwaid, Abdulrahman; Al Balwi, Mohammed; Alrasheed, Shatha; Pepin, Melanie G.; Weis, Mary Ann; Eyre, David R.; Byers, Peter H.

    2010-01-01

    Osteogenesis imperfecta (OI) is characterized by bone fragility and fractures that may be accompanied by bone deformity, dentinogenesis imperfecta, short stature, and shortened life span. About 90% of individuals with OI have dominant mutations in the type I collagen genes COL1A1 and COL1A2. Recessive forms of OI resulting from mutations in collagen-modifying enzymes and chaperones CRTAP, LEPRE1, PPIB, and FKBP10 have recently been identified. We have identified an autosomal-recessive missens...

  20. An N-terminal glycine to cysteine mutation in the collagen COL1A1 gene produces moderately severe osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Wilcox, W.; Scott, L.; Cohn, D. [Cedars-Sinai Medical Center, Los Angeles, CA (United States)

    1994-09-01

    Osteogenesis imperfecta (OI) is usually due to mutations in the type I procollagen genes COL1A1 and COL1A2. Point mutations close to the N-terminus are generally milder than those near the C-terminus of the molecule (the gradient hypothesis of collagen mutations). We describe a patient with moderately severe OI due to a mutation in the N-terminal portion of the triple helical domain of the {alpha}1(I) chain. Electrophoretic analysis of collagen isolated from fibroblast cultures suggested the abnormal presence of a cysteine in the N-terminal portion of the {alpha}1(I) chain. Five overlapping DNA fragments amplified from fibroblast RNA were screened for mutations using single strand conformational polymorphism (SSCP) and heteroduplex analyses. Direct DNA sequence analysis of the single positive fragment demonstrated a G to T transversion, corresponding to a glycine to cysteine substitution at position 226 of the triple helical domain of the {alpha}1(I) chain. The mutation was confirmed by restriction enzyme analysis of amplified genomic DNA. The mutation was not present in fibroblasts from either phenotypically normal parent. Combining this mutation with other reported mutations, glycine to cysteine substitutions at positions 205, 211, 223, and 226 produce a moderately severe phenotype whereas flanking mutations at positions 175 and 382 produce a mild phenotype. This data supports a regional rather than a gradient model of the relationship between the nature and location of type I collagen mutations and OI phenotype.

  1. Standardized X-ray reports of the spine in osteogenesis imperfecta; Standard zur Befundung von Roentgenaufnahmen der Wirbelsaeule bei Patienten mit Osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Koerber, Friederike; Demant, A.W.; Koerber, S. [Universitaetsklinikum Koeln (Germany). Kinderradiologie, Inst. und Poliklinik fuer Radiologische Diagnostik; Semler, O.; Schoenau, E. [Universitaetsklinikum Koeln (Germany). Osteologie, Klinik und Poliklinik fuer Allgemeine Kinderheilkunde; Lackner, K.J. [Universitaetsklinikum Koeln (Germany). Inst. und Poliklinik fuer Radiologische Diagnostik

    2011-05-15

    Purpose: In this study we present a standard for radiological reports in patients with osteogenesis imperfecta (OI). The parameters can be used to describe X-rays of the lateral spine and give an impartial description of anatomical structures during a treatment with bisphosphonates. Material and Methods: In this retrospective analysis we included 48 patients with OI (31 female, 17 male [1.5 months - 19 years, mean age 9.0 years]). Lateral spine X-rays were analyzed by 2 radiologists before and during treatment. The parameters of the standardized report are degree of kyphoscoliosis, compression of single vertebrae, predominant type of vertebral deformities and extent of vertebral compression (score 1 - 5). Results: There was no clear trend in the change of compression of single vertebrae. Some vertebrae with ventral compression showed an upgrowth to vertebrae with harmonic compression. Other deformities showed only marginal changes. In 26 patients the kyphoscoliosis improved (mean 10 degrees), in 36 patients the thoracic vertebrae compression increased and in 30 patients the vertebral height in the lumbar spine increased. The improvement of vertebral height was 1 point in the thoracic and lumbar spine. Conclusion: We propose a standardized report of X-rays of the lateral spine in patients with OI with quantitative and semiquantitative parameters using morphological criteria. These include compression of single vertebrae, degree of kyphoscoliosis, vertebral deformities and the severity of vertebral compression in the thoracic and lumbar spine. (orig.)

  2. Orthopaedic and dental abnormalities in osteogenesis imperfecta: a review of the literature.

    Science.gov (United States)

    Scaramuzzo, L; Raffaelli, L; Spinelli, M S; Damis, G; Maccauro, G; Manicone, P F

    2011-01-01

    Osteogenesis imperfecta is one of the most commonly recognized inheritable disorders of the connective tissue leading to bone fragility. Usually it is associated to a genetic mutation inducing a reduction in collagen quality and entity production. It involves either modification in dentin formation or multiple bone fractures. The authors reviewed the clinical aspects of these disorders, focusing on oral and orthopaedic concerns, especially related to the histological features of the fracture callus, with respect to new trends in pharmacological and surgical treatments of bone fractures. Surgical treatment varies, according to the age of the patient. In children, surgical orthopaedic procedures include multiple osteotomies and the use of telescopic rods. Medical therapy has always to be associated to surgery and is designed to reduce the incidence of fractures, to increase growth velocity and to ally pain in order to improve mobility and independence. Bisphosphonates (BP) are considered potent inhibitors of bone resorption decreasing the osteoclast population and its activity and bone turn over.

  3. Osteogenesis imperfecta type III/Ehlers-Danlos overlap syndrome in a Chinese man.

    Science.gov (United States)

    Lu, Yanqin; Wang, Yanzhou; Rauch, Frank; Li, Hu; Zhang, Yao; Zhai, Naixiang; Zhang, Jian; Ren, Xiuzhi; Han, Jinxiang

    2018-02-01

    Osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) are rare genetic disorders that are typically inherited in an autosomal dominant manner. Few cases of OI/EDS overlap syndrome have been documented. Described here is a 30-year-old Chinese male with OI type III and EDS. Sequencing of genomic DNA revealed a heterozygous COL1A1 mutation (c.671G>A, p.Gly224Asp) that affected the N-anchor domain of the alpha 1 chain of collagen type I. Ultrastructural analysis of a skin biopsy specimen revealed thin collagen fibers with irregular alignment of collagen fibers. These findings have expanded the genotypic spectrum of the OI/EDS overlap syndrome.

  4. Bone tissue ultrastructural defects in a mouse model for osteogenesis imperfecta: a Raman spectroscopy study

    Science.gov (United States)

    Chen, Tsoching; Kozloff, Kenneth M.; Goldstein, Steven A.; Morris, Michael D.

    2004-07-01

    Osteogenesis imperfecta (OI) is genetic defect in which the genes that code for the α1(I) or α2(I) chains of type I collagen are defective. The defects often result in substitution of a bulky amino acid for glycine, causing formation of collagen that can not form the normal triple helix. Depending on the details of the defects, the outcomes range from controllable to lethal. This study focuses on OI type IV, a more common and moderately severe form of the disease. People with the disease have a substantial increase in the risk and rate of fracture. We examine the spectroscopic consequences of these defects, using a mouse model (BRTL) that mimics OI type IV. We compare Raman images from tibial cortical tissue of wild-type mice and BRTL mice with single copy of mutation and show that both mineral to matrix ratios and collagen inter-fibril cross-links are different in wild-type and mutant mice.

  5. MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

    Science.gov (United States)

    Lindert, Uschi; Cabral, Wayne A.; Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Ludin, Katja; Barnes, Aileen M.; Yeetong, Patra; Weis, Maryann; Krabichler, Birgit; Srichomthong, Chalurmpon; Makareeva, Elena N.; Janecke, Andreas R.; Leikin, Sergey; Röthlisberger, Benno; Rohrbach, Marianne; Kennerknecht, Ingo; Eyre, David R.; Suphapeetiporn, Kanya; Giunta, Cecilia; Marini, Joan C.; Shotelersuk, Vorasuk

    2016-01-01

    Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development. PMID:27380894

  6. Rare co-occurrence of osteogenesis imperfecta type I and autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Hoefele, Julia; Mayer, Karin; Marschall, Christoph; Alberer, Martin; Klein, Hanns-Georg; Kirschstein, Martin

    2016-11-01

    There are several clinical reports about the co-occurrence of autosomal dominant polycystic kidney disease (ADPKD) and connective tissue disorders. A simultaneous occurrence of osteogenesis imperfecta (OI) type I and ADPKD has not been observed so far. This report presents the first patient with OI type I and ADPKD. Mutational analysis of PKD1 and COL1A1 in the index patient revealed a heterozygous mutation in each of the two genes. Mutational analysis of the parents indicated the mother as a carrier of the PKD1 mutation and the father as a carrier of the COL1A1 mutation. The simultaneous occurrence of both disorders has an estimated frequency of 3.5:100 000 000. In singular cases, ADPKD can occur in combination with other rare disorders, e.g. connective tissue disorders.

  7. Health-Related Quality of Life in Adults with Osteogenesis Imperfecta

    DEFF Research Database (Denmark)

    Hald, Jannie Dahl; Folkestad, Lars; Harsløf, Torben

    2017-01-01

    Osteogenesis imperfecta (OI) is a systemic connective tissue disorder most often caused by mutations in collagen type 1 related genes. Patients with OI suffer from multiple fractures and various degrees of growth deficiency and bone deformity. It is unknown whether the systemic effect of defect...... skeletal- and non-skeletal phenotypes and patient demographics. We investigated physical and mental HRQoL using a validated questionnaire, SF-36, and compared the data to values obtained in a population without OI. Patients with mild, moderate, and severe OI all had lower mean scores on domains describing...... physical HRQoL and a lower mean physical component score compared to the general population, p mental HRQoL were more inhomogenously affected, but did not differ significantly from...

  8. Total femur arthroplasty for revision hip failure in osteogenesis imperfecta: limits of biology

    Directory of Open Access Journals (Sweden)

    Pablo Sanz-Ruiz, PhD, MD

    2017-09-01

    Full Text Available Osteogenesis imperfecta (OI is a rare congenital disease characterized by alterations in bone quality, with susceptibility to fractures, instability, deformities, and osteoarthrosis. Prosthetic surgery in these patients is associated with an abnormally high rate of implant failures. On the other hand, abnormal bone fragility adds to the complexity of revision surgery in such individuals—thus representing a genuine challenge for the orthopaedic surgeon. We present a case of femoral reconstruction in a patient with OI and prosthetic loosening after reconstruction secondary to femoral septic pseudoarthrosis. Intramedullary total femoral reconstruction was carried out after exceeding the biological reconstruction limits. This is the first reported instance of the use of an intramedullary total femur arthroplasty as salvage technique in an OI patient. This technique should be considered when we have exceeded biological limits for femoral fixation.

  9. Intravitreal bevacizumab for treatment of choroidal neovascularization associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2012-01-01

    Full Text Available A 12-year-old girl, diagnosed of osteogenesis imperfecta, presented with sudden visual loss in the left eye. Investigations revealed an active choroidal neovascular membrane. She underwent treatment with intravitreal Bevacizumab (1.25 mg/0.05 ml. Follow-up at 1 month revealed the development of lacquer crack running through the macula, underlying the fovea. The patient received two re-treatments at 1-month intervals, following which the choroidal neovascularization (CNV regressed completely. However, further progression of lacquer cracks was noted. At the last follow-up, 6 months following the last injection, the fundus remained stable and vision was maintained at 20/200. Considering the natural history of the disease and the increased risk of rupture of the Bruch′s membrane in such eyes, the possible complication of a lacquer crack developing must be borne in mind, before initiating treatment.

  10. Effects of bisphosphonates on tooth eruption in children with osteogenesis imperfecta.

    Science.gov (United States)

    Kamoun-Goldrat, Agnès; Ginisty, Danielle; Le Merrer, Martine

    2008-06-01

    Bisphosphonates are currently used in the therapy of osteogenesis imperfecta (OI) to decrease the bone fragility observed in OI patients. Bisphosphonate therapy delays tooth eruption in rats. The aim of this study was to determine whether or not bisphosphonate therapy delays tooth eruption in children. The clinical emergence of teeth was observed and the calculated dental age and the number of delayed teeth were determined for 33 OI patients treated with bisphosphonates and for strictly gender- and age-matched controls. There were significant differences between bisphosphonate-treated patients and controls for calculated dental age and number of delayed teeth. Bisphosphonate therapy was associated with a mean delay of 1.67 yr in tooth eruption in children with OI.

  11. [Children with osteogenesis imperfecta. An infrequent but important disease].

    Science.gov (United States)

    Fernández Maldonado, A I; Gutiérrez Alonso, J L

    2001-05-01

    Imperfect osteogenesis is a disease which is included in the group of the osseous dysplasias having a heterogeneous genetic character and whose basic defect is an alteration in the synthesis of Procollagen I. This leads to a serious fragility in skeletal structures as well as in exoskeletal structures, causing multiple fractures and deformities. The absence of a truly effective medical, surgical or orthopedic treatment makes correctly planned nursing care acquire vital importance in order to succeed in avoiding, and diminishing, fractures and deformities due to an inadequate handling of these patients; while to the contrary contributing to success in integrating these patients into society in the best possible conditions. This is the first of two articles which the authors will dedicate to this disease; this disease will be described in this first article, while the second one will concentrate exclusively on nursing treatments recommended for patients suffering from this disease.

  12. Comparison of Calcitonin and Pamidronate Treatments in Children with Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Neslihan Onenli Mungan

    2013-08-01

    Full Text Available Purpose: The main objective of this study was to compare the treatments of calcitonin and pamidronate by clinical, biochemical, and radiological findings in children with osteogenesis imperfecta and evaluate the efficiency of pamidronate treatment. Patients and methods: A total of 12 patients, aged 41±38 (1-120 months were studied. Group 1 was consisted of six patients who had received intranasal calcitonin at a dosage of 4-6 U/kg three times a week before switching to pamidronate treatment. Group 2 was also consisted of six patients who had received only pamidronate infusion at a dosage of 0.5-2 mg/kg every two months. Results: Annual fracture rates decreased from 2.72 ± 0.80 to 0.40 ± 0.70 (p0.05, and from -3.08 ± -0.61 to -2.29 ± -0.56 in pamidronate group. The difference between the Z-scores of bone mineral density after calcitonin and pamidronate treatments was statistically significant (p<0.05. The Z-scores of pre (-3.44 ± -0.96 and post (-2.47 ± -0.60 pamidronate treatments of whole 12 patients were significantly different (p<0.001. Conclusion: Pamidronate was significantly more effective in reducing pain, annual fracture rate, and increasing bone mineral density and mobility than calcitonin without any severe adverse effects even in the neonatal period and severe forms of osteogenesis imperfecta. [Cukurova Med J 2013; 38(4.000: 667-674

  13. What every clinical geneticist should know about testing for osteogenesis imperfecta in suspected child abuse cases.

    Science.gov (United States)

    Pepin, Melanie G; Byers, Peter H

    2015-12-01

    Non-accidental injury (NAI) is a major medical concern in the United States. One of the challenges in evaluation of children with unexplained fractures is that genetic forms of bone fragility are one of the differential diagnoses. Infants who present with fractures with mild forms of osteogenesis imperfecta (OI) (OI type I or OI type IV), the most common genetic form of bone disease leading to fractures might be missed if clinical evaluation alone is used to make the diagnosis. Diagnostic clinical features (blue sclera, dentinogenesis imperfecta, Wormian bones on X-rays or positive family history) may not be present or apparent at the age of evaluation. The evaluating clinician faces the decision about whether genetic testing is necessary in certain NAI cases. In this review, we outline clinical presentations of mild OI and review the history of genetic testing for OI in the NAI versus OI setting. We summarize our data of molecular testing in the Collagen Diagnostic Laboratory (CDL) from 2008 to 2014 where NAI was noted on the request for DNA sequencing of COL1A1 and COL1A2. We provide recommendations for molecular testing in the NAI versus OI setting. First, DNA sequencing of COL1A1, COL1A2, and IFITM5 simultaneously and duplication/deletion testing is recommended. If a causative variant is not identified, in the absence of a pathologic clinical phenotype, no additional gene testing is indicated. If a VUS is found, parental segregation studies are recommended. © 2015 Wiley Periodicals, Inc.

  14. In vivo laser confocal microscopy findings of a cornea with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Kobayashi A

    2014-02-01

    Full Text Available Akira Kobayashi, Tomomi Higashide, Hideaki Yokogawa, Natsuko Yamazaki, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Objective: To report the in vivo laser confocal microscopy findings of a cornea with osteogenesis imperfecta (OI with special attention to the abnormality of Bowman's layer and sub-Bowman's fibrous structures (K-structures. Patients and methods: Two patients (67-year-old male and his 26-year-old son with OI type I were included in this study. Slit lamp biomicroscopic and in vivo laser confocal microscopic examinations were performed for both patients. Central corneal thickness and central endothelial cell density were also measured. Results: Although the corneas looked clear with normal endothelial density for both eyes in both patients, they were quite thin (386 µm oculus dexter (OD (the right eye and 384 µm oculus sinister (OS (the left eye in the father and 430 µm OD and 425 µm OS in the son. In both patients, slit lamp biomicroscopic and in vivo laser confocal microscopic examination showed similar results. Anterior corneal mosaics produced by rubbing the eyelid under fluorescein were completely absent in both eyes. In vivo laser confocal microscopy revealed an absent or atrophic Bowman's layer; a trace of a presumed Bowman's layer and/or basement membrane was barely visible with high intensity. Additionally, K-structures were completely absent in both eyes. Conclusion: The absence of K-structures and fluorescein anterior corneal mosaics strongly suggested an abnormality of Bowman's layer in these OI patients. Keywords: osteogenesis imperfecta, K-structure, confocal microscopy, Bowman's layer

  15. La paz imperfecta en el marco del conflicto político armado en Colombia

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    Héctor Alonso Moreno-Parra

    2014-01-01

    Full Text Available A fin de comprender la dimensión del conflicto estructural que ha generado tanta violencia en nuestro país, determinar y precisar los momentos y episodios de obstrucción política del bipartidismo como modelo hegemónico de gobierno; y determinar los momentos de construcción de un nuevo concepto de paz como paz imperfecta, es necesario explicar las dinámicas políticas, sociales, y de producción, que han permitido históricamente que se exprese una relación dicotómica: violencia-bipartidismo. Relación que ha sido un factor determinante en el desarrollo político de la vida del país y uno de los factores constitutivos de conflictos sociales violentos y de exclusión política. De manera especial, esta relación violencia-bipartidismo se ha constituido en un gran obstáculo para el avance de las llamadas terceras fuerzas políticas autónomas; y además, ha contribuido a la marginalidad y la liquidación de las mismas. En este sentido, el aporte de este artículo es establecer que a partir del concepto de paz imperfecta y de la relación violencia bipartidismo, también es posible desde otra perspectiva ontológica y epistemológica establecer un nuevo concepto de paz que permita desde allí, plantear una nueva caracterización de tercerías políticas a partir de los pactos políticos, y de manera particular del pacto del Frente Nacional de 1958, y del Pacto Constituyente de 1990.

  16. The potential research impact of patient reported outcomes on osteogenesis imperfecta.

    Science.gov (United States)

    Brownstein, Catherine A; Wicks, Paul

    2010-10-01

    Osteogenesis imperfecta (OI) is an inherited connective tissue disorder with many phenotypic presentations ranging from mild to severe. It is often called "brittle bone disease." Treatment consists of physical therapy, surgical interventions, medications and, in some cases, experimental therapies. Because treatment is not standardized and is often experimental, information on the success of different methods is usually not available or well documented. We therefore asked if social networking can make OI patients' lives better. How would a bone disorder community work? Is it possible for patients to know how well they are doing in comparison to others like them, and if they are getting the most successful treatment for their disease? An evaluation of how PatientsLikeMe®, a personal research and social networking website and database for patients with life changing illnesses, can aid in improving patient outcomes through the anonymous sharing of medical information. PatientsLikeMe® could help patients answer the question, "Given my condition, what is the best outcome I could hope to achieve, and how do I get there?" Participants could record their real-time day-to-day progress in achieving their treatment goals, such as preventing fractures, and share that with the community to help patients, caregivers, researchers and industry learn more about OI. Social networking can change the lives of Osteogenesis Imperfecta patients for the better, and make them a part of the treatment discovery process. Here we present a possible OI online community and demonstrate its potential utility for patients and medical professionals alike.

  17. Increased nuchal translucency and short femur length as possible early signs of osteogenesis imperfecta type III.

    Science.gov (United States)

    Vimercati, Antonella; Panzarino, Mariantonietta; Totaro, Ilaria; Chincoli, Annarosa; Selvaggi, Luigi

    2013-01-01

    this paper reports an association between an increased Nuchal Translucency (NT) and Osteogenesis Imperfecta (OI), a type of skeletal dysplasia. Measurement of fetal NT at 10-14 weeks of gestation is a sensitive and effective screening method for chromosomal abnormalities. a 35-year- old Caucasian woman in her fourth pregnancy was referred to our clinic for an ultrasound scan at 12 weeks of gestation, that confirmed increased Nuchal Translucency. Chorionic villi sampling was performed, showing a normal karyotype. The patient was evaluated by a team of experienced ultra sonographers for pregnancy follow-up at our Department, that is a tertiary center. in our case the ultrasound scan at 12 week of gestation revealed only an increased NT (3 mm). Cytogenetic analysis on chorionic villi demonstrated a normal male karyotype. US follow-up, performed every 3-4 weeks, confirmed normal anthropometric parameters except for shortening of both femurs, but at 23 weeks an incorrect attitude of the feet was revealed. A clinical and radiographic diagnosis of OI type III was made only at birth, and through follow-up continuing to date. NT screening was successful for chromosomal abnormalities at 11-14 weeks of gestation. An increased NT thickness is also associated with numerous fetal anomalies and genetic syndromes in a chromosomally normal fetus. In our case there were no sonographic signs of imperfect osteogenesis in the first trimester, although there was an increased NT with a normal karyotype. currently, in literature, there are not other cases of OI type III associated with an increased NT. Our report is the first to suggest an association between an increased nuchal translucency, short femur length and osteogenesis imperfecta type III.

  18. EFFECTS OF LONG-TERM ALENDRONATE TREATMENT ON A LARGE SAMPLE OF PEDIATRIC PATIENTS WITH OSTEOGENESIS IMPERFECTA.

    Science.gov (United States)

    Lv, Fang; Liu, Yi; Xu, Xiaojie; Wang, Jianyi; Ma, Doudou; Jiang, Yan; Wang, Ou; Xia, Weibo; Xing, Xiaoping; Yu, Wei; Li, Mei

    2016-12-01

    Osteogenesis imperfecta (OI) is a group of inherited diseases characterized by reduced bone mass, recurrent bone fractures, and progressive bone deformities. Here, we evaluate the efficacy and safety of long-term treatment with alendronate in a large sample of Chinese children and adolescents with OI. In this prospective study, a total of 91 children and adolescents with OI were included. The patients received 3 years' treatment with 70 mg alendronate weekly and 500 mg calcium daily. During the treatment, fracture incidence, bone mineral density (BMD), and serum levels of the bone turnover biomarkers (alkaline phosphatase [ALP] and cross-linked C-telopeptide of type I collagen [β-CTX]) were evaluated. Linear growth speed and parameters of safety were also measured. After 3 years of treatment, the mean annual fracture incidence decreased from 1.2 ± 0.8 to 0.2 ± 0.3 (Posteogenesis imperfecta PTH = parathyroid hormone.

  19. Four patients with Sillence type I osteogenesis imperfecta and mild bone fragility, complicated by left ventricular cardiac valvular disease and cardiac tissue fragility caused by type I collagen mutations

    DEFF Research Database (Denmark)

    Vandersteen, Anthony M; Lund, Allan M; Ferguson, David J P

    2014-01-01

    Osteogenesis imperfecta (OI) type I is a hereditary disorder of connective tissue (HDCT) characterized by blue or gray sclerae, variable short stature, dentinogenesis imperfecta, hearing loss, and recurrent fractures from infancy. We present four examples of OI type I complicated by valvular heart...

  20. Mutation analysis of the COL1A1 and COL1A2 genes in Vietnamese patients with osteogenesis imperfecta

    OpenAIRE

    Ho Duy, Binh; Zhytnik, Lidiia; Maasalu, Katre; Kändla, Ivo; Prans, Ele; Reimann, Ene; Märtson, Aare; Kõks, Sulev

    2016-01-01

    Background: The genetics of osteogenesis imperfecta (OI) have not been studied in a Vietnamese population before. We performed mutational analysis of the COL1A1 and COL1A2 genes in 91 unrelated OI patients of Vietnamese origin. We then systematically characterized the mutation profiles of these two genes which are most commonly related to OI.Methods: Genomic DNA was extracted from EDTA-preserved blood according to standard high-salt extraction methods. Sequence analysis and pathogenic variant...

  1. Vliv typu mutace v genu COL1A1 na fenotyp osob s diagnózou osteogenesis imperfecta

    Czech Academy of Sciences Publication Activity Database

    Šormová, L.; Mazurová, F.; Mazura, Ivan

    2008-01-01

    Roč. 15, 3-4 (2008), s. 332-338 ISSN 1212-4575. [Diagnostic, Comprehensive Treatment and Biomechanics of Locomotor Effects. Prague-Sydney-Lublin Symposium /10./. Prague, 24.09.2008-25.09.2008] R&D Projects: GA MŠk(CZ) 1M06014 Institutional research plan: CEZ:AV0Z10300504 Keywords : osteogenesis imperfecta * COL1A1 * kolagen * kolagenopatie * mutace Subject RIV: EB - Genetics ; Molecular Biology

  2. Vliv typu mutace v genu COL1A2 na klinický obraz pacientů s osteogenesis imperfecta

    Czech Academy of Sciences Publication Activity Database

    Sluková, V.; Mazurová, F.; Mazura, Ivan

    2008-01-01

    Roč. 15, 3-4 (2008), s. 338-338 ISSN 1212-4575. [Diagnostic, Comprehensive Treatment and Biomechanics of Locomotor Effects. Prague-Sydney-Lublin Symposium /10./. 24.09.2008-25.09.2008, Prague] Institutional research plan: CEZ:AV0Z10300504 Keywords : osteogenesis imperfecta * kolagen * COL1A2 * regionální model Subject RIV: EB - Genetics ; Molecular Biology

  3. Eleven years of experience with bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I

    Directory of Open Access Journals (Sweden)

    Iwamoto J

    2012-12-01

    Full Text Available Jun Iwamoto,1 Yoshihiro Sato,2 Mitsuyoshi Uzawa,3 Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, 2Department of Neurology, Mitate Hospital, Fukuoka, 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanAbstract: We report the 11-year follow-up of a man with osteogenesis imperfecta type I who was treated with bisphosphonates and alfacalcidol. A 36-year-old Japanese man with osteogenesis imperfecta type I who had frequently experienced painful fragility fractures consulted our clinic because of chronic back pain. The patient had multiple morphometric vertebral fractures and a low bone mineral density (BMD at the lumbar spine. The patient was treated with cyclical etidronate 200 mg, for 2 weeks every 3 months, plus alfacalcidol 1 µg daily, for 2 years; and alendronate 5 mg daily or 35 mg weekly, plus alfacalcidol 1 µg daily for 9 years. After 11 years of treatment, BMD at the lumbar spine increased by 6.4%, following a 20.3% reduction in serum alkaline phosphatase. Serum calcium, phosphorus, and intact parathyroid hormone levels remained within the normal ranges. Three clinical fractures occurred at two ribs and the metacarpus, and two morphometric vertebral fractures occurred at the thoracic spine during the 11-year treatment period, but the patient experienced no adverse effects. Thus, the present case report shows the long-term outcome and safety of bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I.Keywords: etidronate, alendronate, fragility fracture, bone mineral density, osteogenesis imperfecta

  4. Corrective osteotomy with retrograde Fassier-Duval nail in an osteogenesis imperfecta patient with bilateral genu valgum

    OpenAIRE

    Lin, Tsung-Yu; Yang, Chen-Yu; Liu, Shih-Chia

    2017-01-01

    Abstract Rationale: The treatment of osteogenesis imperfecta (OI) requires a multidisciplinary approach to maximize function and reduce fracture incidence. The aim of this case report was to discuss an alternative surgical approach to stabilize a corrective osteotomy using the Fassier Duval (FD) system in an OI patient. Patient concerns: A 20-year-old OI woman presented with left thigh pain, gait disturbance, and bilateral genu valgus deformities. Diagnoses: Physical examination and standing ...

  5. SUCCESSFUL USE OF THE PONSETI METHOD IN THE TREATMENT OF FOUR CHILDREN WITH CLUBFOOT ASSOCIATED WITH OSTEOGENESIS IMPERFECTA TYPE I

    OpenAIRE

    Валерий Федорович Бландинский; Максим Александрович Вавилов; Максим Александрович Баушев

    2014-01-01

    Conservative treatment of congenital clubfoot deformity in osteogenesis imperfecta is very challenging because the high risk of pathological fracture. There is little to no data of such cases hadn’t been found to be described in the literature. We present a child with osteogenesis imperfect and clubfoot deformity, who had been previously inefficiently treated with plaster casts and developed pathological fractures of the tibia. The use of Ponseti method allowed us to completely correct the de...

  6. SUCCESSFUL USE OF THE PONSETI METHOD IN THE TREATMENT OF FOUR CHILDREN WITH CLUBFOOT ASSOCIATED WITH OSTEOGENESIS IMPERFECTA TYPE I

    Directory of Open Access Journals (Sweden)

    Валерий Федорович Бландинский

    2014-06-01

    Full Text Available Conservative treatment of congenital clubfoot deformity in osteogenesis imperfecta is very challenging because the high risk of pathological fracture. There is little to no data of such cases hadn’t been found to be described in the literature. We present a child with osteogenesis imperfect and clubfoot deformity, who had been previously inefficiently treated with plaster casts and developed pathological fractures of the tibia. The use of Ponseti method allowed us to completely correct the deformity and avoid complications.

  7. [Osteogenesis imperfecta: Treatment and results of a case series].

    Science.gov (United States)

    Escribano-Rey, R J; Duart-Clemente, J; Martínez de la Llana, O; Beguiristáin-Gúrpide, J L

    2014-01-01

    To describe our experience in the management of patients with osteogenesis imperfect (OI). We conducted a retrospective study of a series of cases affected with OI treated in the Clínica Univesidad de Navarra from 1980 to 2007, with a mean follow up of 17.3 years (7-27 years). We collected descriptive data of the sample, the fractures and the deformities, and the treatments given. The complications presented and the functional outcomes at the end of follow-up were also reviewed. The sample included ten patients. Approximately two-thirds (65%) of fractures were sustained in the lower limbs. One patient received medical treatment only. Three patients had combined medical and surgical treatment. Some type of surgical treatment was performed on 6 patients. The most common surgery was the Sofield-Millar performed on 37 occasions, with a third of them requiring revision surgery due to migration of the nails. There were 17 episodes of re-fracture. Complications such as non-union, iatrogenic fractures, and infections, were also observed. The functional outcome, according to the Hoffer-Bullock scale, at the end of follow-up was grade I/II in 7 patients. Despite the need for multiple interventions and complications presented during follow up, the appropriate treatment of patients with OI can provide acceptable functional outcomes. Copyright © 2012 SECOT. Published by Elsevier Espana. All rights reserved.

  8. Severe osteogenesis imperfecta caused by double glycine substitutions near the amino-terminal triple helical region in COL1A2.

    Science.gov (United States)

    Takagi, Masaki; Shinohara, Hiroyuki; Narumi, Satoshi; Nishimura, Gen; Hasegawa, Yukihiro; Hasegawa, Tomonobu

    2015-07-01

    Most cases of osteogenesis imperfecta (OI) are caused by heterozygous mutations in COL1A1 or COL1A2, the genes encoding the two type I procollagen alpha chains, proα1 (I) and proα2 (I). We report on a unique case of severe OI, a long term survivor of lethal type II OI, rather than progressively deforming type III, due to double substitutions of glycine residues in COL1A2 (p.Gly208Glu and p.Gly235Asp), located on the same allele. To the best of our knowledge, this is the first example of a patient with double COL1A2 glycine substitution mutations on the same allele. We show for the first time that double COL1A2 glycine substitution mutations located near the amino-terminal triple helical region, which individually are likely to result in mild OI, cause severe OI in combination. © 2015 Wiley Periodicals, Inc.

  9. Resource Centres for Rare Oral Diseases – Why?

    DEFF Research Database (Denmark)

    Daugaard-Jensen, Jette; Gjørup, Hans

    2010-01-01

    .5-73) and the male/female ratio was equal (1.06) Results: A: Oligodontia (N=154 ) and Amelogenesis Imperfecta (N=146 ) were the most frequently diagnosed dental anomalies. B: Osteogenesis Imperfecta (N=88), Ectodermal Dysplasia (N=81), Ehlers Danlos Syndrome (61) and Marfan Syndrome (N=44) were the largest groups...

  10. Bisphosphonates for the prevention of fractures in osteogenesis imperfecta: meta-analysis of placebo-controlled trials.

    Science.gov (United States)

    Hald, Jannie D; Evangelou, Evangelos; Langdahl, Bente L; Ralston, Stuart H

    2015-05-01

    Bisphosphonates are widely used off-label in the treatment of patients with osteogenesis imperfecta (OI) with the intention of reducing the risk of fracture. Although there is strong evidence that bisphosphonates increase bone mineral density in osteogenesis imperfecta, the effects on fracture occurrence have been inconsistent. The aim of this study was to gain a better insight into the effects of bisphosphonate therapy on fracture risk in patients with osteogenesis imperfecta by conducting a meta-analysis of randomized controlled trials in which fractures were a reported endpoint. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials in which the effects of bisphosphonates on fracture risk in osteogenesis imperfecta were compared with placebo and conducted a meta-analysis of these studies using standard methods. Heterogeneity was assessed using the I2 statistic. Six eligible studies were identified involving 424 subjects with 751 patient-years of follow-up. The proportion of patients who experienced a fracture was not significantly reduced by bisphosphonate therapy (Relative Risk [RR] = 0.83 [95% confidence interval 0.69-1.01], p = 0.06) with no heterogeneity between studies (I2  = 0). The fracture rate was reduced by bisphosphonate treatment when all studies were considered (RR = 0.71 [0.52-0.96], p = 0.02), but with considerable heterogeneity (I2  = 36%) explained by one study where a small number of patients in the placebo group experienced a large number of fractures. When this study was excluded, the effects of bisphosphonates on fracture rate was not significant (RR = 0.79 [0.61-1.02], p = 0.07, I2  = 0%). We conclude that the effects of bisphosphonates on fracture prevention in osteogenesis imperfecta are inconclusive. Adequately powered trials with a fracture endpoint are needed to further investigate the risks and benefits of bisphosphonates in this condition. © 2014 American Society for

  11. Due diligence

    International Nuclear Information System (INIS)

    Sanghera, G.S.

    1999-01-01

    The Occupational Health and Safety (OHS) Act requires that every employer shall ensure the health and safety of workers in the workplace. Issues regarding the practices at workplaces and how they should reflect the standards of due diligence were discussed. Due diligence was described as being the need for employers to identify hazards in the workplace and to take active steps to prevent workers from potentially dangerous incidents. The paper discussed various aspects of due diligence including policy, training, procedures, measurement and enforcement. The consequences of contravening the OHS Act were also described

  12. Osteogenesis imperfecta

    Science.gov (United States)

    ... OI may include: Bowed legs and arms Kyphosis Scoliosis (S-curve spine) ... are called bisphosphonates. Low impact exercises, such as swimming, keep muscles strong and help maintain strong bones. ...

  13. Alternativa en el tratamiento de la dentinogénesis imperfecta

    Directory of Open Access Journals (Sweden)

    Mirta Elena Montero del Castillo

    Full Text Available La dentinogénesis imperfecta es una afección hereditaria autosómica dominante que se origina en la etapa de histodiferenciación durante la odontogénesis. Constituye una forma de displasia mesodérmica localizada, caracterizada por una alteración de las proteínas dentinarias. El propósito de esta presentación es mostrar una alternativa en el tratamiento de esta afección en niños, utilizando coronas de acero inoxidables y resinas adhesivas compuestas. Se describe la forma en que se trató una niña de 8 años de edad que acudió a consulta por presentar dolor al ingerir alimentos fríos y dulces, cambios en la coloración y forma de los dientes, así como, alteraciones psicológicas en cuanto a su apariencia personal. Se corroboró la ausencia de antecedentes de esta afección en su familia. Se realizó examen clínico y radiográfico, donde se observaron las alteraciones en cuanto a forma y coloración de los dientes y pérdida de tejido dentario sobre todo en los primeros molares permanentes, con disminución de la dimensión vertical. Radiográficamente se constató la presencia de los folículos de sucesores permanentes, así como, estructuras óseas normales. Se diagnosticó dentinogénesis imperfecta. Se procedió a la colocación de coronas de acero inoxidable en los primeros molares permanentes y en los segundos molares temporales, para restaurar la dimensión vertical y solucionar las molestias a la ingestión de alimentos. Posteriormente se restauraron los dientes anteriores con resinas adhesivas compuestas. Es de vital importancia el diagnóstico y tratamiento temprano de esta afección para evitar grandes destrucciones de tejido, se muestra que en niños se debe realizar el tratamiento instalando coronas de acero inoxidables y restaurando los dientes con resinas adhesivas compuestas hasta esperar a la adultez donde se puedan realizar otros tipos de restauraciones definitivas.

  14. Microstructural and Photoacoustic Infrared Spectroscopic Studies of Human Cortical Bone with Osteogenesis Imperfecta

    Science.gov (United States)

    Gu, Chunju; Katti, Dinesh R.; Katti, Kalpana S.

    2016-04-01

    The molecular basis of bone disease osteogenesis imperfecta (OI) and the mineralization of hydroxyapatite in OI bone have been of significant research interest. To further investigate the mechanism of OI disease and bone mineralization, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy, and x-ray diffraction (XRD) are used in the present study to describe the structural and compositional differences between OI and healthy bone. OI bone exhibits more porous, fibrous features, abnormal collagen fibrils, and abnormal mineral deposits. Likewise, photoacoustic-FTIR experiments indicate an aberrant collagen structure and an altered mineral structure in OI. In contrast, there is neither significant difference in the non-collagenous proteins (NCPs) composition observed nor apparent change in the crystal structure between OI and healthy bone minerals as shown in XRD and energy-dispersive x-ray spectroscopy (EDS) results. This observation indicates that the biomineralization process is more controlled by the bone cells and non-collagenous phosphorylated proteins. The present study also confirms that there is an orientational influence on the stoichiometry of the mineral in OI bone. Also, a larger volume of the hydrated layer in the transverse plane than the longitudinal plane of the mineral crystal structure is proposed. The appearance of a new C-S band in the FTIR spectra in OI bone suggests the substitution of glycine by cysteine in collagen molecules or/and an increased amount of cysteine-rich osteonectin that relates to mineral nucleation and mineral crystal formation.

  15. Salubrinal improves mechanical properties of the femur in osteogenesis imperfecta mice.

    Science.gov (United States)

    Takigawa, Shinya; Frondorf, Brian; Liu, Shengzhi; Liu, Yang; Li, Baiyan; Sudo, Akihiro; Wallace, Joseph M; Yokota, Hiroki; Hamamura, Kazunori

    2016-10-01

    Salubrinal is an agent that reduces the stress to the endoplasmic reticulum by inhibiting de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). We and others have previously shown that the elevated phosphorylation of eIF2α stimulates bone formation and attenuates bone resorption. In this study, we applied salubrinal to a mouse model of osteogenesis imperfecta (Oim), and examined whether it would improve Oim's mechanical property. We conducted in vitro experiments using RAW264.7 pre-osteoclasts and bone marrow derived cells (BMDCs), and performed in vivo administration of salubrinal to Oim (+/-) mice. The animal study included two control groups (wildtype and Oim placebo). The result revealed that salubrinal decreased expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1) and suppressed osteoclast maturation, and it stimulated mineralization of mesenchymal stem cells from BMDCs. Furthermore, daily injection of salubrinal at 2 mg/kg for 2 months made stiffness (N/mm) and elastic module (GPa) of the femur undistinguishable to those of the wildtype control. Collectively, this study supported salubrinal's beneficial role to Oim's femora. Unlike bisphosphonates, salubrinal stimulates bone formation. For juvenile OI patients who may favor strengthening bone without inactivating bone remodeling, salubrinal may present a novel therapeutic option. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  16. Normal Collagen and Bone Production by Gene-targeted Human Osteogenesis Imperfecta iPSCs

    Science.gov (United States)

    Deyle, David R; Khan, Iram F; Ren, Gaoying; Wang, Pei-Rong; Kho, Jordan; Schwarze, Ulrike; Russell, David W

    2012-01-01

    Osteogenesis imperfecta (OI) is caused by dominant mutations in the type I collagen genes. In principle, the skeletal abnormalities of OI could be treated by transplantation of patient-specific, bone-forming cells that no longer express the mutant gene. Here, we develop this approach by isolating mesenchymal cells from OI patients, inactivating their mutant collagen genes by adeno-associated virus (AAV)-mediated gene targeting, and deriving induced pluripotent stem cells (iPSCs) that were expanded and differentiated into mesenchymal stem cells (iMSCs). Gene-targeted iMSCs produced normal collagen and formed bone in vivo, but were less senescent and proliferated more than bone-derived MSCs. To generate iPSCs that would be more appropriate for clinical use, the reprogramming and selectable marker transgenes were removed by Cre recombinase. These results demonstrate that the combination of gene targeting and iPSC derivation can be used to produce potentially therapeutic cells from patients with genetic disease. PMID:22031238

  17. Micro-CT characterization of human trabecular bone in osteogenesis imperfecta

    Science.gov (United States)

    Jameson, John; Albert, Carolyne; Smith, Peter; Molthen, Robert; Harris, Gerald

    2011-03-01

    Osteogenesis imperfecta (OI) is a genetic syndrome affecting collagen synthesis and assembly. Its symptoms vary widely but commonly include bone fragility, reduced stature, and bone deformity. Because of the small size and paucity of human specimens, there is a lack of biomechanical data for OI bone. Most literature has focused on histomorphometric analyses, which rely on assumptions to extrapolate 3-D properties. In this study, a micro-computed tomography (μCT) system was used to directly measure structural and mineral properties in pediatric OI bone collected during routine surgical procedures. Surface renderings suggested a poorly organized, plate-like orientation. Patients with a history of bone-augmenting drugs exhibited increased bone volume fraction (BV/TV), trabecular number (Tb.N), and connectivity density (Eu.Conn.D). The latter two parameters appeared to be related to OI severity. Structural results were consistently higher than those reported in a previous histomorphometric study, but these differences can be attributed to factors such as specimen collection site, drug therapy, and assumptions associated with histomorphometry. Mineral testing revealed strong correlations with several structural parameters, highlighting the importance of a dual approach in trabecular bone testing. This study reports some of the first quantitative μCT data of human OI bone, and it suggests compelling possibilities for the future of OI bone assessment.

  18. Effects of a telescopic intramedullary rod for treating patients with osteogenesis imperfecta of the femur

    Science.gov (United States)

    Rosemberg, D. L.; Goiano, E. O.; Akkari, M.; Santili, C.

    2018-01-01

    Abstract Purpose To introduce a new model of telescopic intramedullary rod (TIR), evaluate its effects on treating patients presenting with moderate and severe osteogenesis imperfecta (OI) and to compare the findings with those of other telescopic rods. Methods A total of 21 patients (nine girls and 12 boys; mean age at first operation, 6.6 years, 1.52 to 13.18) who underwent 52 femoral operations were monitored during a mean of 9.96 years (3.39 to 14.54). Patient characteristics, telescoping rod capability and its complications were examined. Results According to the Sillence classification, we investigated one patient with type I, nine with type III and 11 with type IV OI. Revision rates at up to five years (36%) were inferior to those found for the Fassier-Duval rod (46%). The main cause of revision was fracture (15 patients), followed by rod migration (nine), and infection (two). The rod exhibited higher telescopic capacity in boys than girls. Type III most commonly required an operation; the age group with the highest number of procedures was five to ten years. Male migration was the main cause of rod migration. Conclusion The TIR has a satisfactory cost-benefit ratio with less complication rates and low production costs. The TIR is a feasible alternative to the commonly used Fassier-Duval rod. Level of Evidence IV PMID:29456761

  19. Osteogenesis imperfecta type V: Genetic and clinical findings in eleven Chinese patients.

    Science.gov (United States)

    Liu, Yi; Wang, Jiawei; Ma, Doudou; Lv, Fang; Xu, Xiaojie; Xia, Weibo; Jiang, Yan; Wang, Ou; Xing, Xiaoping; Zhou, Peiran; Wang, Jianyi; Yu, Wei; Li, Mei

    2016-11-01

    Osteogenesis imperfecta (OI) type V is a rare inherited disease characterized by multiple fractures, intraosseous membrane calcification, and hypercallus formation. We investigate the causative gene, phenotype and also observe the effects of zoledronic acid in Chinese OI type V patients. The clinical phenotype and causative gene mutation was investigated in eleven patients with type V OI. Patients were given a dose of zoledronic acid 5mg intravenously. Fracture incidence and Z-score of bone mineral density (BMD) were evaluated. Serum levels of biomarkers such as cross linked C-telopeptide of type I collagen (β-CTX) and safety parameters were assessed. The c.-14C>T mutation in the 5' untranslated region of IFITM5 was detected in all patients. The phenotype was largely variable, and no significant correlation of genotype and phenotype was found. After one dose of zoledronic acid infusion, fracture incidence significantly dropped from 2fractures/year before treatment to 0fracture/year after treatment (P=0.01). Z score of lumbar spine BMD elevated from -2.6 to -1.3 (P<0.001). Serum β-CTX level decreased by 50% (P<0.05). No serious adverse event was found. No obvious correlation was found between the genotype and phenotype. Zoledronic acid had significantly skeletal protective effects in OI of type V. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Phenotypic Variability of Osteogenesis Imperfecta Type V Caused by an IFITM5 Mutation

    Science.gov (United States)

    Shapiro, Jay R; Lietman, Caressa; Grover, Monica; Lu, James T; Nagamani, Sandesh CS; Dawson, Brian C; Baldridge, Dustin M; Bainbridge, Matthew N; Cohn, Dan H; Blazo, Maria; Roberts, Timothy T; Brennen, Feng-Shu; Wu, Yimei; Gibbs, Richard A; Melvin, Pamela; Campeau, Philippe M; Lee, Brendan H

    2013-01-01

    In a large cohort of osteogenesis imperfecta type V (OI type V) patients (17 individuals from 12 families), we identified the same mutation in the 5′ untranslated region (5′UTR) of the interferon-induced transmembrane protein 5 (IFITM5) gene by whole exome and Sanger sequencing (IFITM5 c.–14C > T) and provide a detailed description of their phenotype. This mutation leads to the creation of a novel start codon adding five residues to IFITM5 and was recently reported in several other OI type V families. The variability of the phenotype was quite large even within families. Whereas some patients presented with the typical calcification of the forearm interosseous membrane, radial head dislocation and hyperplastic callus (HPC) formation following fractures, others had only some of the typical OI type V findings. Thirteen had calcification of interosseous membranes, 14 had radial head dislocations, 10 had HPC, 9 had long bone bowing, 11 could ambulate without assistance, and 1 had mild unilateral mixed hearing loss. The bone mineral density varied greatly, even within families. Our study thus highlights the phenotypic variability of OI type V caused by the IFITM5 mutation. PMID:23408678

  1. Quantitative changes in human epithelial cancers and osteogenesis imperfecta disease detected using nonlinear multicontrast microscopy

    Science.gov (United States)

    Adur, Javier; Pelegati, Vitor B.; de Thomaz, Andre A.; D'Souza-Li, Lilia; Assunção, Maria do Carmo; Bottcher-Luiz, Fátima; Andrade, Liliana A. L. A.; Cesar, Carlos L.

    2012-08-01

    We show that combined multimodal nonlinear optical (NLO) microscopies, including two-photon excitation fluorescence, second-harmonic generation (SHG), third harmonic generation, and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation during the progression of cancer and osteogenesis imperfecta (OI) disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for different types of human breast cancer, mucinous ovarian tumors, and skin dermis of patients with OI. Using a set of scoring methods (anisotropy, correlation, uniformity, entropy, and lifetime components), we found significant differences in the content, distribution and organization of collagen fibrils in the stroma of breast and ovary as well as in the dermis of skin. We suggest that our results provide a framework for using NLO techniques as a clinical diagnostic tool for human cancer and OI. We further suggest that the SHG and FLIM metrics described could be applied to other connective or epithelial tissue disorders that are characterized by abnormal cells proliferation and collagen assembly.

  2. Gender-dependence of bone structure and properties in adult osteogenesis imperfecta murine model.

    Science.gov (United States)

    Yao, Xiaomei; Carleton, Stephanie M; Kettle, Arin D; Melander, Jennifer; Phillips, Charlotte L; Wang, Yong

    2013-06-01

    Osteogenesis imperfecta (OI) is a dominant skeletal disorder characterized by bone fragility and deformities. Though the oim mouse model has been the most widely studied of the OI models, it has only recently been suggested to exhibit gender-dependent differences in bone mineralization. To characterize the impact of gender on the morphometry/ultra-structure, mechanical properties, and biochemical composition of oim bone on the congenic C57BL/J6 background, 4-month-old oim/oim, +/oim, and wild-type (wt) female and male tibiae were evaluated using micro-computed tomography, three-point bending, and Raman spectroscopy. Dramatic gender differences were evident in both cortical and trabecular bone morphological and geometric parameters. Male mice had inherently more bone and increased moment of inertia than genotype-matched female counterparts with corresponding increases in bone biomechanical strength. The primary influence of gender was structure/geometry in bone growth and mechanical properties, whereas the mineral/matrix composition and hydroxyproline content of bone were influenced primarily by the oim collagen mutation. This study provides evidence of the importance of gender in the evaluation and interpretation of potential therapeutic strategies when using mouse models of OI.

  3. Sclerostin antibody improves skeletal parameters in a Brtl/+ mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Sinder, Benjamin P; Eddy, Mary M; Ominsky, Michael S; Caird, Michelle S; Marini, Joan C; Kozloff, Kenneth M

    2013-01-01

    Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture. Symptoms are most prominent during childhood. Although antiresorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials show improved vertebral parameters but equivocal effects on long-bone fracture rates. New treatments for OI are needed to increase bone mass throughout the skeleton. Sclerostin antibody (Scl-Ab) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI. In this study, Scl-Ab therapy was investigated in mice heterozygous for a typical OI-causing Gly→Cys substitution in col1a1. Two weeks of Scl-Ab successfully stimulated osteoblast bone formation in a knock-in model for moderately severe OI (Brtl/+) and in WT mice, leading to improved bone mass and reduced long-bone fragility. Image-guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl-Ab. These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility. In conclusion, short-term Scl-Ab was successfully anabolic in osteoblasts harboring a typical OI-causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI. Copyright © 2013 American Society for Bone and Mineral Research.

  4. Health outcomes of neonates with osteogenesis imperfecta: a cross-sectional study.

    Science.gov (United States)

    Yimgang, Doris P; Brizola, Evelise; Shapiro, Jay R

    2016-12-01

    To assess at-birth health outcomes of neonates with osteogenesis imperfecta (OI). A total of 53 women who self-reported having had at least one child with OI completed the survey. We evaluated pregnancy length, neonatal intensive care unit (NICU) usage, at-birth complications, and the child's clinical information including OI type, height and weight. Information was gathered on a total of 77 children (60 type I, 4 type III and 13 type IV). Health conditions reported at birth included breech presentation (24%), prematurity (27%), fracture (18%), bone deformity (18%) and respiratory problems (22%). Approximately 31% (n = 24) received NICU care. There was a significant association between younger maternal age, preterm delivery and NICU admission. Our findings suggest that newborns with OI appear to be at high risk of skeletal disorders, preterm delivery and breech presentation. Younger maternal age and preterm delivery seem to be strong predictors of the need for NICU care. Our data suggest that pregnant women with OI younger than 20 years of age may benefit from added clinical supervision in anticipation of adverse effects on their child.

  5. A DSPP Mutation Causing Dentinogenesis Imperfecta and Characterization of the Mutational Effect

    Directory of Open Access Journals (Sweden)

    Sook-Kyung Lee

    2013-01-01

    Full Text Available Mutations in the DSPP gene have been identified in nonsyndromic hereditary dentin defects, but the genotype-phenotype correlations are not fully understood. Recently, it has been demonstrated that the mutations of DSPP affecting the IPV leader sequence result in mutant DSPP retention in rough endoplasmic reticulum (ER. In this study, we identified a Korean family with dentinogenesis imperfecta type III. To identify the disease causing mutation in this family, we performed mutational analysis based on candidate gene sequencing. Exons and exon-intron boundaries of DSPP gene were sequenced, and the effects of the identified mutation on the pre-mRNA splicing and protein secretion were investigated. Candidate gene sequencing revealed a mutation (c.50C > T, p.P17L in exon 2 of the DSPP gene. The splicing assay showed that the mutation did not influence pre-mRNA splicing. However, the mutation interfered with protein secretion and resulted in the mutant protein remaining largely in the ER. These results suggest that the mutation affects ER-to-Golgi apparatus export and results in the reduction of secreted DSPP and ER overload. This may induce cell stress and damage processing and/or transport of dentin matrix proteins or other critical proteins.

  6. Introduction of a new standardized assessment score of spine morphology in osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Koerber, F.; Schulze Uphoff, U.; Koerber, S.; Maintz, D. [Koeln Univ. (Germany). Dept. of Radiology; Schoenau, E.; Semler, O. [Koeln Univ. (Germany). Children' s Hospital

    2012-08-15

    Purpose: Osteogenesis imperfecta (OI) is a rare hereditary disease leading to multiple bone deformities and fractures. In the absence of causal therapy, a symptomatic approach is based on treatment with bisphosphonates and physiotherapy. The clinical and radiological manifestations vary. Therefore, standardization and quantification for an objective comparison, especially during therapy, are required. In this paper, radiological changes of the spine are quantified according to their clinical relevance to define a scoring system that transfers the morphological changes into a single value representing the severity of the disease. Materials and Methods: 268 lateral spine X-rays of 95 patients with OI (median age 5.6 years) were assessed. The findings were classified based on their clinical relevance. Results: The three criteria, vertebral compression, thoracolumbar kyphosis and deformity type, were quantified in a new grading system. Based on this, a 'severity classification' (1 to 5) was defined with implications for diagnostics and treatment. A mathematical formula that takes into account the three criteria and their correlations to clinical relevance, resulting in a 'severity score', was developed. Conclusion: 'Severity classification' and 'severity score' introduce a new concept for a standardized evaluation of spine X-rays in patients with OI. For both scientific and routine purposes, it provides the user with a simple and easy-to-handle tool for assessing and comparing different stages of severity prior to and during therapy with detailed accuracy. (orig.)

  7. Dentin phosphoprotein gene locus is not associated with dentinogenesis imperfecta types II and III

    Energy Technology Data Exchange (ETDEWEB)

    MacDougall, M.; Zeichner-David, M.; Davis, A.; Slavkin, H. (Univ. of Southern California, Los Angeles (United States)); Murray, J. (Univ. of Iowa, Iowa City (United States)); Crall, M. (Ohio State Univ., Columbus (United States))

    1992-01-01

    Dentinogenesis imperfecta (DGI) is an autosomal dominant inherited dental disease which affects dentin production and mineralization. Genetic linkage studies have been performed on several multigeneration informative kindreds. These studies determined linkage between DGI types II and III and group-specific component (vitamin D-binding protein). This gene locus has been localized to the long arm of human chromosome 4 in the region 4q11-q21. Although this disease has been mapped to chromosome 4, the defective gene product is yet to be determined. Biochemical studies have suggested abnormal levels of dentin phosphoprotein (DPP) associated with DGI type II. This highly acidic protein is the major noncollagenous component of dentin, being solely expressed by the ectomesenchymal derived odontoblast cells of the tooth. The purpose of the present study was to establish whether DPP is associated with DGI types II and III, by using molecular biology techniques. The results indicated that DPP is not localized to any region of human chromosome 4, thus suggesting that the DPP gene is not directly associated with DGI type II or DGI type III. The data do not exclude the possibility that other proteins associated with DPP posttranslational modifications might be responsible for this genetic disease.

  8. Dental panoramic indices and fractal dimension measurements in osteogenesis imperfecta children under pamidronate treatment.

    Science.gov (United States)

    Apolinário, Ana C; Sindeaux, Rafael; de Souza Figueiredo, Paulo T; Guimarães, Ana T B; Acevedo, Ana C; Castro, Luiz C; de Paula, Ana P; de Paula, Lilian M; de Melo, Nilce S; Leite, André F

    2016-01-01

    To verify radiomorphometric indices and fractal dimension (FD) in dental panoramic radiographs (DPRs) of children with different types of osteogenesis imperfecta (OI) and also to verify the effect of pamidronate (PAM) treatment in such panoramic analyses. In this retrospective study, 197 DPRs of 62 children with OI Types I, III and IV who were in treatment with a comparable dosage of intravenous PAM were selected. The mandibular cortical width (MCW), mandibular cortical index, visual estimation of the cortical width and FD of three standardized trabecular and cortical mandibular regions of interest were obtained from the radiographs. Factorial analysis of variance and Fisher test were used to compare FD and MCW measurements in children with different types of OI for different PAM cycles. Children with all types of OI have thinner and more porous mandibular cortices at the beginning of treatment. There were significant differences between MCW and FD of the cortical bone, regarding different types of OI and number of PAM cycles (p = 0.037 and p = 0.044, respectively). FD measurements of the trabecular bone were not statistically different among OI types nor were PAM cycles (p > 0.05). Children with OI presented cortical bone alterations after PAM treatment. Both MCW and the FD of the cortical bone were higher in children with OI after PAM treatment. It is argued that cortical bone should be considered for analyzing patients with OI, as well as to monitor the progress of PAM treatment.

  9. Multiparametric Classification of Skin from Osteogenesis Imperfecta Patients and Controls by Quantitative Magnetic Resonance Microimaging.

    Science.gov (United States)

    Ashinsky, Beth G; Fishbein, Kenneth W; Carter, Erin M; Lin, Ping-Chang; Pleshko, Nancy; Raggio, Cathleen L; Spencer, Richard G

    2016-01-01

    The purpose of this study is to evaluate the ability of quantitative magnetic resonance imaging (MRI) to discriminate between skin biopsies from individuals with osteogenesis imperfecta (OI) and skin biopsies from individuals without OI. Skin biopsies from nine controls (unaffected) and nine OI patients were imaged to generate maps of five separate MR parameters, T1, T2, km, MTR and ADC. Parameter values were calculated over the dermal region and used for univariate and multiparametric classification analysis. A substantial degree of overlap of individual MR parameters was observed between control and OI groups, which limited the sensitivity and specificity of univariate classification. Classification accuracies ranging between 39% and 67% were found depending on the variable of investigation, with T2 yielding the best accuracy of 67%. When several MR parameters were considered simultaneously in a multivariate analysis, the classification accuracies improved up to 89% for specific combinations, including the combination of T2 and km. These results indicate that multiparametric classification by quantitative MRI is able to detect differences between the skin of OI patients and of unaffected individuals, which motivates further study of quantitative MRI for the clinical diagnosis of OI.

  10. Mechanical and mineral properties of osteogenesis imperfecta human bones at the tissue level.

    Science.gov (United States)

    Imbert, Laurianne; Aurégan, Jean-Charles; Pernelle, Kélig; Hoc, Thierry

    2014-08-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by an increase in bone fragility on the macroscopic scale, but few data are available to describe the mechanisms involved on the tissue scale and the possible correlations between these scales. To better understand the effects of OI on the properties of human bone, we studied the mechanical and chemical properties of eight bone samples from children suffering from OI and compared them to the properties of three controls. High-resolution computed tomography, nanoindentation and Raman microspectroscopy were used to assess those properties. A higher tissue mineral density was found for OI bone (1.131 gHA/cm3 vs. 1.032 gHA/cm3, p=0.032), along with a lower Young's modulus (17.6 GPa vs. 20.5 GPa, p=0.024). Obviously, the mutation-induced collagen defects alter the collagen matrix, thereby affecting the mineralization. Raman spectroscopy showed that the mineral-to-matrix ratio was higher in the OI samples, while the crystallinity was lower, suggesting that the mineral crystals were smaller but more abundant in the case of OI. This change in crystal size, distribution and composition contributes to the observed decrease in mechanical strength. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. A missense mutation in the SERPINH1 gene in Dachshunds with osteogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Cord Drögemüller

    2009-07-01

    Full Text Available Osteogenesis imperfecta (OI is a hereditary disease occurring in humans and dogs. It is characterized by extremely fragile bones and teeth. Most human and some canine OI cases are caused by mutations in the COL1A1 and COL1A2 genes encoding the subunits of collagen I. Recently, mutations in the CRTAP and LEPRE1 genes were found to cause some rare forms of human OI. Many OI cases exist where the causative mutation has not yet been found. We investigated Dachshunds with an autosomal recessive form of OI. Genotyping only five affected dogs on the 50 k canine SNP chip allowed us to localize the causative mutation to a 5.82 Mb interval on chromosome 21 by homozygosity mapping. Haplotype analysis of five additional carriers narrowed the interval further down to 4.74 Mb. The SERPINH1 gene is located within this interval and encodes an essential chaperone involved in the correct folding of the collagen triple helix. Therefore, we considered SERPINH1 a positional and functional candidate gene and performed mutation analysis in affected and control Dachshunds. A missense mutation (c.977C>T, p.L326P located in an evolutionary conserved domain was perfectly associated with the OI phenotype. We thus have identified a candidate causative mutation for OI in Dachshunds and identified a fifth OI gene.

  12. A fracture risk assessment model of the femur in children with osteogenesis imperfecta (OI) during gait.

    Science.gov (United States)

    Fritz, Jessica M; Guan, Yabo; Wang, Mei; Smith, Peter A; Harris, Gerald F

    2009-11-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder characterized by skeletal deformities and increased bone fragility. There is currently no established clinical method for quantifying fracture risk in OI patients. This study begins the development of a patient-specific model for femur fracture risk assessment and prediction based on individuals' gait analysis data, bone geometry from imaging and material properties from nanoindentation (Young's modulus=19 GPa, Poisson's ratio=0.3). Finite element models of the femur were developed to assess fracture risk of the femur in a pediatric patient with OI type I. Kinetic data from clinical gait analysis was used to prescribe loading conditions on the femoral head and condyles along with muscle forces on the bone's surface. von Mises stresses were analyzed against a fracture strength of 115 MPa. The patient with OI whose femur was modeled showed no risk of femoral fracture during normal gait. The highest stress levels occurred during the mid-stance and loading responses phases of gait. The location of high stress migrated throughout the femoral diaphysis across the gait cycle. Maximum femoral stress levels occurred during the gait cycle phases associated with the highest loading. The fracture risk (fracture strength/von Mises stress), however, was low. This study provides a relevant method for combining functional activity, material property and analytical methods to improve patient monitoring.

  13. EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta.

    Science.gov (United States)

    van Dijk, Fleur S; Byers, Peter H; Dalgleish, Raymond; Malfait, Fransiska; Maugeri, Alessandra; Rohrbach, Marianne; Symoens, Sofie; Sistermans, Erik A; Pals, Gerard

    2012-01-01

    Osteogenesis imperfecta (OI) comprises a group of inherited disorders characterized by bone fragility and increased susceptibility to fractures. Historically, the laboratory confirmation of the diagnosis OI rested on cultured dermal fibroblasts to identify decreased or abnormal production of abnormal type I (pro)collagen molecules, measured by gel electrophoresis. With the discovery of COL1A1 and COL1A2 gene variants as a cause of OI, sequence analysis of these genes was added to the diagnostic process. Nowadays, OI is known to be genetically heterogeneous. About 90% of individuals with OI are heterozygous for causative variants in the COL1A1 and COL1A2 genes. The majority of remaining affected individuals have recessively inherited forms of OI with the causative variants in the more recently discovered genes CRTAP, FKBP10, LEPRE1,PLOD2, PPIB, SERPINF1, SERPINH1 and SP7, or in other yet undiscovered genes. These advances in the molecular genetic diagnosis of OI prompted us to develop new guidelines for molecular testing and reporting of results in which we take into account that testing is also used to 'exclude' OI when there is suspicion of non-accidental injury. Diagnostic flow, methods and reporting scenarios were discussed during an international workshop with 17 clinicians and scientists from 11 countries and converged in these best practice guidelines for the laboratory diagnosis of OI.

  14. Prediction on fracture risk of femur with Osteogenesis Imperfecta using finite element models: Preliminary study

    Science.gov (United States)

    Wanna, S. B. C.; Basaruddin, K. S.; Mat Som, M. H.; Mohamad Hashim, M. S.; Daud, R.; Majid, M. S. Abdul; Sulaiman, A. R.

    2017-10-01

    Osteogenesis imperfecta (OI) is a genetic disease which affecting the bone geometry. In a severe case, this disease can cause death to patients. The main issue of this disease is the prediction on bone fracture by the orthopaedic surgeons. The resistance of the bone to withstand the force before the bones fracture often become the main concern. Therefore, the objective of the present preliminary study was to investigate the fracture risk associated with OI bone, particularly in femur, when subjected to the self-weight. Finite element (FEA) was employed to reconstruct the OI bone model and analyse the mechanical stress response of femur before it fractures. Ten deformed models with different severity of OI bones were developed and the force that represents patient self-weight was applied to the reconstructed models in static analysis. Stress and fracture risk were observed and analysed throughout the simulation. None of the deformed model were observed experienced fracture. The fracture risk increased with increased severity of the deformed bone. The results showed that all deformed femur models were able to bear the force without experienced fracture when subjected to only the self-weight.

  15. Introduction of a new standardized assessment score of spine morphology in osteogenesis imperfecta

    International Nuclear Information System (INIS)

    Koerber, F.; Schulze Uphoff, U.; Koerber, S.; Maintz, D.; Schoenau, E.; Semler, O.

    2012-01-01

    Purpose: Osteogenesis imperfecta (OI) is a rare hereditary disease leading to multiple bone deformities and fractures. In the absence of causal therapy, a symptomatic approach is based on treatment with bisphosphonates and physiotherapy. The clinical and radiological manifestations vary. Therefore, standardization and quantification for an objective comparison, especially during therapy, are required. In this paper, radiological changes of the spine are quantified according to their clinical relevance to define a scoring system that transfers the morphological changes into a single value representing the severity of the disease. Materials and Methods: 268 lateral spine X-rays of 95 patients with OI (median age 5.6 years) were assessed. The findings were classified based on their clinical relevance. Results: The three criteria, vertebral compression, thoracolumbar kyphosis and deformity type, were quantified in a new grading system. Based on this, a 'severity classification' (1 to 5) was defined with implications for diagnostics and treatment. A mathematical formula that takes into account the three criteria and their correlations to clinical relevance, resulting in a 'severity score', was developed. Conclusion: 'Severity classification' and 'severity score' introduce a new concept for a standardized evaluation of spine X-rays in patients with OI. For both scientific and routine purposes, it provides the user with a simple and easy-to-handle tool for assessing and comparing different stages of severity prior to and during therapy with detailed accuracy. (orig.)

  16. Structure–mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model

    Science.gov (United States)

    Andriotis, O. G.; Chang, S. W.; Vanleene, M.; Howarth, P. H.; Davies, D. E.; Shefelbine, S. J.; Buehler, M. J.; Thurner, P. J.

    2015-01-01

    The collagen molecule, which is the building block of collagen fibrils, is a triple helix of two α1(I) chains and one α2(I) chain. However, in the severe mouse model of osteogenesis imperfecta (OIM), deletion of the COL1A2 gene results in the substitution of the α2(I) chain by one α1(I) chain. As this substitution severely impairs the structure and mechanics of collagen-rich tissues at the tissue and organ level, the main aim of this study was to investigate how the structure and mechanics are altered in OIM collagen fibrils. Comparing results from atomic force microscopy imaging and cantilever-based nanoindentation on collagen fibrils from OIM and wild-type (WT) animals, we found a 33% lower indentation modulus in OIM when air-dried (bound water present) and an almost fivefold higher indentation modulus in OIM collagen fibrils when fully hydrated (bound and unbound water present) in phosphate-buffered saline solution (PBS) compared with WT collagen fibrils. These mechanical changes were accompanied by an impaired swelling upon hydration within PBS. Our experimental and atomistic simulation results show how the structure and mechanics are altered at the individual collagen fibril level as a result of collagen gene mutation in OIM. We envisage that the combination of experimental and modelling approaches could allow mechanical phenotyping at the collagen fibril level of virtually any alteration of collagen structure or chemistry. PMID:26468064

  17. Mutation analysis of the COL1A1 and COL1A2 genes in Vietnamese patients with osteogenesis imperfecta.

    Science.gov (United States)

    Ho Duy, Binh; Zhytnik, Lidiia; Maasalu, Katre; Kändla, Ivo; Prans, Ele; Reimann, Ene; Märtson, Aare; Kõks, Sulev

    2016-08-12

    The genetics of osteogenesis imperfecta (OI) have not been studied in a Vietnamese population before. We performed mutational analysis of the COL1A1 and COL1A2 genes in 91 unrelated OI patients of Vietnamese origin. We then systematically characterized the mutation profiles of these two genes which are most commonly related to OI. Genomic DNA was extracted from EDTA-preserved blood according to standard high-salt extraction methods. Sequence analysis and pathogenic variant identification was performed with Mutation Surveyor DNA variant analysis software. Prediction of the pathogenicity of mutations was conducted using Alamut Visual software. The presence of variants was checked against Dalgleish's osteogenesis imperfecta mutation database. The sample consisted of 91 unrelated osteogenesis imperfecta patients. We identified 54 patients with COL1A1/2 pathogenic variants; 33 with COL1A1 and 21 with COL1A2. Two patients had multiple pathogenic variants. Seventeen novel COL1A1 and 10 novel COL1A2 variants were identified. The majority of identified COL1A1/2 pathogenic variants occurred in a glycine substitution (36/56, 64.3 %), usually serine (23/36, 63.9 %). We found two pathogenic variants of the COL1A1 gene c.2461G > A (p.Gly821Ser) in four unrelated patients and one, c.2005G > A (p.Ala669Thr), in two unrelated patients. Our data showed a lower number of collagen OI pathogenic variants in Vietnamese patients compared to reported rates for Asian populations. The OI mutational profile of the Vietnamese population is unique and related to the presence of a high number of recessive mutations in non-collagenous OI genes. Further analysis of OI patients negative for collagen mutations, is required.

  18. Associação entre artrite idiopática juvenil e osteogenesis imperfecta: relato de caso

    Directory of Open Access Journals (Sweden)

    Blanca Elena Rios Gomes Bica

    2013-12-01

    Full Text Available Os autores relatam o caso de uma paciente de 53 anos que apresenta uma rara associação entre artrite idiopática juvenil (AIJ e osteogenesis imperfecta (OI, com acometimento poliarticular, incluindo a articulação temporomandibular. Apresentam uma revisão da literatura e uma discussão dos aspectos radiológicos do acometimento da referida articulação. Não foram encontrados relatos de casos com semelhante associação de doenças na literatura especializada.

  19. Deep tissue single cell MSC ablation using a fiber laser source to evaluate therapeutic potential in osteogenesis imperfecta

    Science.gov (United States)

    Tehrani, Kayvan F.; Pendleton, Emily G.; Lin, Charles P.; Mortensen, Luke J.

    2016-04-01

    Osteogenesis imperfecta (OI) is a currently uncurable disease where a mutation in collagen type I yields brittle bones. One potential therapy is transplantation of mesenchymal stem cells (MSCs), but controlling and enhancing transplanted cell survival has proven challenging. Therefore, we use a 2- photon imaging system to study individual transplanted cells in the living bone marrow. We ablated cells deep in the bone marrow and observed minimal collateral damage to surrounding tissue. Future work will evaluate the local impact of transplanted MSCs on bone deposition in vivo.

  20. Amelogenésis imperfecta: Criterios de clasificación y aspectos genéticos

    OpenAIRE

    Gonzales-Pinedo, Clara O.; Cirujano - Dentista; Perona-Miguel del Priego, Guido; Docente del Departamento Académico de Estomatología del Niño y del Adolescente. Facultad de Estomatología. Universidad Peruana Cayetano Heredia. Lima.

    2014-01-01

    La amelogénesis imperfecta es una alteración del esmalte que se puede presentar tanto en dentición decidua como permanente con diversas consecuencias negativas para los pacientes.La presente revisión describe los criterios diagnósticos, clasificación, etiología, casos esporádicos en los que se ha relacionado con otras alteraciones clínicas o enfermedades sistémicas, y su tratamiento; enfatizando la etiología y clasificación de esta alteración puesto que son las áreas en las que se han realiza...

  1. Skeletal phenotypes in adult patients with osteogenesis imperfecta-correlations with COL1A1/COL1A2 genotype and collagen structure

    DEFF Research Database (Denmark)

    Hald, Jannie Dahl; Folkestad, L; Harsløf, T

    2016-01-01

    Osteogenesis imperfecta (OI) is characterized by a high fracture rate and great heterogeneity. This cross-sectional study presents skeletal investigations and protein analyses in 85 adult OI patients. We find significant differences in bone mass, architecture, and fracture rate that correlate well...

  2. Osteogenesis imperfecta - iconographic study of two cases and review of the literature; Osteogenese imperfeita - revisao da literatura e iconografia baseada em dois casos

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Ricardo Pires de; Fernandes, Cintia; Hilario, Marcelo Cobra; Barros, Wagner Moraes; Soares, Aldemir Humberto [Hospital Heliopolis, Sao Paulo, SP (Brazil)

    1996-07-01

    The authors present a literature review about osteogenesis imperfecta, a disease that leads to bone fragility and low height patterns caused by an abnormality of the collagen synthesis. The iconographic study is based on two cases of the tarda type. (author) 9 refs., 3 figs.

  3. Prevalência de defeitos de esmalte em indivíduos portadores de fissuras labiopalatinas da Paraíba, Brasil Prevalencia de amelogénesis imperfecta en pacientes con labio y paladar fisurados en Paraíba, Brasil Prevalence of defective amelogenesis in patients with palatoschisis in Paraíba, Brazil

    Directory of Open Access Journals (Sweden)

    Rosa Helena Wanderley Lacerda

    2012-03-01

    Full Text Available Os defeitos de esmalte estão entre as alterações que acometem os indivíduos portadores de fissuras labiopalatinas. O propósito do presente estudo foi descrever a prevalência de defeitos de esmalte em indivíduos portadores de fissuras, bem como a sua distribuição quanto ao tipo de fissura e lado fissurado, nos pacientes que procuraram o serviço de referência em ortodontia no atendimento de fissurados da Paraíba, Brasil. Para tanto, este estudo caracterizou-se por ser do tipo transversal e observacional, adotando como estratégia de coleta de dados o exame clínico em 76 indivíduos portadores de fissuras pós e transforame incisivo unilateral ou bilateral, de ambos os sexos, com média de idade de 13,3 anos. O exame foi realizado nos dentes incisivos e caninos superiores, por dois examinadores previamente treinados (kappa= 0,89. Os pacientes incluídos foram todos que estavam em atendimento no período de janeiro a junho de 2011 em que as faces vestibulares dos dentes a serem examinados permitissem a avaliação clínica. Foram excluídos os que apresentavam outras deformidades associadas e que não tivessem sido submetidos às cirurgias primárias. Os dados foram submetidos à estatística descritiva e ao teste estatístico qui-quadrado, sendo significativo ao nível de 5 %. Houve predominância do gênero masculino (57,9 % e da fissura transforame incisiva unilateral esquerda (40,8 %. Em relação ao defeito de esmalte, o dente mais acometido foi o incisivo central, a maioria dos examinados apresentou opacidade difusa (14,9 %, seguida pela presença de opacidade demarcada (13,15 % e opacidade mais hipoplasia (10,9 % e houve diferença estatística significativa (pLos defectos en el esmalte son algunos de los cambios que afectan a las personas con labio y paladar fisurados. El propósito de este estudio fue describir la prevalencia de defectos del esmalte con fisura labial y palatina, así como su distribución por tipo de fisura, en los pacientes que asistieron al servicio de ortodoncia de Paraíba, Brasil. Se realizó un estudio transversal y observacional donde se recolectaron datos del examen clínico en 76 pacientes con fisura post foramen, trans foramen incisivo unilateral o bilateral, de ambos sexos y con una edad media de 13,3 años. El examen fue realizado en los dientes incisivos y caninos superiores, por dos examinadores previamente capacitados (kappa= 0,89. Los pacientes incluidos fueron los que asistieron al servicio durante el periodo de enero a junio de 2011, en los que las superficies vestibulares de los dientes que se examinaron permitieron una evaluación clínica. Se excluyeron aquellos con malformaciones y que no habían sido sometidos a cirugía primaria. Los datos fueron sometidos a estadística descriptiva y chi-cuadrado con una significación de 5 %. El sexo masculino representó el 57,9 % y la fisura unilateral izquierda fue de un 40,8 %. En relación con defectos en el esmalte, el diente más afectado fue el incisivo central, mostraron opacidad difusa para un 14,9 %, seguido por la presencia de opacidad limitada para un 13,15 % e hipoplasia con un 10,9 %. Se encontraron diferencias estadísticamente significativas (pThe enamel defects are some of the changes affecting persons with palatoschisis. The aim or present paper was to describe the prevalence of enamel defects with labial and palatine fissure, as well as its distribution by type of fissure in patients came to Orthodontics service of Paraíba, Brazil. A cross-sectional and observational study was conducted to collect data from the postmortem physical examination of 76 patients with palatoschisis through the unilateral and bilateral incisor foramen, of both sexes and a mean age of 13.3 years. The examination was performed in the upper incisor and canines by two examiners previously trained (kappa= 0.89. Patients included were those came to service from January to June, 2011, where the vestibular surfaces of teeth allowed a clinical assessment. Those with malformations and no primary surgery were excluded. Data were analyzed by descriptive statistics and Chi² test with a significance of 5 %. The male sex accounted for 57.9 % and the left unilateral fissure was of 40.8 %. In relation to enamel defects, the more involved tooth was the central incisor and a diffuse opacity for a 14.9 % followed by the presence of limited opacity for a 13.15 % and hypoplasia for a 10.9 %. There were statistically significant differences (p< 0.00001 between fissure and the contralateral side. Results showed the high frequency of enamel defects in the study patients, mainly in bilateral cases and in teeth adjacent to fissure side.

  4. A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.

    Science.gov (United States)

    Patel, R M; Nagamani, S C S; Cuthbertson, D; Campeau, P M; Krischer, J P; Shapiro, J R; Steiner, R D; Smith, P A; Bober, M B; Byers, P H; Pepin, M; Durigova, M; Glorieux, F H; Rauch, F; Lee, B H; Hart, T; Sutton, V R

    2015-02-01

    Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Comparative X-ray morphometry of prenatal osteogenesis imperfecta type 2 and thanatophoric dysplasia: a contribution to prenatal differential diagnosis.

    Science.gov (United States)

    Bondioni, Maria Pia; Pazzaglia, Ugo Ernesto; Izzi, Claudia; Di Gaetano, Giuseppe; Laffranchi, Francesco; Baldi, Maurizia; Prefumo, Federico

    2017-11-01

    The purpose of the paper was to assess the morphometric parameters to improve the specificity of the ultrasound (US) signs for the early differential diagnosis between two lethal dysplasias, as thanatophoric dysplasia (TD) and osteogenesis imperfecta type 2 (OI-2). The diaphyseal length and the bowed shape of long bones associated with vertebral body dimension assessment were investigated in a group of 14 pregnancy terminations carried out in the time period 2007-2013. The definitive diagnosis was established after pregnancy termination by means of skeletal standardized X-rays, histopathology and gene analysis. TD and OI-2 long bones were significantly shorter than controls. No significant differences were observed between the two dysplasias. The bowing angle was higher in OI-2; a true angulation or eventually axial displacement was present only in the latter. Furthermore, they did not show any evidence of vertebral collapse. The thanatophoric dysplasia presented less bowed long bones, and never true angulation. The spine was steadily characterized by flattened anterior vertebral bodies. Long bone shortening is not a sufficient and accurate sign for early sonographic differential diagnosis between TD and OI-2. Angled diaphysis, axial diaphyseal displacement and a conserved vertebral body height in the prenatal period support the diagnosis of osteogenesis imperfecta type 2, while moderately regular bowed diaphysis associated with platyspondyly that of thanatophoric dysplasia.

  6. A Cross-sectional Multicenter Study of Osteogenesis Imperfecta in North America – Results from the Linked Clinical Research Centers

    Science.gov (United States)

    Patel, Ronak M; Nagamani, Sandesh CS; Cuthbertson, David; Campeau, Philippe M; Krischer, Jeffrey P; Shapiro, Jay R; Steiner, Robert D; Smith, Peter A; Bober, Michael B; Byers, Peter H; Pepin, Melanie; Durigova, Michaela; Glorieux, Francis H; Rauch, Frank; Lee, Brendan H; Smith, Tracy; Sutton, V. Reid

    2017-01-01

    Osteogenesis Imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n=544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean LS aBMD was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answer questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of “phenotypic expansion” driven by next-generation sequencing. PMID:24754836

  7. A novel homozygous variant in SERPINH1 associated with a severe, lethal presentation of osteogenesis imperfecta with hydranencephaly.

    Science.gov (United States)

    Marshall, Charlotte; Lopez, Jaime; Crookes, Laura; Pollitt, Rebecca C; Balasubramanian, Meena

    2016-12-20

    Osteogenesis imperfecta (OI) is a genetic disorder characterised by low bone mineral density resulting in fractures. 85-90% of patients with OI carry a variant in the type 1 collagen genes, COL1A1 and COL1A2, which follows an autosomal dominant pattern of inheritance. However, within the last two decades, there have been growing number of variants identified in genes that follow an autosomal recessive pattern of inheritance. Our proband is a child born in Mexico with multiple fractures of ribs, minimal calvarial mineralisation, platyspondyly, marked compression and deformed long bones. He also presented with significant hydranencephaly, requiring ventilatory support from birth, and died at 8days of age. A homozygous c.338_357delins22 variant in exon 2 of SERPINH1 was identified. This gene encodes heat shock protein 47, a collagen-specific chaperone which binds to the procollagen triple helix and is responsible for collagen stabilisation in the endoplasmic reticulum. There is minimal literature on the mechanism of action for variants in SERPINH1 resulting in osteogenesis imperfecta. Here we discuss this rare, previously unreported variant, and expand on the phenotypic presentation of this novel variant resulting in a severe, lethal phenotype of OI in association with hydranencephaly. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Rib cage deformities alter respiratory muscle action and chest wall function in patients with severe osteogenesis imperfecta.

    Science.gov (United States)

    LoMauro, Antonella; Pochintesta, Simona; Romei, Marianna; D'Angelo, Maria Grazia; Pedotti, Antonio; Turconi, Anna Carla; Aliverti, Andrea

    2012-01-01

    Osteogenesis imperfecta (OI) is an inherited connective tissue disorder characterized by bone fragility, multiple fractures and significant chest wall deformities. Cardiopulmonary insufficiency is the leading cause of death in these patients. Seven patients with severe OI type III, 15 with moderate OI type IV and 26 healthy subjects were studied. In addition to standard spirometry, rib cage geometry, breathing pattern and regional chest wall volume changes at rest in seated and supine position were assessed by opto-electronic plethysmography to investigate if structural modifications of the rib cage in OI have consequences on ventilatory pattern. One-way or two-way analysis of variance was performed to compare the results between the three groups and the two postures. Both OI type III and IV patients showed reduced FVC and FEV(1) compared to predicted values, on condition that updated reference equations are considered. In both positions, ventilation was lower in OI patients than control because of lower tidal volume (pfunction was normal, OI type III patients were characterized by reduced (prespiratory pattern of Osteogenesis Imperfecta is closely related to the severity of the disease and to the sternal deformities. Pectus carinatum characterizes OI type III patients and alters respiratory muscles coordination, leading to chest wall and rib cage distortions and an inefficient ventilator pattern. OI type IV is characterized by lower alterations in the respiratory function. These findings suggest that functional assessment and treatment of OI should be differentiated in these two forms of the disease.

  9. Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta.

    Science.gov (United States)

    Becker, Jutta; Semler, Oliver; Gilissen, Christian; Li, Yun; Bolz, Hanno Jörn; Giunta, Cecilia; Bergmann, Carsten; Rohrbach, Marianne; Koerber, Friederike; Zimmermann, Katharina; de Vries, Petra; Wirth, Brunhilde; Schoenau, Eckhard; Wollnik, Bernd; Veltman, Joris A; Hoischen, Alexander; Netzer, Christian

    2011-03-11

    Osteogenesis imperfecta (OI) is a heterogeneous genetic disorder characterized by bone fragility and susceptibility to fractures after minimal trauma. After mutations in all known OI genes had been excluded by Sanger sequencing, we applied next-generation sequencing to analyze the exome of a single individual who has a severe form of the disease and whose parents are second cousins. A total of 26,922 variations from the human reference genome sequence were subjected to several filtering steps. In addition, we extracted the genotypes of all dbSNP130-annotated SNPs from the exome sequencing data and used these 299,494 genotypes as markers for the genome-wide identification of homozygous regions. A single homozygous truncating mutation, affecting SERPINF1 on chromosome 17p13.3, that was embedded into a homozygous stretch of 2.99 Mb remained. The mutation was also homozygous in the affected brother of the index patient. Subsequently, we identified homozygosity for two different truncating SERPINF1 mutations in two unrelated patients with OI and parental consanguinity. All four individuals with SERPINF1 mutations have severe OI. Fractures of long bones and severe vertebral compression fractures with resulting deformities were observed as early as the first year of life in these individuals. Collagen analyses with cultured dermal fibroblasts displayed no evidence for impaired collagen folding, posttranslational modification, or secretion. SERPINF1 encodes pigment epithelium-derived factor (PEDF), a secreted glycoprotein of the serpin superfamily. PEDF is a multifunctional protein and one of the strongest inhibitors of angiogenesis currently known in humans. Our data provide genetic evidence for PEDF involvement in human bone homeostasis. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. Bone Collagen: New Clues to its Mineralization Mechanism From Recessive Osteogenesis Imperfecta

    Science.gov (United States)

    Eyre, David R.; Ann Weis, Mary

    2013-01-01

    Until 2006 the only mutations known to cause osteogenesis imperfecta (OI) were in the two genes coding for type I collagen chains. These dominant mutations affecting the expression or primary sequence of collagen α1(I) and α2(I) chains account for over 90% of OI cases. Since then a growing list of mutant genes causing the 5–10% of recessive cases has rapidly emerged. They include CRTAP, LEPRE1 and PPIB, which encode three proteins forming the prolyl 3-hydroxylase complex; PLOD2 and FKBP10, which encode respectively lysyl hydroxylase 2 and a foldase required for its activity in forming mature cross-links in bone collagen; SERPIN H1, which encodes the collagen chaperone HSP47; SERPIN F1, which encodes pigment epithelium-derived factor required for osteoid mineralization; and BMP1, which encodes the type I procollagen C-propeptidase. All cause fragile bone in infancy, which can include over-mineralization or under-mineralization defects as well as abnormal collagen post-translational modifications. Consistently both dominant and recessive variants lead to abnormal cross-linking chemistry in bone collagen. These recent discoveries strengthen the potential for a common pathogenic mechanism of misassembled collagen fibrils. Of the new genes identified, eight encode proteins required for collagen post-translational modification, chaperoning of newly synthesized collagen chains into native molecules or transport through the endoplasmic reticulum and Golgi for polymerization, cross-linking and mineralization. In reviewing these findings, we conclude that a common theme is emerging in the pathogenesis of brittle bone disease of mishandled collagen assembly with important insights on post-translational features of bone collagen that have evolved to optimize it as a biomineral template. PMID:23508630

  11. The effect of SERPINF1 in-frame mutations in osteogenesis imperfecta type VI.

    Science.gov (United States)

    Al-Jallad, Hadil; Palomo, Telma; Roughley, Peter; Glorieux, Francis H; McKee, Marc D; Moffatt, Pierre; Rauch, Frank

    2015-07-01

    Osteogenesis imperfecta type VI is caused by mutations in SERPINF1, which codes for pigment-epithelium derived factor (PEDF). Most of the reported SERPINF1 mutations lead to premature termination codons, but three in-frame insertion or deletion mutations have also been reported. It is not clear how such in-frame mutations lead to OI type VI. In the present study we therefore investigated how SERPINF1 in-frame mutations affect the intracellular localization and secretion of PEDF. Skin fibroblasts affected by SERPINF1 in-frame mutations transcribed SERPINF1 at slightly reduced levels but secretion of PEDF was markedly diminished. Two deletions (p.F277del and the deletion of SERPINF1 exon 5) were associated with retention of PEDF in the endoplasmic reticulum and a stress response in osteoblastic cells. A recurrent in-frame duplication of three amino acids (p.Ala91_Ser93dup) appeared to lead to intracellular degradation but no retention in the endoplasmic reticulum or stress response. Immunofluorescence imaging in transiently transfected osteoblastic MC3T3-E1 cells suggested that PEDF affected by in-frame mutations was not transported along the secretory pathway. MC3T3-E1 osteoblasts stably overexpressing SERPINF1 with the p.Ala91_Ser93dup mutation had decreased collagen type I deposition and mineralization. Thus, the assessed homozygous in-frame deletions or insertions lead to retention or degradation within cellular compartments and thereby interfere with PEDF secretion. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Strontium Ranelate Reduces the Fracture Incidence in a Growing Mouse Model of Osteogenesis Imperfecta.

    Science.gov (United States)

    Shi, Changgui; Hu, Bo; Guo, Lei; Cao, Peng; Tian, Ye; Ma, Jun; Chen, Yuanyuan; Wu, Huiqiao; Hu, Jinquan; Deng, Lianfu; Zhang, Ying; Yuan, Wen

    2016-05-01

    Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by brittle bones with increased fracture risk. Although current treatment options to improve bone strength in OI focus on antiresorptive bisphosphonates, controlled clinical trials suggest they have an equivocal effect on reducing fracture risk. Strontium ranelate (SrR) is a promising therapy with a dual mode of action that is capable of simultaneously maintaining bone formation and reducing bone resorption, and may be beneficial for the treatment of OI. In this study, SrR therapy was investigated to assess its effects on fracture frequency and bone mass and strength in an animal model of OI, the oim/oim mouse. Three-week-old oim/oim and wt/wt mice were treated with either SrR or vehicle (Veh) for 11 weeks. After treatment, the average number of fractures sustained by SrR-treated oim/oim mice was significantly reduced compared to Veh-treated oim/oim mice. Micro-computed tomographic (μCT) analyses of femurs showed that both trabecular and cortical bone mass were significantly improved with SrR treatment in both genotypes. SrR significantly inhibited bone resorption, whereas bone formation indices were maintained. Biomechanical testing revealed improved bone structural properties in both oim/oim and wild-type (wt/wt) mice under the treatment, whereas no significant effects on bone brittleness and material quality were observed. In conclusion, SrR was able to effectively reduce fractures in oim/oim mice by improving bone mass and strength and thus represents a potential therapy for the treatment of pediatric OI. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.

  13. Multidisciplinary Treatment of Severe Osteogenesis Imperfecta: Functional Outcomes at Skeletal Maturity.

    Science.gov (United States)

    Montpetit, Kathleen; Palomo, Telma; Glorieux, Francis H; Fassier, François; Rauch, Frank

    2015-10-01

    To determine the functional outcomes associated with long-term multidisciplinary treatment, intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation in children with severe osteogenesis imperfecta (OI) (diagnosed clinically as OI types III or IV). Retrospective study where outcomes were measured prospectively. Pediatric orthopedic hospital. Adolescents (N=41; age range, 15-21y) with severe OI (OI type III: n=17; OI type IV: n=24) who had started therapy before the age of 6 years, had received treatment for at least 10 years, and had achieved final height. Intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation. Pediatric Evaluation of Disability Inventory. At the time of the last available follow-up examination, none of the individuals diagnosed with OI type III (most severely affected group) was able to ambulate without ambulation aids, whereas 20 (83%) patients with OI type IV were able to ambulate without ambulation aids. Regarding self-care, we specifically assessed 8 skills that we deemed essential for living independently (grooming; dressing; toileting; bed, chair, toilet, tub, and car transfers). Only 6 (35%) of the youths with OI type III were able to complete all 8 items, whereas 23 (96%) individuals with OI type IV managed to perform all tasks. Teens with OI type III often needed assistance for the transfer to toilet, tub, and car and for personal hygiene and clothing management associated with toileting, usually because of limitations in upper-extremity function. These observations suggest that further improvements in the functional status of the most severely affected children with OI are contingent on advances in the clinical management of upper-extremity issues. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  14. Evidence for a Role for Nanoporosity and Pyridinoline Content in Human Mild Osteogenesis Imperfecta.

    Science.gov (United States)

    Paschalis, Eleftherios P; Gamsjaeger, Sonja; Fratzl-Zelman, Nadja; Roschger, Paul; Masic, Admir; Brozek, Wolfgang; Hassler, Norbert; Glorieux, Francis H; Rauch, Frank; Klaushofer, Klaus; Fratzl, Peter

    2016-05-01

    Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous connective tissue disorder characterized by bone fragility that arises from decreased bone mass and abnormalities in bone material quality. OI type I represents the milder form of the disease and according to the original Sillence classification is characterized by minimal skeletal deformities and near-normal stature. Raman microspectroscopy is a vibrational spectroscopic technique that allows the determination of bone material properties in bone biopsy blocks with a spatial resolution of ∼1 µm, as a function of tissue age. In the present study, we used Raman microspectroscopy to evaluate bone material quality in transiliac bone biopsies from children with a mild form of OI, either attributable to collagen haploinsufficiency OI type I (OI-Quant; n = 11) or aberrant collagen structure (OI-Qual; n = 5), as a function of tissue age, and compared it against the previously published values established in a cohort of biopsies from healthy children (n = 54, ages 1 to 23 years). The results indicated significant differences in bone material compositional characteristics between OI-Quant patients and healthy controls, whereas fewer were evident in the OI-Qual patients. Differences in both subgroups of OI compared with healthy children were evident for nanoporosity, mineral maturity/crystallinity as determined by maxima of the v1 PO4 Raman band, and pyridinoline (albeit in different direction) content. These alterations in bone material compositional properties most likely contribute to the bone fragility characterizing this disease. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  15. Effect of sclerostin antibody treatment in a mouse model of severe osteogenesis imperfecta.

    Science.gov (United States)

    Roschger, Andreas; Roschger, Paul; Keplingter, Petra; Klaushofer, Klaus; Abdullah, Sami; Kneissel, Michaela; Rauch, Frank

    2014-09-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I production in osteoblasts. Stimulation of bone formation through sclerostin antibody treatment (Sost-ab) has shown promising results in mouse models of relatively mild OI. We assessed the effect of once-weekly intravenous Sost-ab injections for 4weeks in male Col1a1(Jrt)/+mice, a model of severe dominant OI, starting either at 4weeks (growing mice) or at 20weeks (adult mice) of age. Sost-ab had no effect on weight or femur length. In OI mice, no significant treatment-associated differences in serum markers of bone formation (alkaline phosphatase activity, procollagen type I N-propeptide) or resorption (C-telopeptide of collagen type I) were found. Micro-CT analyses at the femur showed that Sost-ab treatment was associated with higher trabecular bone volume and higher cortical thickness in wild type mice at both ages and in growing OI mice, but not in adult OI mice. Three-point bending tests of the femur showed that in wild type but not in OI mice, Sost-ab was associated with higher ultimate load and work to failure. Quantitative backscattered electron imaging of the femur did not show any effect of Sost-ab on CaPeak (the most frequently occurring calcium concentration in the bone mineral density distribution), regardless of genotype, age or measurement location. Thus, Sost-ab had a larger effect in wild type than in Col1a1(Jrt)/+mice. Previous studies had found marked improvements of Sost-ab on bone mass and strength in an OI mouse model with a milder phenotype. Our data therefore suggest that Sost-ab is less effective in a more severely affected OI mouse model. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Sclerostin Antibody Treatment Improves the Bone Phenotype of Crtap(-/-) Mice, a Model of Recessive Osteogenesis Imperfecta.

    Science.gov (United States)

    Grafe, Ingo; Alexander, Stefanie; Yang, Tao; Lietman, Caressa; Homan, Erica P; Munivez, Elda; Chen, Yuqing; Jiang, Ming Ming; Bertin, Terry; Dawson, Brian; Asuncion, Franklin; Ke, Hua Zhu; Ominsky, Michael S; Lee, Brendan

    2016-05-01

    Osteogenesis imperfecta (OI) is characterized by low bone mass, poor bone quality, and fractures. Standard treatment for OI patients is limited to bisphosphonates, which only incompletely correct the bone phenotype, and seem to be less effective in adults. Sclerostin-neutralizing antibodies (Scl-Ab) have been shown to be beneficial in animal models of osteoporosis, and dominant OI resulting from mutations in the genes encoding type I collagen. However, Scl-Ab treatment has not been studied in models of recessive OI. Cartilage-associated protein (CRTAP) is involved in posttranslational type I collagen modification, and its loss of function results in recessive OI. In this study, we treated 1-week-old and 6-week-old Crtap(-/-) mice with Scl-Ab for 6 weeks (25 mg/kg, s.c., twice per week), to determine the effects on the bone phenotype in models of "pediatric" and "young adult" recessive OI. Vehicle-treated Crtap(-/-) and wild-type (WT) mice served as controls. Compared with control Crtap(-/-) mice, micro-computed tomography (μCT) analyses showed significant increases in bone volume and improved trabecular microarchitecture in Scl-Ab-treated Crtap(-/-) mice in both age cohorts, in both vertebrae and femurs. Additionally, Scl-Ab improved femoral cortical parameters in both age cohorts. Biomechanical testing showed that Scl-Ab improved parameters of whole-bone strength in Crtap(-/-) mice, with more robust effects in the week 6 to 12 cohort, but did not affect the increased bone brittleness. Additionally, Scl-Ab normalized the increased osteoclast numbers, stimulated bone formation rate (week 6 to 12 cohort only), but did not affect osteocyte density. Overall, our findings suggest that Scl-Ab treatment may be beneficial in the treatment of recessive OI caused by defects in collagen posttranslational modification. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.

  17. Tracing the pathway between mutation and phenotype in osteogenesis imperfecta: Isolation of mineralization-specific genes

    Energy Technology Data Exchange (ETDEWEB)

    Culbert, A.A.; Wallis, G.A.; Kadler, K.E. [Univ. of Manchester (United Kingdom)

    1996-05-03

    The brittleness of bone in people with lethal (type II) osteogenesis imperfecta, a heritable disorder caused by mutations in the type I collagen genes, arises from the deposition of abnormal collagen in the bone matrix. The inability of the abnormal collagen to participate in mineralization may be caused by its failure to interact with other bone proteins. Here, we have designed a strategy to isolate the genes important for mineralization of collagen during bone formation. Cells isolated from 16-day embryonic chick calvaria and seeded post-confluence in culture deposited a mineralized matrix over a period of 2 weeks. Chick skin fibroblasts seeded and cultured under the same conditions did not mineralize. Using RT-PCR, we prepared short cDNAs ({approximately}300 bp) corresponding to the 3{prime} ends of mRNA from fibroblasts and separately from the mineralizing calvarial cells. Subtractive cDNA hybridization generated a pool of cDNAs that were specific to mineralizing calvarial cells but not to fibroblasts. Screening of 100,000 plaques of a chick bone ZAP Express cDNA library with this pool of mineralizing-specific cDNAs identified ten clones which comprised full-length cDNAs for the bone proteins osteopontin (eight of the ten positives), bone sialoprotein II (one of the ten positives), and cystatin (one of the ten positives). cDNAs for type I collagen, fibronectin, alkaline phosphatase, house-keeping genes, and other genes expressed in fibroblasts were not identified in this preliminary screen. The pool of short cDNAs is likely to comprise cDNAs for further bone-specific genes and will be used to screen the entire bone cDNA library of 4.2 million clones. 30 refs., 4 figs.

  18. Echocardiographic Evidence of Early Diastolic Dysfunction in Asymptomatic Children with Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Khalfan S. Al-Senaidi

    2015-11-01

    Full Text Available Objectives: Structural and functional cardiovascular abnormalities have been reported in adults with osteogenesis imperfecta (OI; however, there is a lack of paediatric literature on this topic. This study aimed to investigate cardiovascular abnormalities in children with OI in comparison to a control group. Methods: This case-control study was conducted at the Sultan Qaboos University Hospital in Muscat, Oman, between May 2013 and August 2014. Data from eight patients with OI and 24 healthy controls were compared using conventional and tissue Doppler echocardiography (TDE. Results: The OI group had significantly lower peak early mitral valve flow velocity (P = 0.027, peak a-wave reversal in the pulmonary vein (P = 0.030 and peak early diastolic velocity of the mitral valve and upper septum (P = 0.001 each. The peak late diastolic velocities of the mitral valve (P = 0.002 and the upper septum (P = 0.037 were significantly higher in the OI group; however, the peak early/late diastolic velocity ratios of the mitral valve (P = 0.002 and upper septum (P = 0.001 were significantly lower. Left ventricular dimensions and aortic and pulmonary artery diameters were larger in the OI group when indexed for body surface area. Both groups had normal systolic cardiac function. Conclusion: Children with OI had normal systolic cardiac function. However, changes in myocardial tissue Doppler velocities were suggestive of early diastolic cardiac dysfunction. They also had increased left ventricular dimensions and greater vessel diameters. These findings indicate the need for early and detailed structural and functional echocardiographic assessment and follow-up of young patients with OI.

  19. Local transplantation is an effective method for cell delivery in the osteogenesis imperfecta murine model.

    Science.gov (United States)

    Pauley, Penelope; Matthews, Brya G; Wang, Liping; Dyment, Nathaniel A; Matic, Igor; Rowe, David W; Kalajzic, Ivo

    2014-09-01

    Osteogenesis imperfecta is a serious genetic disorder that results from improper type I collagen production. We aimed to evaluate whether bone marrow stromal cells (BMSC) delivered locally into femurs were able to engraft, differentiate into osteoblasts, and contribute to formation of normal bone matrix in the osteogenesis imperfect murine (oim) model. Donor BMSCs from bone-specific reporter mice (Col2.3GFP) were expanded in vitro and transplanted into the femoral intramedullary cavity of oim mice. Engraftment was evaluated after four weeks. We detected differentiation of donor BMSCs into Col2.3GFP+ osteoblasts and osteocytes in cortical and trabecular bone of transplanted oim femurs. New bone formation was detected by deposition of dynamic label in the proximity to the Col2.3GFP+ osteoblasts, and new bone showed more organized collagen structure and expression of type I α2 collagen. Col2.3GFP cells were not found in the contralateral femur indicating that transplanted osteogenic cells did not disseminate by circulation. No osteogenic engraftment was observed following intravenous transplantation of BMSCs. BMSC cultures derived from transplanted femurs showed numerous Col2.3GFP+ colonies, indicating the presence of donor progenitor cells. Secondary transplantation of cells recovered from recipient femurs and expanded in vitro also showed Col2.3GFP+ osteoblasts and osteocytes confirming the persistence of donor stem/progenitor cells. We show that BMSCs delivered locally in oim femurs are able to engraft, differentiate into osteoblasts and osteocytes and maintain their progenitor potential in vivo. This suggests that local delivery is a promising approach for introduction of autologous MSC in which mutations have been corrected.

  20. Intrafibrillar Mineral May be Absent in Dentinogenesis Imperfecta Type II (DI-II)

    Energy Technology Data Exchange (ETDEWEB)

    Pople, John A

    2001-03-29

    High-resolution synchrotron radiation computed tomography (SRCT) and small angle x-ray scattering (SAXS) were performed on normal and dentinogenesis imperfecta type II (DI-II) teeth. Three normal and three DI-II human third molars were used in this study. The normal molars were unerupted and had intact enamel; donors were female and ranged in age from 18-21y. The DI-II specimens, which were also unerupted with intact enamel, came from a single female donor age 20y. SRCT showed that the mineral concentration was 33% lower on average in the DI-II dentin with respect to normal dentin. The SAXS spectra from normal dentin exhibited low-angle diffraction peaks at harmonics of 67.6 nm, consistent with nucleation and growth of the apatite phase within gaps in the collagen fibrils (intrafibrillar mineralization). In contrast, the low-angle peaks were almost nonexistent in the DI-II dentin. Crystallite thickness was independent of location in both DI-II and normal dentin, although the crystallites were significantly thicker in DI-II dentin (6.8 nm (s.d. = 0.5) vs 5.1 nm (s.d. = 0.6)). The shape factor of the crystallites, as determined by SAXS, showed a continuous progression in normal dentin from roughly one-dimensional (needle-like) near the pulp to two-dimensional (plate-like) near the dentin-enamel junction. The crystallites in DI-II dentin, on the other hand, remained needle-like throughout. The above observations are consistent with an absence of intrafibrillar mineral in DI-II dentin.

  1. Diaphyseal Femur Fractures in Osteogenesis Imperfecta: Characteristics and Relationship With Bisphosphonate Treatment.

    Science.gov (United States)

    Trejo, Pamela; Fassier, François; Glorieux, Francis H; Rauch, Frank

    2017-05-01

    Several recent case reports have suggested that bisphosphonate treatment in individuals with osteogenesis imperfecta (OI) is causally related to atypical femur fractures. However, it is not known whether atypical femur fractures are actually more frequent in patients who have received bisphosphonates. In the present study, we retrospectively analyzed 166 femur fractures in 119 children with a diagnosis of OI that had not undergone intramedullary rodding procedures. A total of 130 fractures in 90 patients occurred in femurs with preexisting deformities (age at fracture between 1 month and 19.9 years; 43 girls). Because deformities are a typical cause of fracture in OI, deformed femurs were excluded from the analysis of atypical fractures. However, it was noted that in deformed femurs a transverse fracture pattern (one of the criteria of atypical fractures) was associated with a moderate to severe OI phenotype and not related to bisphosphonate treatment. Of the 36 fractures that occurred in nondeformed femurs (30 individuals; age at fracture between 1 month and 17.4 years; 13 girls), 11 (in nine children) occurred during bisphosphonate treatment. Three of these fractures (27%) resembled atypical femur fractures. Among the 25 femur fractures (23 patients) that occurred in the absence of prior bisphosphonate treatment, 8 (22%) resembled atypical femur fractures. Logistic regression analysis showed that bisphosphonate treatment history was not associated with the occurrence of atypical fractures. In contrast, the presence of moderate to severe OI (defined as any OI type other than OI type I) was strongly associated with atypical femur fractures. Thus, we observed an atypical appearance in about a quarter of nondeformed femur fractures that occurred in children with OI. Such atypical femur fractures seemed to be related to the severity of OI rather than to bisphosphonate treatment history. © 2016 American Society for Bone and Mineral Research. © 2016 American Society

  2. Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates.

    Science.gov (United States)

    Arponen, Heidi; Vuorimies, Ilkka; Haukka, Jari; Valta, Helena; Waltimo-Sirén, Janna; Mäkitie, Outi

    2015-03-01

    Cranial base pathology is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze whether bisphosphonate treatment, used to improve bone strength, could also prevent the development of craniocervical junction pathology (basilar impression, basilar invagination, or platybasia) in children with OI. In this single-center retrospective study the authors analyzed the skull base morphology from lateral skull radiographs and midsagittal MR images (total of 94 images), obtained between the ages of 0 and 25 years in 39 bisphosphonate-treated OI patients. The results were compared with age-matched normative values and with findings in 70 OI patients who were not treated with bisphosphonates. In addition to cross-sectional data, longitudinal data were available from 22 patients with an average follow-up period of 7.6 years. The patients, who had OI types I, III, IV, VI, and VII, had been treated with zoledronic acid, pamidronate, or risedronate for 3.2 years on average. Altogether 33% of the 39 bisphosphonate-treated patients had at least 1 cranial base anomaly, platybasia being the most prevalent diagnosis (28%). Logistic regression analysis suggested a higher risk of basilar impression or invagination in patients with severe OI (OR 22.04) and/or older age at initiation of bisphosphonate treatment (OR 1.45), whereas a decreased risk was associated with longer duration of treatment (OR 0.28). No significant associations between age, height, or cumulative bisphosphonate dose and the risk for cranial base anomaly were detected. In longitudinal evaluation, Kaplan-Meier curves suggested delayed development of cranial base pathology in patients treated with bisphosphonates but the differences from the untreated group were not statistically significant. These findings indicate that cranial base pathology may develop despite bisphosphonate treatment. Early initiation of bisphosphonate treatment may delay development of craniocervical junction pathology

  3. Study of the Determinants of Vitamin D Status in Pediatric Patients With Osteogenesis Imperfecta.

    Science.gov (United States)

    Zambrano, Marina B; Brizola, Evelise; Pinheiro, Bruna; Vanz, Ana Paula; Mello, Elza D; Félix, Têmis Maria

    2016-01-01

    Vitamin D is essential to the development and maintenance of the skeleton, especially for children with bone disorders such as osteogenesis imperfecta (OI). We evaluated serum 25-hydroxyvitamin D (25-OHD) levels to assess the relationship between determinants of vitamin D status in pediatric patients with OI. This cross-sectional study evaluated sex, age, weight, height, body mass index, OI type, sunscreen use, season of assessment, sun exposure, vitamin D and calcium supplementation, bisphosphonate treatment, bone mineral density (BMD), milk and soda consumption, mobility, and time of sedentary activity. Levels of serum 25-OHD, calcium, parathyroid hormone (PTH), phosphorus, and alkaline phosphatase (ALP) were analyzed. Serum levels of 25-OHD were classified according to sufficient (>30 ng/ml or 75 nmol/L), insufficient (20-30 ng/ml or 50-75 nmol/L), moderately deficient (20-10 ng/ml or 50-25 nmol/L), and severely deficient (<10 ng/ml or 25 nmol/L). Fifty-two patients were included and 46 (88.4%) were classified as having insufficient or deficient 25-OHD. An inverse correlation between serum 25-OHD and time of sedentary activity (r = -0.597, p < 0.001) and a positive correlation with height (r = 0.521, p = 0.046) and whole body BMD (r = 0.586, p = 0.022) were observed. A significant difference between the number of glasses of milk consumed (p = 0.010) was observed. To optimize bone health, patients with OI need to be educated regarding habits that can improve serum 25-OHD levels, such as a reduction in periods of inactivity, the importance of sun exposure, and increasing consumption of milk and fortified dairy products.

  4. Skeletal dysplasia in perinatal lethal osteogenesis imperfecta. A complex disorder of endochondral and intramembranous ossification.

    Science.gov (United States)

    Marion, M J; Gannon, F H; Fallon, M D; Mennuti, M T; Lodato, R F; Kaplan, F S

    1993-08-01

    Osteogenesis imperfecta (OI) Type II is a rare heritable disorder of bone matrix that results in catastrophic congenital skeletal dysplasia. Two cases of OI Type II had symmetric rhizomelic skeletal dysplasia apparent on ultrasound at 16 and 20 weeks' gestation. Histologic and histochemical studies performed on skeletal tissue from fetal autopsies showed the following: (1) abnormal growth plate tissue characterized by failure of formation of primary bony spongiosa; (2) persistence of calcified cartilage bars in the diaphysis; (3) metaphyseal microfractures; (4) abundant cartilaginous fracture callus; (5) absence of bony callus; (6) failure of formation of intramembranous cortical diaphyseal bone; (7) angulation of long bones in portions of the metadiaphyses bordered by fracture callus; and (8) mechanical failure of the perichondral ring of LaCroix with a normal fibrous ossification groove of Ranvier. These findings suggest that skeletal dysplasia in OI Type II results from the action of muscular forces on a skeleton weakened by a complex disorder of endochondral and intramembranous ossification. The paucity of primary metaphyseal trabeculae and subperiosteal cortical bone leads to pathologic fractures of the immature fiber bone and an imperfect attempt at fracture repair. Angulation and shortening of long bones occurs between numerous sites of focal endochondral fracture callus. Mechanical failure of the fibrous perichondral ring leads to further collapse and shortening without obvious functional impairment of the fibrous ossification groove. Perinatal lethal OI provides insight into how a molecular disorder predominantly of Type I collagen metabolism results in pathology of numerous tissues, leading to severe skeletal dysplasia without primarily affecting chondrogenesis.

  5. Safety and efficacy of denosumab in children with osteogenesis imperfect--a first prospective trial.

    Science.gov (United States)

    Hoyer-Kuhn, H; Franklin, J; Allo, G; Kron, M; Netzer, C; Eysel, P; Hero, B; Schoenau, E; Semler, O

    2016-03-01

    Osteogenesis imperfecta (OI) is a rare hereditary disease leading to bone fragility. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. Aim of this study was a 48-week, open-label, pilot study of the safety and efficacy of denosumab in 10 children with OI. Ten patients (age range: 5.0-11.0 years; at least two years of prior bisphosphonate treatment) with genetically confirmed OI were studied. Denosumab was administered subcutaneously every 12 weeks with 1 mg/kg body weight. Primary endpoint was change of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 48 weeks. Safety was assessed by bone metabolism markers and adverse event reporting. Mean relative change of lumbar aBMD was +19 % (95%-CI: 7-31%). Lumbar spine aBMD Z-Scores increased from -2.23±2.03 (mean±SD) to -1.27±2.37 (p=0.0006). Mobility did not change (GMFM-88 +2.72±4.62% (p=0.16); one-minute walking test +11.00±15.82 m (p=0.15). No severe side effects occurred. On average, there was a significant increase in lumbar spine aBMD percent change after 48 weeks of denosumab. There was no change in mobility parameters and no serious adverse events. Further trials are necessary to assess long-term side effects and efficacy.

  6. Unique micro- and nano-scale mineralization pattern of human osteogenesis imperfecta type VI bone.

    Science.gov (United States)

    Fratzl-Zelman, Nadja; Schmidt, Ingo; Roschger, Paul; Roschger, Andreas; Glorieux, Francis H; Klaushofer, Klaus; Wagermaier, Wolfgang; Rauch, Frank; Fratzl, Peter

    2015-04-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of inheritable connective tissue disorders characterized by mutation in genes involved in collagen synthesis and leading to increased bone fragility, low bone mass, impaired bone material properties and abnormally high bone matrix mineralization. Recessive OI type VI is caused by mutation in SERPINF1 leading to a loss-of-function of pigment epithelium-derived factor (PEDF) a collagen-binding protein with potent antiangiogenic activity. Affected patients develop a severe OI phenotype with a striking histological characteristic, rare in other OI types, of an excess of osteoid tissue and prolonged mineralization lag time. To get insights into matrix mineralization, we evaluated biopsies from 9 affected children by quantitative and by high-resolution backscattered electron imaging and assessed bone mineralization density distribution. Thickness, shape and arrangement of mineral particles were measured in a subset of 4 patients by synchrotron small angle X-ray scattering. Typical calcium content in the bone matrix was found to be increased compared to controls, even exceeding values found previously in OI patients with collagen-gene mutations. A main characteristic however, is the coexistence of this highly mineralized bone matrix with seams showing abnormally low mineral content. Atypical collagen fibril organization was found in the perilacunar region of young osteocytes, suggesting a disturbance in the early steps of mineralization. These observations are consistent with the presence of a heterogeneous population of mineral particles with unusual size, shape and arrangement, especially in the region with lower mineral content. The majority of the particles in the highly mineralized bone areas were less disorganized, but smaller and more densely packed than in controls and in previously measured OI patients. These data suggest that the lack of PEDF impairs a proper osteoblast-osteocyte transition and consequently

  7. Zoledronic acid in children with osteogenesis imperfecta and Bruck syndrome: a 2-year prospective observational study.

    Science.gov (United States)

    Otaify, G A; Aglan, M S; Ibrahim, M M; Elnashar, M; El Banna, R A S; Temtamy, S A

    2016-01-01

    Treatment with zoledronic acid (ZA) over 2 years, among 33 children with osteogenesis imperfecta (OI) and five Bruck syndrome cases, showed reduction in fracture rates, pain, and improvement in bone mineral density (BMD) and motor milestones of development. This is the first study reporting the use of bisphosphonates in patients with Bruck syndrome (BS). OI and BS are genetic disorders that result in bone fragility and reduced BMD. There is little literature describing the efficacy and safety of ZA in this population. In this study, we assess the response to treatment with ZA at six monthly intervals in Egyptian children with OI and BS for a period of 2 years. Thirty-three patients with OI and five patients with BS were treated with 0.1 mg/kg ZA intravenously every 6 months for 2 years during which they were followed up using different parameters. A clinical severity score (CSS) was applied to the patients before and 2 years after the start of therapy. Comparison of disease severity and response to ZA treatment between autosomal-dominant (AD) and autosomal-recessive (AR) OI patients was also done. After 6 months of treatment, OI and BS patients showed a significant increase in BMD Z-scores (P < 0.003 in the spine and P < 0.004 in the hip), together with a significant drop in fracture rate (P < 0.001), relief of pain (P < 0.001), and improvement in ambulation (P < 0.001). CSS was significantly reduced after 2 years of treatment in both OI and BS patients. AR-OI patients were more severely affected than AD-OI patients and showed more significant improvement. Zoledronic acid proved to be safe and effective in the treatment of OI and BS. The biannual infusion protocol was convenient to patients. There was a positive correlation between disease severity and benefits of the treatment. The use of the CSS proved to be of value in the assessment of the degree of severity in OI, and with some modifications, it was a valuable tool for the assessment of

  8. Ultrastructural and histological findings on examination of skin in osteogenesis imperfecta: a novel study.

    Science.gov (United States)

    Balasubramanian, Meena; Wagner, Bart E; Peres, Luiz C; Sobey, Glenda J; Parker, Michael J; Dalton, Ann; Arundel, Paul; Bishop, Nicholas J

    2015-04-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity for fractures. It is a variable condition with a range of clinical severities. The histological and ultrastructural findings in the skin of patients with OI have not been described in detail in the previously published literature. Although protein analysis of cultured fibroblasts has historically been used in the diagnostic work-up of OI patients, other aspects of skin examination are not routinely performed as part of the diagnostic pathway in patients with OI. The aims of this study were to perform histological and ultrastructural examination of skin biopsies in patients with OI. This was to identify common and distinguishing features in the numerous genetically distinct subtypes of OI and compare the findings with those in patients who did not present with fractures, and to enable the use of the results thus obtained to aid in the diagnostic work-up of patients with OI. As part of a larger research study set-up to identify clinical features and natural history in patients with atypical features of OI, skin biopsy and examination (histology and electron microscopy) were undertaken. Genetic analysis and ancillary investigations were also performed to identify similarities within this group and to differentiate this group from the 'normal' population. At the end of this study, we were able to demonstrate that the histological and electron microscopic findings on a skin biopsy may be an indicator of the likelihood of identifying a pathogenic mutation in type 1 collagen genes. This is because patients with specific findings on examination, such as elastic fibre area fraction (on histological analysis), collagen fibril diameter variability, deviation from the expected mean and collagen flowers (on electron microscopy), are more likely to be positive on genetic analyses. This has, in turn, provided more insight into the

  9. The incidence of spondylolysis and spondylolisthesis in children with osteogenesis imperfecta.

    Science.gov (United States)

    Hatz, Daniel; Esposito, Paul W; Schroeder, Bruce; Burke, Bridget; Lutz, Richard; Hasley, Brian P

    2011-09-01

    Spondylolysis and spondylolisthesis are common abnormalities of the lumbar spine. The incidence of these diagnoses is recognized in the healthy population. However, their incidence in osteogenesis imperfecta (OI) patients is less well defined. This is a retrospective radiographic review of patients treated in the OI clinic from a single institution. Lateral radiographs were reviewed on all available patients to assess the incidence of spondylolysis and spondylolisthesis in this patient population. The morphology of the pedicle and pars interarticularis was also evaluated to identify any abnormalities or dysplasia of these structures. One hundred ten of the 139 patients treated in the OI clinic met the inclusion criteria for this study. Of these patients, 79% (87 of 110) were ambulatory. The overall incidence of spondylolysis in this pediatric OI population was found to be 8.2% (9 of 110) at an average age of 7.5 years. The incidence of spondylolisthesis was 10.9% (12 of 110) at an average age of 6.5 years with 75% (3 of 12) being isthmic type and 25% (3 of 12) dysplastic. The combined incidence of spondylolysis and spondylolisthesis was 19.2%. Incidentally, the pedicle length was noted to be elongated in 40.0% (44 of 110) of this OI population. This study found that the incidence of spondylolysis in a group of children with OI was much higher than in the normal pediatric population, which has been reported to be 2.6% to 4.0%. This incidence was also found to be higher than previously reported incidence of spondylolysis in OI patients (5.3%). The incidence of spondylolisthesis was also found to be much higher than that of the normal pediatric population (4.2%). It is important to recognize this higher incidence of these abnormalities and to anticipate future associated symptoms and potential worsening listhesis that can clinically affect the lifestyles of these children and potentially require surgical treatment. The clinical significance of these findings will

  10. Anesthetic management for combined mitral valve replacement and aortic valve repair in a patient with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Huang Jiapeng

    2011-01-01

    Full Text Available Osteogenesis imperfecta is a rare disorder of connective tissues and presents multiple challenges, including difficult airway, hyperthermia, coagulopathy and respiratory dysfunction, for anesthesiologists, especially during cardiac surgery. We present anesthetic management of a patient with osteogenesis impertecta during double valve surgery. Dexmedetomidine infusion minimized the risks of malignant hyperthermia. Glidescope and in-line stabilization facilitated endotracheal intubation and protected his oral structures and cervical spine. Transesophageal echocardiography (TEE diagnosed a flail A3 segment and redundant left coronary cusp causing mitral and aortic regurgitation. The mitral valve was replaced and the aortic valve repaired. Coagulopathy was corrected according to comprehensive coagulation analysis. Glidescope, dexmedetomidine, coagulation analysis and TEE could facilitate anesthetic management in these patients.

  11. Hyperplastic callus formation in osteogenesis imperfecta type V: follow-up of three generations over ten years

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    Cheung, Moira S.; Azouz, E.M.; Glorieux, Francis H. [Shriners Hospital for Children and McGill University, Genetics Unit, Montreal, Quebec (Canada); Rauch, Frank [Shriners Hospital for Children and McGill University, Genetics Unit, Montreal, Quebec (Canada); Shriners Hospital for Children, Genetics Unit, Montreal, Quebec (Canada)

    2008-05-15

    Hyperplastic callus (HPC) formation is a prominent feature of osteogenesis imperfecta (OI) type V; however, little is known about its long-term outcome. In this case report we describe the occurrence, appearance and course of a femoral HPC in a patient with OI type V during 10 years of follow-up. Radiographs of HPC in this child were compared and contrasted with HPC formation in the femur of his father and paternal grandfather, who also were affected with OI type V. This case report makes it clear that HPC can lead to significant morbidity, not only in the acute phase but also long term as a result of residual alteration in bone architecture. (orig.)

  12. Hyperplastic callus formation in osteogenesis imperfecta type V: follow-up of three generations over ten years

    International Nuclear Information System (INIS)

    Cheung, Moira S.; Azouz, E.M.; Glorieux, Francis H.; Rauch, Frank

    2008-01-01

    Hyperplastic callus (HPC) formation is a prominent feature of osteogenesis imperfecta (OI) type V; however, little is known about its long-term outcome. In this case report we describe the occurrence, appearance and course of a femoral HPC in a patient with OI type V during 10 years of follow-up. Radiographs of HPC in this child were compared and contrasted with HPC formation in the femur of his father and paternal grandfather, who also were affected with OI type V. This case report makes it clear that HPC can lead to significant morbidity, not only in the acute phase but also long term as a result of residual alteration in bone architecture. (orig.)

  13. Microstructure and compressive mechanical properties of cortical bone in children with osteogenesis imperfecta treated with bisphosphonates compared with healthy children.

    Science.gov (United States)

    Imbert, Laurianne; Aurégan, Jean-Charles; Pernelle, Kélig; Hoc, Thierry

    2015-06-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by a change in bone tissue quality, but little data are available to describe the factors involved at the macroscopic scale. To better understand the effect of microstructure alterations on the mechanical properties at the sample scale, we studied the structural and mechanical properties of six cortical bone samples from children with OI treated with bisphosphonates and compared them to the properties of three controls. Scanning electron microscopy, high resolution computed tomography and compression testing were used to assess these properties. More resorption cavities and a higher osteocyte lacunar density were observed in OI bone compared with controls. Moreover, a higher porosity was measured for OI bones along with lower macroscopic Young's modulus, yield stress and ultimate stress. The microstructure was impaired in OI bones; the higher porosity and osteocyte lacunar density negatively impacted the mechanical properties and made the bone more prone to fracture. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. A novel splicing mutation in COL1A1 gene caused type I osteogenesis imperfecta in a Chinese family.

    Science.gov (United States)

    Peng, Hao; Zhang, Yuhui; Long, Zhigao; Zhao, Ding; Guo, Zhenxin; Xue, Jinjie; Xie, Zhiguo; Xiong, Zhimin; Xu, Xiaojuan; Su, Wei; Wang, Bing; Xia, Kun; Hu, Zhengmao

    2012-07-10

    Osteogenesis imperfect (OI) is a heritable connective tissue disorder with bone fragility as a cardinal manifestation, accompanied by short stature, dentinogenesis imperfecta, hyperlaxity of ligaments and skin, blue sclerae and hearing loss. Dominant form of OI is caused by mutations in the type I procollagen genes, COL1A1/A2. Here we identified a novel splicing mutation c.3207+1G>A (GenBank ID: JQ236861) in the COL1A1 gene that caused type I OI in a Chinese family. RNA splicing analysis proved that this mutation created a new splicing site at c.3200, and then led to frameshift. This result further enriched the mutation spectrum of type I procollagen genes. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength.

    Science.gov (United States)

    Sinder, B P; White, L E; Salemi, J D; Ominsky, M S; Caird, M S; Marini, J C; Kozloff, K M

    2014-08-01

    Treatments to reduce fracture rates in adults with osteogenesis imperfecta are limited. Sclerostin antibody, developed for treating osteoporosis, has not been explored in adults with OI. This study demonstrates that treatment of adult OI mice respond favorably to sclerostin antibody therapy despite retention of the OI-causing defect. Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk. Although OI fracture risk is greatest before puberty, adults with OI remain at risk of fracture. Antiresorptive bisphosphonates are commonly used to treat adult OI, but have shown mixed efficacy. New treatments which consistently improve bone mass throughout the skeleton may improve patient outcomes. Neutralizing antibodies to sclerostin (Scl-Ab) are a novel anabolic therapy that have shown efficacy in preclinical studies by stimulating bone formation via the canonical wnt signaling pathway. The purpose of this study was to evaluate Scl-Ab in an adult 6 month old Brtl/+ model of OI that harbors a typical heterozygous OI-causing Gly > Cys substitution on Col1a1. Six-month-old WT and Brtl/+ mice were treated with Scl-Ab (25 mg/kg, 2×/week) or Veh for 5 weeks. OCN and TRACP5b serum assays, dynamic histomorphometry, microCT and mechanical testing were performed. Adult Brtl/+ mice demonstrated a strong anabolic response to Scl-Ab with increased serum osteocalcin and bone formation rate. This anabolic response led to improved trabecular and cortical bone mass in the femur. Mechanical testing revealed Scl-Ab increased Brtl/+ femoral stiffness and strength. Scl-Ab was successfully anabolic in an adult Brtl/+ model of OI.

  16. Complete Remodeling After Conservative Treatment of a Severely Angulated Odontoid Fracture in a Patient With Osteogenesis Imperfecta: A Case Report.

    Science.gov (United States)

    Colo, Dino; Schlösser, Tom P C; Oostenbroek, Hubert J; Castelein, René M

    2015-09-15

    Case report. This is the first case report describing successful healing and remodeling of a traumatic odontoid fracture that was dislocated and severely angulated in a patient with osteogenesis imperfecta who was treated conservatively. Osteogenesis imperfecta (OI) is a rare genetic disorder resulting in a low bone mass and bone fragility, predisposing these patients to fractures that often occur at a young age. Although any bone in the body may be involved, odontoid fractures are uncommon in this population. Because of a very high fusion rate, conservative management is accepted as a safe and efficient treatment of fractures of the odontoid in children. Several authors, however, recommend surgical treatment of patients who have failure of conservative treatment and have severe angulation or displacement of the odontoid. A 5-year-old female, diagnosed with OI type I, presented with neck pain without any neurological deficits after falling out of a rocking chair backward, with her head landing first on the ground. Computed tomography confirmed a type III odontoid fracture without dislocation and she was initially treated with a rigid cervical orthosis. At 1 and 2 months of follow-up, progressive severe angulation of the odontoid was observed but conservative treatment was maintained as the space available for the spinal cord was sufficient and also considering the patient's history of OI. Eight months postinjury, she had no clinical symptoms and there was osseous healing of the fracture with remodeling of the odontoid to normal morphology. Even in patients with OI, severely angulated odontoid fractures might have the capacity for osseous healing and complete remodeling under conservative treatment. 5.

  17. Genotype-phenotype analysis of a rare type of osteogenesis imperfecta in four Chinese families with WNT1 mutations.

    Science.gov (United States)

    Liu, Yi; Song, Lijie; Ma, Doudou; Lv, Fang; Xu, Xiaojie; Wang, Jianyi; Xia, Weibo; Jiang, Yan; Wang, Ou; Song, Yuwen; Xing, Xiaoping; Asan; Li, Mei

    2016-10-01

    Osteogenesis imperfecta (OI) is a rare inherited disease characterized by increased bone fragility and vulnerability to fractures. Recently, WNT1 is identified as a new candidate gene for OI, here we detect pathogenic mutations in WNT1 and analyze the genotype-phenotype association in four Chinese families with OI. We designed a targeted next generation sequencing panel with known fourteen OI-related genes. We applied the approach to detect pathogenic mutations in OI patients and confirmed the mutations with Sanger sequencing and cosegregation analysis. Clinical fractures, bone mineral density (BMD) and the other clinical manifestations were evaluated. We also observed the effects of bisphosphonates in OI patients with WNT1 mutations. Four compound heterozygous mutations (c.110T>C; c.505 G>T; c. 385G>A; c.506 G>A) in WNT1 were detected in three unrelated families. These four mutations had not been reported yet. A recurrent homozygous mutation (c.506dupG) was identified in the other two families. These patients had moderate to severe OI, white to blue sclera, absence of dentinogenesis imperfecta and no brain malformation. We did not observe clear genotype-phenotype correlation in WNT1 mutated OI patients. Though bisphosphonates increased BMD in WNT1 related OI patients, height did not increase and fracture continued. We reported four novel heterozygous variants and confirmed a previous reported WNT1 mutation in four Chinese families with a clinical diagnosis of OI. Our study expanded OI spectrum and confirmed moderate to severe bone fragility induced by WNT1 defects. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Rib cage deformities alter respiratory muscle action and chest wall function in patients with severe osteogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Antonella LoMauro

    Full Text Available BACKGROUND: Osteogenesis imperfecta (OI is an inherited connective tissue disorder characterized by bone fragility, multiple fractures and significant chest wall deformities. Cardiopulmonary insufficiency is the leading cause of death in these patients. METHODS: Seven patients with severe OI type III, 15 with moderate OI type IV and 26 healthy subjects were studied. In addition to standard spirometry, rib cage geometry, breathing pattern and regional chest wall volume changes at rest in seated and supine position were assessed by opto-electronic plethysmography to investigate if structural modifications of the rib cage in OI have consequences on ventilatory pattern. One-way or two-way analysis of variance was performed to compare the results between the three groups and the two postures. RESULTS: Both OI type III and IV patients showed reduced FVC and FEV(1 compared to predicted values, on condition that updated reference equations are considered. In both positions, ventilation was lower in OI patients than control because of lower tidal volume (p<0.01. In contrast to OI type IV patients, whose chest wall geometry and function was normal, OI type III patients were characterized by reduced (p<0.01 angle at the sternum (pectus carinatum, paradoxical inspiratory inward motion of the pulmonary rib cage, significant thoraco-abdominal asynchronies and rib cage distortions in supine position (p<0.001. CONCLUSIONS: In conclusion, the restrictive respiratory pattern of Osteogenesis Imperfecta is closely related to the severity of the disease and to the sternal deformities. Pectus carinatum characterizes OI type III patients and alters respiratory muscles coordination, leading to chest wall and rib cage distortions and an inefficient ventilator pattern. OI type IV is characterized by lower alterations in the respiratory function. These findings suggest that functional assessment and treatment of OI should be differentiated in these two forms of the

  19. Osteogenesis imperfecta Type IV: a newly identified variant at position c.560 (G > T; p.Gly187Val) in the COL1A2 gene.

    Science.gov (United States)

    Usta, Akin; Karademir, Dilay; Sen, Eylem; Yazici, Selcuk; Adali, Ertan; Erdem, Erkan; Karacan, Meric

    2017-01-01

    Osteogenesis imperfecta is a clinically heterogenous disease caused by defective collagen syntesis associated with a mutation in the COL1A1 or COL1A2 genes. In this report, we present a case of osteogenesis imperfecta (OI) type IV, seen in a female fetus with incurved femurs at 18 weeks of gestation. Molecular analysis of the newborn revealed a novel mutation at position c.560 (c.560 G > T) of the exon 12 in the COL1A2 gene; which lead to the glycine modification with valine (p.Gly187Val) at codon 187. The pregnancy follow-up was uneventful. After delivery, the newborn underwent biphosponat therapy and no fracture was detected until 1 year old.

  20. Bone geometry, density and microarchitecture in the distal radius and tibia in adults with osteogenesis imperfecta type-1 assessed by HR-pQCT

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Hansen, Stinus

    2012-01-01

    Osteogenesis Imperfecta (OI) is a hereditary disorder characterized by decreased biosynthesis or impaired morphology of collagen type-1 that leads to decreased bone mass and increased bone fragility. We hypothesized that patients with OI have altered bone microstructure and bone geometry. In this......Osteogenesis Imperfecta (OI) is a hereditary disorder characterized by decreased biosynthesis or impaired morphology of collagen type-1 that leads to decreased bone mass and increased bone fragility. We hypothesized that patients with OI have altered bone microstructure and bone geometry...... treated with bisphosphonates. HR-pQCT at the distal radius and distal tibia and dual-energy X-ray absorptiomentry of total hip, femoral neck, trochanteric region and the lumbar spine (L1-L4) were performed. The patients were shorter than the controls (159¿±¿10¿cm vs. 170¿±¿9¿cm, p¿...

  1. Isolated olecranon fractures in children affected by osteogenesis imperfecta type I treated with single screw or tension band wiring system: Outcomes and pitfalls in relation to bone mineral density.

    Science.gov (United States)

    Persiani, Pietro; Ranaldi, Filippo M; Graci, Jole; De Cristo, Claudia; Zambrano, Anna; D'Eufemia, Patrizia; Martini, Lorena; Villani, Ciro

    2017-05-01

    The purpose of this study is to compare the results of 2 techniques, tension band wiring (TBW) and fixation with screws, in olecranon fractures in children affected with osteogenesis imperfecta (OI) type I. Between 2010 and 2014, 21 olecranon fractures in 18 children with OI (average age: 12 years old) were treated surgically. Ten patients were treated with the screw fixation and 11 with TBW. A total of 65% of olecranon fractures occurred as a result of a spontaneous avulsion of the olecranon during the contraction of the triceps muscle. The average follow-up was 36 months. Among the children treated with 1 screw, 5 patients needed a surgical revision with TBW due to a mobilization of the screw. In this group, the satisfactory results were 50%. In patients treated with TBW, the satisfactory results were 100% of the cases. The average Z-score, the last one recorded in the patients before the trauma, was -2.53 in patients treated with screw fixation and -2.04 in those treated with TBW. TBW represents the safest surgical treatment for patients suffering from OI type I, as it helps to prevent the rigidity of the elbow through an earlier recovery of the range of motion, and there was no loosening of the implant. In analyzing the average Z-score before any fracture, the fixation with screws has an increased risk of failure in combination with low bone mineral density.

  2. Osteogénesis imperfecta: mosaicismo germinal o evidencia de heterogeneidad genética. Presentación de una familia y revisión bibliográfica Osteogenesis imperfecta: germinal mosaicism or genetic heterogeneity evidence. Presentation of a family and a literature review

    Directory of Open Access Journals (Sweden)

    Iván Hernández García

    2007-09-01

    Full Text Available La osteogénesis imperfecta clasifica entre las displasias óseas por alteraciones en la densidad y los defectos del modelaje óseo. El tipo I es la forma más frecuente de la enfermedad y se caracteriza por un patrón de herencia autosómico dominante. No es infrecuente que la enfermedad aparezca producto de una nueva mutación. También se ha demostrado que puede ser producida por mosaicismos germinales. Este trabajo documenta, por primera vez en Cuba, el caso de una familia con 3 individuos de diferente sexo afectados por osteogénesis imperfecta de tipo I mientras ninguno de los progenitores lo está. Se discute la posibilidad etiológica de un mosaicismo germinal y se valora asimismo la posibilidad de un patrón de herencia distinto del dominante, lo cual aportaría nueva evidencia de heterogeneidad genética.Osteogenesis imperfecta is one of the bone dysplasias caused by altered density and bone model defects. Type I is the most common form of disease and is characterized by an autosomal dominant inheritance pattern. Sometimes, this disease occurs as a result of a new mutation. It has been also demonstrated that it can be caused by germ mosaicisms. This paper documented for the first time in Cuba the case of a family with three (3 individuals of both sexes affected by type-1 osteogenesis imperfecta but their parents were not. The etiological possibilities of germ mosaicism and the possibilities of an inheritance pattern different from the dominant one were discussed, which would give new genetic heterogeneity evidence.

  3. Novel missense loss-of-function mutations of WNT1 in an autosomal recessive Osteogenesis imperfecta patient.

    Science.gov (United States)

    Won, Joon Yeon; Jang, Woo Young; Lee, Hye-Ran; Park, Seon Young; Kim, Woo-Young; Park, Jong Hoon; Kim, Yonghwan; Cho, Tae-Joon

    2017-08-01

    Osteogenesis imperfecta (OI) is a heritable skeletal disorder characterized by bone fragility and low bone mass. Recently, loss-of-function mutations of WNT1 have been reported to be causative in OI or osteoporosis. We report an OI patient with novel compound heterozygous WNT1 missense mutations, p.Glu123Asp and p.Cys153Gly. Both mutations are found in the exon 3, and the p.Glu123Asp is the most proximal N-terminus missense mutation among the reported WNT1 missense mutations in OI patients. In vitro functional analysis reveals that while expression of wildtype WNT1 stimulates canonical WNT1-mediated β-catenin signaling, that of individual WNT1 mutant fails to do so, indicative of the pathogenic nature of the WNT1 variants. Although the pathogenic mechanism of WNT1 defects in OI has yet to be uncovered, these findings further contribute to the implications and importance of functional relevance of WNT1 in skeletal disorders. Copyright © 2017. Published by Elsevier Masson SAS.

  4. Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

    Science.gov (United States)

    DiGirolamo, Douglas J.; Singhal, Vandana; Chang, Xiaoli; Lee, Se-Jin; Germain-Lee, Emily L.

    2015-01-01

    Osteogenesis imperfecta (OI) comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI, many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B (ACVR2B) in a mouse model of type III OI (oim). Treatment of 12-week-old oim mice with ACVR2B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy, wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system. PMID:26161291

  5. Novel mutation of FKBP10 in a pediatric patient with osteogenesis imperfecta type XI identified by clinical exome sequencing

    Science.gov (United States)

    Velasco, Harvy Mauricio; Morales, Jessica L

    2017-01-01

    Osteogenesis imperfecta (OI) is a hereditary disease characterized by bone fragility caused by mutations in the proteins that support the formation of the extracellular matrix in the bone. The diagnosis of OI begins with clinical suspicion, from phenotypic findings at birth, low-impact fractures during childhood or family history that may lead to it. However, the variability in the semiology of the disease does not allow establishing an early diagnosis in all cases, and unfortunately, specific clinical data provided by the literature only report 28 patients with OI type XI. This information is limited and heterogeneous, and therefore, detailed information on the natural history of this disease is not yet available. This paper reports the case of a male patient who, despite undergoing multidisciplinary management, did not have a diagnosis for a long period of time, and could only be given one with the use of whole-exome sequencing. The use of the next-generation sequencing in patients with ultrarare genetic diseases, including skeletal dysplasias, should be justified when clear clinical criteria and an improvement in the quality of life of the patients and their families are intended while reducing economic and time costs. Thus, this case report corresponds to the 29th patient affected with OI type XI, and the 18th mutation in FKBP10, causative of this pathology. PMID:29158687

  6. Classification of micro-CT images using 3D characterization of bone canal patterns in human osteogenesis imperfecta

    Science.gov (United States)

    Abidin, Anas Z.; Jameson, John; Molthen, Robert; Wismüller, Axel

    2017-03-01

    Few studies have analyzed the microstructural properties of bone in cases of Osteogenenis Imperfecta (OI), or `brittle bone disease'. Current approaches mainly focus on bone mineral density measurements as an indirect indicator of bone strength and quality. It has been shown that bone strength would depend not only on composition but also structural organization. This study aims to characterize 3D structure of the cortical bone in high-resolution micro CT images. A total of 40 bone fragments from 28 subjects (13 with OI and 15 healthy controls) were imaged using micro tomography using a synchrotron light source (SRµCT). Minkowski functionals - volume, surface, curvature, and Euler characteristics - describing the topological organization of the bone were computed from the images. The features were used in a machine learning task to classify between healthy and OI bone. The best classification performance (mean AUC - 0.96) was achieved with a combined 4-dimensional feature of all Minkowski functionals. Individually, the best feature performance was seen using curvature (mean AUC - 0.85), which characterizes the edges within a binary object. These results show that quantitative analysis of cortical bone microstructure, in a computer-aided diagnostics framework, can be used to distinguish between healthy and OI bone with high accuracy.

  7. Children with severe Osteogenesis imperfecta and short stature present on average with normal IGF-I and IGFBP-3 levels.

    Science.gov (United States)

    Hoyer-Kuhn, Heike; Höbing, Laura; Cassens, Julia; Schoenau, Eckhard; Semler, Oliver

    2016-07-01

    Osteogenesis imperfecta (OI) is characterized by bone fragility and short stature. Data about IGF-I/IGFBP-3 levels are rare in OI. Therefore IGF-I/IGFBP-3 levels in children with different types of OI were investigated. IGF-I and IGFBP-3 levels of 60 children (male n=38) were assessed in a retrospective cross-sectional setting. Height/weight was significant different [height z-score type 3 versus type 4: p=0.0011 and weight (p≤0.0001)] between OI type 3 and 4. Mean IGF-I levels were in the lower normal range (mean±SD level 137.4±109.1 μg/L). Mean IGFBP-3 measurements were in the normal range (mean±SD 3.105±1.175 mg/L). No significant differences between OI type 3 and 4 children have been observed (IGF-I: p=0.0906; IGFBP-3: p=0.2042). Patients with different severities of OI have IGF-I and IGFBP-3 levels in the lower normal range. The type of OI does not significantly influence these growth factors.

  8. Delivery by Cesarean Section is not Associated With Decreased at-Birth Fracture Rates in Osteogenesis Imperfecta

    Science.gov (United States)

    Bellur, S; Jain, M; Cuthbertson, D; Krakow, D; Shapiro, JR; Steiner, RD; Smith, PA; Bober, MB; Hart, T; Krischer, J; Mullins, M; Byers, PH; Pepin, M; Durigova, M; Glorieux, FH; Rauch, F; Sutton, VR; Lee, B; Nagamani, SC

    2015-01-01

    Purpose Osteogenesis imperfecta (OI) predisposes to recurrent fractures. The moderate-to-severe forms of OI present with antenatal fractures and the mode of delivery that would be safest for the fetus is not known. Methods We conducted systematic analyses on the largest cohort of individuals (n=540) with OI enrolled to-date in the OI Linked Clinical Research Centers. Self-reported at-birth fracture rates were compared in individuals with OI types I, III, and IV. Multivariate analyses utilizing backward-elimination logistic regression model building were performed to assess the effect of multiple covariates including method of delivery on fracture-related outcomes. Results When accounting for other covariates, at-birth fracture rates did not differ based on whether delivery was by vaginal route or by cesarean section (CS). Increased birth weight conferred higher risk for fractures irrespective of the delivery method. In utero fracture, maternal history of OI, and breech presentation were strong predictors for choosing CS for delivery. Conclusion Our study, the largest to analyze the effect of various factors on at-birth fracture rates in OI shows that delivery by CS is not associated with decreased fracture rate. With the limitation that the fracture data were self-reported in this cohort, these results suggest that CS should be performed only for other maternal or fetal indications, but not for the sole purpose of fracture prevention in OI. PMID:26426884

  9. Geometry reconstruction method for patient-specific finite element models for the assessment of tibia fracture risk in osteogenesis imperfecta.

    Science.gov (United States)

    Caouette, Christiane; Ikin, Nicole; Villemure, Isabelle; Arnoux, Pierre-Jean; Rauch, Frank; Aubin, Carl-Éric

    2017-04-01

    Lower limb deformation in children with osteogenesis imperfecta (OI) impairs ambulation and may lead to fracture. Corrective surgery is based on empirical assessment criteria. The objective was to develop a reconstruction method of the tibia for OI patients that could be used as input of a comprehensive finite element model to assess fracture risks. Data were obtained from three children with OI and tibia deformities. Four pQCT scans were registered to biplanar radiographs, and a template mesh was deformed to fit the bone outline. Cortical bone thickness was computed. Sensitivity of the model to missing slices of pQCT was assessed by calculating maximal von Mises stress for a vertical hopping load case. Sensitivity of the model to ±5 % of cortical thickness measurements was assessed by calculating loads at fracture. Difference between the mesh contour and bone outline on the radiographs was below 1 mm. Removal of one pQCT slice increased maximal von Mises stress by up to 10 %. Simulated ±5 % variation of cortical bone thickness leads to variations of up to 4.1 % on predicted fracture loads. Using clinically available tibia imaging from children with OI, the developed reconstruction method allowed the building of patient-specific finite element models.

  10. Osteogenesis imperfecta type I: Molecular heterogeneity for COL1A1 null alleles of type I collagen

    Energy Technology Data Exchange (ETDEWEB)

    Willing, M.C.; Deschenes, S.P.; Pitts, S.H.; Arikat, H.; Roberts, E.J.; Scott, D.A.; Slayton, R.L. [Univ. of Iowa, Iowa City, IA (United States); Byers, P.H. [Univ. of Washington, Seattle, WA (United States)

    1994-10-01

    Osteogenesis imperfecta (OI) type I is the mildest form of inherited brittle-bone disease. Dermal fibroblasts from most affected individuals produce about half the usual amount of type I procollagen, as a result of a COL1A1 {open_quotes}null{close_quotes} allele. Using PCR amplification of genomic DNA from affected individuals, followed by denaturing gradient gel electrophoresis (DGGE) and SSCP, we identified seven different COL1A1 gene mutations in eight unrelated families with OI type I. Three families have single nucleotide substitutions that alter 5{prime} donor splice sites; two of these unrelated families have the same mutation. One family has a point mutation, in an exon, that creates a premature termination codon, and four have small deletions or insertions, within exons, that create translational frameshifts and new termination codons downstream of the mutation sites. Each mutation leads to both marked reduction in steady-state levels of mRNA from the mutant allele and a quantitative decrease in type I procollagen production. Our data demonstrate that different molecular mechanisms that have the same effect on type I collagen production result in the same clinical phenotype. 58 refs., 4 figs., 1 tab.

  11. Cardiopulmonary dysfunction in the Osteogenesis imperfecta mouse model Aga2 and human patients are caused by bone-independent mechanisms.

    Science.gov (United States)

    Thiele, Frank; Cohrs, Christian M; Flor, Armando; Lisse, Thomas S; Przemeck, Gerhard K H; Horsch, Marion; Schrewe, Anja; Gailus-Durner, Valerie; Ivandic, Boris; Katus, Hugo A; Wurst, Wolfgang; Reisenberg, Catherine; Chaney, Hollis; Fuchs, Helmut; Hans, Wolfgang; Beckers, Johannes; Marini, Joan C; Hrabé de Angelis, Martin

    2012-08-15

    Osteogenesis imperfecta (OI) is an inherited connective tissue disorder with skeletal dysplasia of varying severity, predominantly caused by mutations in the collagen I genes (COL1A1/COL1A2). Extraskeletal findings such as cardiac and pulmonary complications are generally considered to be significant secondary features. Aga2, a murine model for human OI, was systemically analyzed in the German Mouse Clinic by means of in vivo and in vitro examinations of the cardiopulmonary system, to identify novel mechanisms accounting for perinatal lethality. Pulmonary and, especially, cardiac fibroblast of perinatal lethal Aga2/+ animals display a strong down-regulation of Col1a1 transcripts in vivo and in vitro, resulting in a loss of extracellular matrix integrity. In addition, dysregulated gene expression of Nppa, different types of collagen and Agt in heart and lung tissue support a bone-independent vicious cycle of heart dysfunction, including hypertrophy, loss of myocardial matrix integrity, pulmonary hypertension, pneumonia and hypoxia leading to death in Aga2. These murine findings are corroborated by a pediatric OI cohort study, displaying significant progressive decline in pulmonary function and restrictive pulmonary disease independent of scoliosis. Most participants show mild cardiac valvular regurgitation, independent of pulmonary and skeletal findings. Data obtained from human OI patients and the mouse model Aga2 provide novel evidence for primary effects of type I collagen mutations on the heart and lung. The findings will have potential benefits of anticipatory clinical exams and early intervention in OI patients.

  12. Osteochondritis dissecans of the lateral femoral condyle in a patient affected by osteogenesis imperfecta: a case report.

    Science.gov (United States)

    Persiani, Pietro; Di Domenica, Marica; Martini, Lorena; Ranaldi, Filippo M; Zambrano, Anna; Celli, Mauro; Villani, Ciro

    2015-11-01

    Osteochondritis dissecans is a very uncommon phenomenon in osteogenesis imperfecta (OI). A 14-year-old boy, affected by OI and followed in our Center for Congenital Osteodystrophies, had a knee trauma and MRI indicated a hollowed area of 2.5×1.5 cm in the lateral femoral condyle, which was classified as grade III. The patient underwent surgery, performed as a one-step surgical treatment: the osteochondral fragment was removed, curettage of lesion's bottom was performed, and a biphasic scaffold was used to fill the defect, implanted with a press-fit technique. MRI at 12 and 24 months after surgery showed scaffold integration. At the final follow-up, the patient did not feel any pain or articular limitations. It is difficult to provide a guideline on osteochondritis dissecans in patients affected by OI because of the lack of literature reports on this rare disorder in a rare disease. According to our experience, in these patients, osteosynthesis of the bone fragment and the use of autograft are not recommended because of the patient's bone weakness and osteoporosis. Moreover, compared with two-step surgery, one-step surgery is preferred to reduce the risk related to anesthesia, often observed to be higher in these patients.

  13. A novel de novo COL1A1 mutation in a Thai boy with osteogenesis imperfecta born to consanguineous parents

    Directory of Open Access Journals (Sweden)

    Siraprapa Tongkobpetch

    2017-09-01

    Full Text Available Abstract Osteogenesis imperfecta (OI is genetically heterogeneous. Mutations in COL1A1 and COL1A2 are responsible for at least 90% of the cases, which are transmitted in an autosomal dominant manner or are de novo events. We identified a Thai boy with OI whose parents were first cousins. Because the proband was the product of a consanguineous marriage, we hypothesized that he might be homozygous for a mutation in a known gene causing a recessive form of OI. Using whole exome sequencing (WES, we did not find any pathogenic mutations in any known gene responsible for an autosomal recessive form of OI. Instead, we identified a COL1A1 frameshift mutation, c.1290delG (p.Gly431Valfs*110 in heterozygosis. By Sanger sequencing, the mutation was confirmed in the proband, and not detected in his parents, indicating that it was a de novo mutation. These findings had implication for genetic counseling. In conclusion, we expanded the mutational spectrum of COL1A1 and provided another example of a de novo pathogenic mutation in heterozygosis in a patient born to consanguineous parents.

  14. Identification of a candidate mutation in the COL1A2 gene of a Chow Chow with osteogenesis imperfecta.

    Science.gov (United States)

    Quist, E M; Doan, R; Pool, R R; Porter, B F; Bannasch, D L; Dindot, S V

    2017-09-19

    Osteogenesis imperfecta (OI) is a genetic disease that occurs in humans and animals. Individuals with OI exhibit signs of extreme bone fragility and osteopenia with frequent fractures and perinatal lethality in severe cases. In this study, we report the clinical diagnosis of OI in a dog and the use targeted next-generation sequencing to identify a candidate autosomal dominant mutation in the COL1A2 gene. A five-month old male Chow Chow was examined with a fractured left humerus and resolving, bilateral femoral fractures. Radiographs revealed generalized osteopenia and bilateral humeral, radial, and femoral fractures. Targeted next-generation sequencing of genes associated with OI in humans (COL1A1, COL1A2, LEPRE1, SERPINH1, and CRTAP) revealed a G>A heterozygous mutation in the splice donor site of exon 18 of the COL1A2 gene (c.936+1G>A). The splice donor mutation was not detected among 91 control dogs representing 21 breeds. A comparative analysis of exon 18 and the exon-intron junction further showed that the mutated splice donor site is conserved among vertebrates. Altogether, these findings reveal a candidate autosomal splice donor site mutation causing OI in an individual Chow Chow. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Two novel distinct COL1A2 mutations highlight the complexity of genotype-phenotype correlations in osteogenesis imperfecta and related connective tissue disorders.

    Science.gov (United States)

    Reuter, Miriam S; Schwabe, Georg C; Ehlers, Christian; Marschall, Christoph; Reis, André; Thiel, Christian; Graul-Neumann, Luitgard

    2013-12-01

    Osteogenesis imperfecta is a heritable connective tissue disorder characterized by variable symptoms including predisposition to fractures. Despite the identification of numerous mutations, a reliable genotype-phenotype correlation has remained notoriously difficult. We now describe two patients with osteogenesis imperfecta and novel, so far undescribed mutations in the COL1A2 gene, further highlighting this complexity. A 3-year-old patient presented with features reminiscent of a connective tissue disorder, with joint hypermobility, Wormian bones, streaky lucencies in the long bones and relative macrocephaly. The patient carried a heterozygous c.1316G > A (p.Gly439Asp) mutation in the COL1A2 gene located in a triple-helix region, in which glycine substitutions have been assumed to cause perinatal lethal OI (Sillence type II). A second family with type I osteogenesis imperfecta carried a heterozygous nonsense mutation c.4060C > T (p.Gln1354X) within the last exon of COL1A2. Whereas other heterozygous nonsense mutations in COL1A2 do not lead to a phenotype, in this case the mRNA is presumed to escape nonsense-mediated decay. Therefore the predicted COL1A2 propeptide lacks the last 13 C-terminal amino acids, suggesting that the OI phenotype results from decelerated assembly and overmodification of the collagen triple helix. The presented COL1A2 mutations exemplify the complexity of COL1A2 genotype-phenotype correlation in genetic counselling in OI. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. ENDOPLASMIC RETICULUM-MEDIATED QUALITY-CONTROL OF TYPE-I COLLAGEN PRODUCTION BY CELLS FROM OSTEOGENESIS IMPERFECTA PATIENTS WITH MUTATIONS IN THE PRO-ALPHA-1(I) CHAIN CARBOXYL-TERMINAL PROPEPTIDE WHICH IMPAIR SUBUNIT ASSEMBLY

    NARCIS (Netherlands)

    LAMANDE, [No Value; CHESSLER, SD; GOLUB, SB; BYERS, PH; CHAN, D; COLE, WG; SILLENCE, DO; BATEMAN, JF

    1995-01-01

    A heterozygous single base change in exon 49 of COL1A1, which converted the codon for pro alpha 1(I) carboxyl-terminal propeptide residue 94 from tryptophan (TGG) to cysteine (TGT) was identified in a baby with lethal osteogenesis imperfecta (OI64). The C-propeptide mutations in OI64 and in another

  17. The phenotypic features of osteogenesis imperfecta resulting from a mutation of the carboxyl-terminal pro alpha 1(I) propeptide that impairs the assembly of type I procollagen and formation of the extracellular matrix

    NARCIS (Netherlands)

    Cole, WG; Chow, CW; Bateman, JF; Sillence, DO

    1996-01-01

    The features of a baby with lethal perinatal osteogenesis imperfecta (OI-II), resulting from the substitution of tryptophan 94 by cysteine in the carboxyl-terminal propeptide of pro alpha 1(I) chains of type I procollagen, were studied. The limbs and torso were of normal length, shape, and

  18. Kohlschütter-Tönz syndrome: mutations in ROGDI and evidence of genetic heterogeneity

    NARCIS (Netherlands)

    Tucci, Arianna; Kara, Eleanna; Schossig, Anna; Wolf, Nicole I.; Plagnol, Vincent; Fawcett, Katherine; Paisán-Ruiz, Coro; Moore, Matthew; Hernandez, Dena; Musumeci, Sebastiano; Tennison, Michael; Hennekam, Raoul; Palmeri, Silvia; Malandrini, Alessandro; Raskin, Salmo; Donnai, Dian; Hennig, Corina; Tzschach, Andreas; Hordijk, Roel; Bast, Thomas; Wimmer, Katharina; Lo, Chien-Ning; Shorvon, Simon; Mefford, Heather; Eichler, Evan E.; Hall, Roger; Hayes, Ian; Hardy, John; Singleton, Andrew; Zschocke, Johannes; Houlden, Henry

    2013-01-01

    Kohlschütter-Tönz syndrome (KTS) is a rare autosomal recessive disorder characterized by amelogenesis imperfecta, psychomotor delay or regression and seizures starting early in childhood. KTS was established as a distinct clinical entity after the first report by Kohlschütter in 1974, and to date,

  19. KohlschutterTonz Syndrome: Mutations in ROGDI and Evidence of Genetic Heterogeneity

    NARCIS (Netherlands)

    Tucci, A.; Kara, E.; Schossig, A.; Wolf, N.I.; Plagnol, V.; Fawcett, K.; Paisan-Ruiz, C.; Moore, M.; Hernandez, D.; Musumeci, S.; Tennison, M.; Hennekam, R.; Palmeri, S.; Malandrini, A.; Raskin, S.; Donnai, D.; Hennig, C.; Tzschach, A.; Hordijk, R.; Bast, T.; Wimmer, K.; Lo, C.N.; Shorvon, S.; Mefford, H.; Eichler, E.E.; Hall, R.; Hayes, I.; Hardy, J.; Singleton, A.; Zschocke, J.; Houlden, H.

    2013-01-01

    Kohlschütter-Tönz syndrome (KTS) is a rare autosomal recessive disorder characterized by amelogenesis imperfecta, psychomotor delay or regression and seizures starting early in childhood. KTS was established as a distinct clinical entity after the first report by Kohlschütter in 1974, and to date,

  20. KohlschutterTonz Syndrome : Mutations in ROGDI and Evidence of Genetic Heterogeneity

    NARCIS (Netherlands)

    Tucci, Arianna; Kara, Eleanna; Schossig, Anna; Wolf, Nicole I.; Plagnol, Vincent; Fawcett, Katherine; Paisan-Ruiz, Coro; Moore, Matthew; Hernandez, Dena; Musumeci, Sebastiano; Tennison, Michael; Hennekam, Raoul; Palmeri, Silvia; Malandrini, Alessandro; Raskin, Salmo; Donnai, Dian; Hennig, Corina; Tzschach, Andreas; Hordijk, Roel; Bast, Thomas; Wimmer, Katharina; Lo, Chien-Ning; Shorvon, Simon; Mefford, Heather; Eichler, Evan E.; Hall, Roger; Hayes, Ian; Hardy, John; Singleton, Andrew; Zschocke, Johannes; Houlden, Henry

    KohlschutterTonz syndrome (KTS) is a rare autosomal recessive disorder characterized by amelogenesis imperfecta, psychomotor delay or regression and seizures starting early in childhood. KTS was established as a distinct clinical entity after the first report by Kohlschutter in 1974, and to date,

  1. SLC13A5 is the second gene associated with Kohlschutter-Tonz syndrome

    NARCIS (Netherlands)

    Schossig, A.; Bloch-Zupan, A.; Lussi, A.; Wolf, N.I.; Raskin, S.; Cohen, M.; Giuliano, F.; Jurgens, J.; Krabichler, B.; Koolen, D.A.; Sobreira, N.L.; Maurer, E.; Muller-Bolla, M.; Penzien, J.; Zschocke, J.; Kapferer-Seebacher, I.

    2017-01-01

    BACKGROUND: Kohlschutter-Tonz syndrome (KTZS) is a rare autosomal-recessive disease characterised by epileptic encephalopathy, intellectual disability and amelogenesis imperfecta (AI). It is frequently caused by biallelic mutations in ROGDI. Here, we report on individuals with ROGDI-negative KTZS

  2. Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.

    Science.gov (United States)

    Jacobsen, Christina M; Schwartz, Marissa A; Roberts, Heather J; Lim, Kyung-Eun; Spevak, Lyudmila; Boskey, Adele L; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

    2016-09-01

    Osteogenesis Imperfecta (OI) comprises a group of genetic skeletal fragility disorders. The mildest form of OI, Osteogenesis Imperfecta type I, is frequently caused by haploinsufficiency mutations in COL1A1, the gene encoding the α1(I) chain of type 1 collagen. Children with OI type I have a 95-fold higher fracture rate compared to unaffected children. Therapies for OI type I in the pediatric population are limited to anti-catabolic agents. In adults with osteoporosis, anabolic therapies that enhance Wnt signaling in bone improve bone mass, and ongoing clinical trials are determining if these therapies also reduce fracture risk. We performed a proof-of-principle experiment in mice to determine whether enhancing Wnt signaling in bone could benefit children with OI type I. We crossed a mouse model of OI type I (Col1a1(+/Mov13)) with a high bone mass (HBM) mouse (Lrp5(+/p.A214V)) that has increased bone strength from enhanced Wnt signaling. Offspring that inherited the OI and HBM alleles had higher bone mass and strength than mice that inherited the OI allele alone. However, OI+HBM and OI mice still had bones with lower ductility compared to wild-type mice. We conclude that enhancing Wnt signaling does not make OI bone normal, but does improve bone properties that could reduce fracture risk. Therefore, agents that enhance Wnt signaling are likely to benefit children and adults with OI type 1. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Mutation in a gene for type I procollagen (COL1A2) in a woman with postmenopausal osteoporosis: Evidence for phenotypic and genotypic overlap with mild osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Spotila, L.D.; Constantinou, C.D.; Sereda, L.; Ganguly, A.; Prockop, D.J. (Jefferson Medical College, Philadelphia, PA (United States)); Riggs, B.L. (Mayo Clinic, Rochester, MN (United States))

    1991-06-15

    Mutations in the two genes for type I collagen (COL1A1 or COL1A2) cause osteogenesis imperfecta (OI), a heritable disease characterized by moderate to extreme brittleness of bone early in life. Here, the authors show that a 52-year-old post menopausal woman with severe osteopenia and a compression fracture of a thoracic vertebra had a mutation in the gene for the {alpha}2(I) chain of type I collagen (COL1A2) similar to mutations that cause OI. cDNA was prepared from the woman's skin fibroblast RNA and assayed for the presence of a mutation by treating DNA heteroduplexes with carbodiimide. The results indicated a sequence variation in the region encoding amino acid residues 660-667 of the {alpha}2(I) chain. Further analysis demonstrated a single-base mutation that caused a serine-for-glycine substitution at position 661 of the {alpha}2(I) triple-helical domain. The substitution produced posttranslational overmodification of the collagen triple helix, as is seen with most glycine substitutions that cause OI. The patient had a history of five previous fractures, slightly blue sclerae, and slight hearing loss. Therefore, the results suggest that there may be phenotypic and genotypic overlap between mild osteogenesis imperfecta and postmenopausal osteoporosis, and that a subset of women with postmenopausal osteoporosis may have mutations in the genes for type I procollagen.

  4. Recurrent Proximal Femur Fractures in a Teenager With Osteogenesis Imperfecta on Continuous Bisphosphonate Therapy: Are We Overtreating?

    Science.gov (United States)

    Vasanwala, Rashida F; Sanghrajka, Anish; Bishop, Nicholas J; Högler, Wolfgang

    2016-07-01

    Long-term bisphosphonate (BP) therapy in adults with osteoporosis is associated with atypical femoral fractures, caused by increased material bone density and prolonged suppression of bone remodeling which may reduce fracture toughness. In children with osteogenesis imperfecta (OI), long-term intravenous BP therapy improves bone structure and mass without further increasing the already hypermineralized bone matrix, and is generally regarded as safe. Here we report a teenage girl with OI type IV, who was started on cyclical intravenous pamidronate therapy at age 6 years because of recurrent fractures. Transiliac bone biopsy revealed classical structural features of OI but unusually low bone resorption surfaces. She made substantial improvements in functional ability, bone mass, and fracture rate. However, after 5 years of pamidronate therapy she started to develop recurrent, bilateral, nontraumatic, and proximal femur fractures, which satisfied the case definition for atypical femur fractures. Some fractures were preceded by periosteal reactions and prodromal pain. Pamidronate was discontinued after 7 years of therapy, following which she sustained two further nontraumatic femur fractures, and continued to show delayed tibial osteotomy healing. Despite rodding surgery, and very much in contrast to her affected, untreated, and normally mobile mother, she remains wheelchair-dependent. The case of this girl raises questions about the long-term safety of BP therapy in some children, in particular about the risk of oversuppressed bone remodeling with the potential for microcrack accumulation, delayed healing, and increased stiffness. The principal concern is whether there is point at which benefit from BP therapy could turn into harm, where fracture risk increases again. This case should stimulate debate whether current adult atypical femoral fracture guidance should apply to children, and whether low-frequency, low-dose cyclical, intermittent, or oral treatment

  5. A nonclassical IFITM5 mutation located in the coding region causes severe osteogenesis imperfecta with prenatal onset.

    Science.gov (United States)

    Hoyer-Kuhn, Heike; Semler, Oliver; Garbes, Lutz; Zimmermann, Katharina; Becker, Jutta; Wollnik, Bernd; Schoenau, Eckhard; Netzer, Christian

    2014-06-01

    Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder characterized by a wide range of skeletal symptoms. Most patients have dominantly inherited or de novo mutations in COL1A1 or COL1A2. Up to 5% of patients have OI type V, characterized by hyperplastic callus formation after fractures, calcification of the interosseous membrane of the forearm, and a mesh-like lamellation pattern observed in bone histology. Recently, a heterozygous mutation in the 5'-untranslated region (UTR) of IFITM5 (c.-14C > T) was identified as the underlying cause of OI type V, and only this specific mutation was subsequently identified in all patient cohorts with this OI subtype. We now present a case of a heterozygous mutation within the coding region of IFITM5 (c.119C > T; p.S40L). The mutation occurred de novo in the patient and resulted in severe OI with prenatal onset and extreme short stature. At the age of 19 months, the typical clinical hallmarks of OI type V were not present. Our finding has important consequences for the genetic "work-up" of patients suspected to have OI, both in prenatal and in postnatal settings: The entire gene-not only the 5'-UTR harboring the "classical" OI type V mutation-has to be analyzed to exclude a causal role of IFITM5. We propose that this should be part of the initial diagnostic steps for genetic laboratories performing SANGER sequencing in OI patients. © 2014 American Society for Bone and Mineral Research.

  6. Pre- and postnatal transplantation of fetal mesenchymal stem cells in osteogenesis imperfecta: a two-center experience.

    Science.gov (United States)

    Götherström, Cecilia; Westgren, Magnus; Shaw, S W Steven; Aström, Eva; Biswas, Arijit; Byers, Peter H; Mattar, Citra N Z; Graham, Gail E; Taslimi, Jahan; Ewald, Uwe; Fisk, Nicholas M; Yeoh, Allen E J; Lin, Ju-Li; Cheng, Po-Jen; Choolani, Mahesh; Le Blanc, Katarina; Chan, Jerry K Y

    2014-02-01

    Osteogenesis imperfecta (OI) can be recognized prenatally with ultrasound. Transplantation of mesenchymal stem cells (MSCs) has the potential to ameliorate skeletal damage. We report the clinical course of two patients with OI who received prenatal human fetal MSC (hfMSC) transplantation and postnatal boosting with same-donor MSCs. We have previously reported on prenatal transplantation for OI type III. This patient was retransplanted with 2.8 × 10(6) same-donor MSCs per kilogram at 8 years of age, resulting in low-level engraftment in bone and improved linear growth, mobility, and fracture incidence. An infant with an identical mutation who did not receive MSC therapy succumbed at 5 months despite postnatal bisphosphonate therapy. A second fetus with OI type IV was also transplanted with 30 × 10(6) hfMSCs per kilogram at 31 weeks of gestation and did not suffer any new fractures for the remainder of the pregnancy or during infancy. The patient followed her normal growth velocity until 13 months of age, at which time longitudinal length plateaued. A postnatal infusion of 10 × 10(6) MSCs per kilogram from the same donor was performed at 19 months of age, resulting in resumption of her growth trajectory. Neither patient demonstrated alloreactivity toward the donor hfMSCs or manifested any evidence of toxicities after transplantation. Our findings suggest that prenatal transplantation of allogeneic hfMSCs in OI appears safe and is of likely clinical benefit and that retransplantation with same-donor cells is feasible. However, the limited experience to date means that it is not possible to be conclusive and that further studies are required.

  7. Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial.

    Science.gov (United States)

    Plante, Laura; Veilleux, Louis-Nicolas; Glorieux, Francis H; Weiler, Hope; Rauch, Frank

    2016-05-01

    Osteogenesis imperfecta (OI) is a heritable condition characterized by fragile bones. Our previous studies indicated that serum 25-hydroxyvitamin D (25OHD) concentrations were positively associated with lumbar spine areal bone mineral density (LS-aBMD) in children and adolescents with OI. Here we assessed whether one year of high-dose vitamin D supplementation results in higher LS-aBMD z-scores in youth with OI. A one-year double-blind randomized controlled trial conducted at a pediatric orthopedic hospital in Montreal, Canada. Sixty patients (age: 6.0 to 18.9years; 35 female) were randomized in equal numbers to receive either 400 or 2000international units (IU) of vitamin D, stratified according to baseline bisphosphonate treatment status and pubertal stage. At baseline, the average serum 25OHD concentration was 65.6nmol/L (SD 20.4) with no difference between treatment groups (p=0.77); 21% of patients had results <50nmol/L. Vitamin D supplementation was associated with higher serum 25OHD concentrations in 90% of participants. The increase in mean 25OHD was significantly higher (p=0.02) in the group receiving 2000IU of vitamin D (mean [95% CI]=30.5nmol/L [21.3; 39.6]) than in the group receiving 400IU (15.2nmol/L [6.4; 24.1]). No significant differences in LS-aBMD z-score changes were detected between treatment groups. Thus, supplementation with vitamin D at 2000IU increased serum 25OHD concentrations in children with OI more than supplementation with 400IU. However, in this study where about 80% of participants had baseline serum 25OHD concentrations ≥50nmol/L, this difference had no detectable effect on LS-aBMD z-scores. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Combination sclerostin antibody and zoledronic acid treatment outperforms either treatment alone in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Little, David G; Peacock, Lauren; Mikulec, Kathy; Kneissel, Michaela; Kramer, Ina; Cheng, Tegan L; Schindeler, Aaron; Munns, Craig

    2017-08-01

    In this study, we examined the therapeutic potential of anti-Sclerostin Antibody (Scl-Ab) and bisphosphonate treatments for the bone fragility disorder Osteogenesis Imperfecta (OI). Mice with the Amish OI mutation (Col1a2 G610C mice) and control wild type littermates (WT) were treated from week 5 to week 9 of life with (1) saline (control), (2) zoledronic acid given 0.025mg/kg s.c. weekly (ZA), (3) Scl-Ab given 50mg/kg IV weekly (Scl-Ab), or (4) a combination of both (Scl-Ab/ZA). Functional outcomes were prioritized and included bone mineral density (BMD), bone microarchitecture, long bone bending strength, and vertebral compression strength. By dual-energy absorptiometry, Scl-Ab treatment alone had no effect on tibial BMD, while ZA and Scl-Ab/ZA significantly enhanced BMD by week 4 (+16% and +27% respectively, P<0.05). Scl-Ab/ZA treatment also led to increases in cortical thickness and tissue mineral density, and restored the tibial 4-point bending strength to that of control WT mice. In the spine, all treatments increased compression strength over controls, but only the combined group reached the strength of WT controls. Scl-Ab showed greater anabolic effects in the trabecular bone than in cortical bone. In summary, the Scl-Ab/ZA intervention was superior to either treatment alone in this OI mouse model, however further studies are required to establish its efficacy in other preclinical and clinical scenarios. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  9. Bone Marrow Stromal Cells Contribute to Bone Formation Following Infusion into Femoral Cavities of a Mouse Model of Osteogenesis Imperfecta

    Science.gov (United States)

    Li, Feng; Wang, Xujun; Niyibizi, Christopher

    2010-01-01

    Currently, there are conflicting data in literature regarding contribution of bone marrow stromal cells (BMSCs) to bone formation when the cells are systemically delivered in recipient animals. To understand if BMSCs contribute to bone cell phenotype and bone formation in osteogenesis imperfecta bones (OI), MSCs marked with GFP were directly infused into the femurs of a mouse model of OI (oim). The contribution of the cells to the cell phenotype and bone formation was assessed by histology, immunohistochemistry and biomechanical loading of recipient bones. Two weeks following infusion of BMSCs, histological examination of the recipient femurs demonstrated presence of new bone when compared to femurs injected with saline which showed little or no bone formation. The new bone contained few donor cells as demonstrated by GFP fluorescence. At six weeks following cell injection, new bone was still detectable in the recipient femurs but was enhanced by injection of the cells suspended in pepsin solublized type I collagen. Immunofluorescence and immunohistochemical staining showed that donor GFP positive cells in the new bone were localized with osteocalcin expressing cells suggesting that the cells differentiated into osteoblasts in vivo. Biomechanical loading to failure in thee point bending, revealed that, femurs infused with BMSCs in PBS or in soluble type I collagen were biomechanically stronger than those injected with PBS or type I collagen alone. Taken together, the results indicate that transplanted cells differentiated into osteoblasts in vivo and contributed to bone formation in vivo; we also speculate that donor cells induced differentiation or recruitment of endogenous cells to initiate reparative process at early stages following transplantation. PMID:20570757

  10. Tissue level material composition and mechanical properties in Brtl/+ mouse model of Osteogenesis Imperfecta after sclerostin antibody treatment

    Science.gov (United States)

    Lloyd, William R.; Sinder, Benjamin P.; Salemi, Joseph; Ominsky, Michael S.; Marini, Joan C.; Caird, Michelle S.; Morris, Michael D.; Kozloff, Kenneth M.

    2015-02-01

    Osteogenesis imperfecta (OI) is a genetic disorder resulting in defective collagen or collagen-associated proteins and fragile, brittle bones. To date, therapies to improve OI bone mass, such as bisphosphonates, have increased bone mass in the axial skeleton of OI patients, but have shown limited effects at reducing long bone fragility. Sclerostin antibody (Scl- Ab), currently in clinical trials for osteoporosis, stimulates bone formation and may have the potential to reduce long bone fracture rates in OI patients. Scl-Ab has been investigated as an anabolic therapy for OI in the Brtl/+ mouse model of moderately severe Type IV OI. While Scl-Ab increases long bone mass in the Brtl/+ mouse, it is not known whether material properties and composition changes also occur. Here, we report on the effects of Scl-Ab on wild type and Brtl/+ young (3 week) and adult (6 month) male mice. Scl-Ab was administered over 5 weeks (25mg/kg, 2x/week). Raman microspectroscopy and nanoindentation are used for bone composition and biomechanical bone property measurements in excised bone. Fluorescent labels (calcein and alizarin) at 4 time points over the entire treatment period are used to enable measurements at specific tissue age. Differences between wild type and Brtl/+ groups included variations in the mineral and matrix lattices, particularly the phosphate v1, carbonate v1, and the v(CC) proline and hydroxyproline stretch vibrations. Results of Raman spectroscopy corresponded to nanoindentation findings which indicated that old bone (near midcortex) is stiffer (higher elastic modulus) than new bone. We compare and contrast mineral to matrix and carbonate to phosphate ratios in young and adult mice with and without treatment.

  11. Molecular Consequences of the SERPINH1/HSP47 Mutation in the Dachshund Natural Model of Osteogenesis Imperfecta.

    Science.gov (United States)

    Lindert, Uschi; Weis, Mary Ann; Rai, Jyoti; Seeliger, Frank; Hausser, Ingrid; Leeb, Tosso; Eyre, David; Rohrbach, Marianne; Giunta, Cecilia

    2015-07-17

    Osteogenesis imperfecta (OI) is a heritable connective tissue disease characterized by bone fragility and increased risk of fractures. Up to now, mutations in at least 18 genes have been associated with dominant and recessive forms of OI that affect the production or post-translational processing of procollagen or alter bone homeostasis. Among those, SERPINH1 encoding heat shock protein 47 (HSP47), a chaperone exclusive for collagen folding in the ER, was identified to cause a severe form of OI in dachshunds (L326P) as well as in humans (one single case with a L78P mutation). To elucidate the disease mechanism underlying OI in the dog model, we applied a range of biochemical assays to mutant and control skin fibroblasts as well as on bone samples. These experiments revealed that type I collagen synthesized by mutant cells had decreased electrophoretic mobility. Procollagen was retained intracellularly with concomitant dilation of ER cisternae and activation of the ER stress response markers GRP78 and phospho-eIF2α, thus suggesting a defect in procollagen processing. In line with the migration shift detected on SDS-PAGE of cell culture collagen, extracts of bone collagen from the OI dog showed a similar mobility shift, and on tandem mass spectrometry, the chains were post-translationally overmodified. The bone collagen had a higher content of pyridinoline than control dog bone. We conclude that the SERPINH1 mutation in this naturally occurring model of OI impairs how HSP47 acts as a chaperone in the ER. This results in abnormal post-translational modification and cross-linking of the bone collagen. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. A method distinguishing expressed vs. null mutations of the Col1A1 gene in osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Redford-Badwal, D.A.; Stover, M.L.; McKinstry, M. [and others

    1994-09-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of heritable disorders of bone characterized by increased susceptibility to fracture. Most of the causative mutations were identified in patients with the lethal form of the disease. Attention is now shifting to the milder forms of OI where glycine substitutions and null producing mutations have been found. Single amino acid substitutions can be identified by RT/PCR of total cellular RNA, but this approach does not work well for null mutations since the defective transcript does not accumulate in the cytoplasm. We have altered our RNA extraction method to separate RNA from the nuclear and cytoplasmic compartments of cultured fibroblasts. Standard methods of mutation identification (RT/PCR followed by SSCP) is applied to each RNA fraction. DNA from an abnormal band on the SSCP gel is eluted and amplified by PCR for cloning and sequencing. Using this approach we have identified an Asp to Asn change in exon 50 (type II OI) and a Gly to Arg in exon 11 (type I OI) of the COL1A1 gene. These changes were found in both nuclear and cytoplasmic compartments. These putative mutations are currently being confirmed by protein studies. In contrast, three patients with mild OI associated with reduced {proportional_to}(I)mRNA, had distinguishing SSCP bands present in the nuclear but not the cytoplasmic compartment. In one case a frame shift mutation was observed, while the other two revealed polymorphisms. The compartmentalization of the mutant allele has directed us to look elsewhere in the transcript for the causative mutation. This approach to mutation identification is capable of distinguishing these fundamentally different types of mutations and allows for preferential cloning and sequencing of the abnormal allele.

  13. Sclerostin antibody treatment improves the bone phenotype of Crtap−/− mice, a model of recessive Osteogenesis Imperfecta

    Science.gov (United States)

    Grafe, Ingo; Alexander, Stefanie; Yang, Tao; Lietman, Caressa; Homan, Erica P; Munivez, Elda; Chen, Yuqing; Jiang, Ming Ming; Bertin, Terry; Dawson, Brian; Asuncion, Franklin; Ke, Hua Zhu; Ominsky, Michael S; Lee, Brendan

    2016-01-01

    Osteogenesis Imperfecta (OI) is characterized by low bone mass, poor bone quality and fractures. Standard treatment for OI patients is limited to bisphosphonates, which only incompletely correct the bone phenotype, and seem to be less effective in adults. Sclerostin neutralizing antibodies (Scl-Ab) have been shown to be beneficial in animal models of osteoporosis, and dominant OI resulting from mutations in the genes encoding type I collagen. However, Scl-Ab treatment has not been studied in models of recessive OI. Cartilage associated protein (CRTAP) is involved in posttranslational type I collagen modification, and its loss of function results in recessive OI. In this study, we treated 1 and 6 week old Crtap−/− mice with Scl-Ab for 6 weeks (25 mg/kg, s.c., twice per week), to determine the effects on the bone phenotype in models of “pediatric” and “young adult” recessive OI. Vehicle treated Crtap−/− and wildtype (WT) mice served as controls. Compared with control Crtap−/− mice, microCT analyses showed significant increases in bone volume and improved trabecular microarchitecture in Scl-Ab treated Crtap−/− mice in both age cohorts, in both vertebrae and femurs. Additionally, Scl-Ab improved femoral cortical parameters in both age cohorts. Biomechanical testing showed that Scl-Ab improved parameters of whole bone strength in Crtap−/− mice, with more robust effects in the week 6–12 cohort, but did not affect the increased bone brittleness. Additionally, Scl-Ab normalized the increased osteoclast numbers, stimulated bone formation rate (week 6–12 cohort only), but did not affect osteocyte density. Overall, our findings suggest that Scl-Ab treatment may be beneficial in the treatment of recessive OI caused by defects in collagen post-translational modification. PMID:26716893

  14. Single dose of bisphosphonate preserves gains in bone mass following cessation of sclerostin antibody in Brtl/+ osteogenesis imperfecta model.

    Science.gov (United States)

    Perosky, Joseph E; Khoury, Basma M; Jenks, Terese N; Ward, Ferrous S; Cortright, Kai; Meyer, Bethany; Barton, David K; Sinder, Benjamin P; Marini, Joan C; Caird, Michelle S; Kozloff, Kenneth M

    2016-12-01

    Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3week old Brtl/+ and wild type mice for 5weeks with SclAb, and then withdrew treatment for an additional 6weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl/+ murine model of OI, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6weeks following cessation. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Corrective osteotomy with retrograde Fassier-Duval nail in an osteogenesis imperfecta patient with bilateral genu valgum: A case report.

    Science.gov (United States)

    Lin, Tsung-Yu; Yang, Chen-Yu; Liu, Shih-Chia

    2017-11-01

    The treatment of osteogenesis imperfecta (OI) requires a multidisciplinary approach to maximize function and reduce fracture incidence. The aim of this case report was to discuss an alternative surgical approach to stabilize a corrective osteotomy using the Fassier Duval (FD) system in an OI patient. A 20-year-old OI woman presented with left thigh pain, gait disturbance, and bilateral genu valgus deformities. Physical examination and standing radiographs revealed bilateral genu valgum with previous fixation implants in the femoral and the left tibia. Staged surgery was performed. A previous Ender pin was removed from the left femur, and a FD nail was inserted in a retrograde fashion. An intercondylar fracture was encountered while inserting the female rod in the distal left femur. After removal of a previous Rush pin from the right femur, several complications were also encountered during FD nailing of the right femur. The tip threads of the FD male nail could not achieve adequate anchorage in the region of the greater trochanter. To prevent male nail dropping, a horizontal stop Kirschner pin was inserted close to the distal end of the female nail. Despite perioperative problems such as rod dropping and occurrence of an intercondylar fracture of the left distal femur, bilateral retrograde nailing using the FD system was successful. An accurate entry portal is important when performing retrograde rodding. In addition, reaming the portal to a larger diameter in order to accommodate the large head of the female nail can prevent intraoperative intercondylar split, especially when combined with an osteotomy at the distal femur. Selection of the proper surgical technique is dependent on both the surgeon's experience and the condition of the patient. Although not an optimal device, a FD nail can be used as an IM nail for corrective osteotomy at the distal femur in an adult OI patient with a small femoral IM canal. Copyright © 2017 The Authors. Published by Wolters

  16. Incidence of Fractures From Perioperative Blood Pressure Cuff Use, Tourniquet Use, and Patient Positioning in Osteogenesis Imperfecta.

    Science.gov (United States)

    Sullivan, Brian T; Margalit, Adam; Garg, Vaibhav S; Njoku, Dolores B; Sponseller, Paul D

    2017-11-16

    Osteogenesis imperfecta (OI) is a rare connective tissue disease with varying severity. Patients with OI are highly susceptible to skeletal fractures. Optimal perioperative management of these patients is not well defined. We investigated the risks associated with intraoperative use of noninvasive blood pressure (NIBP) cuffs, tourniquets, and intra-arterial catheters, and patient positioning in children with OI. We retrospectively reviewed records of patients younger than 21 years with OI who underwent surgery with general anesthesia from 2010 to 2016 at our tertiary care center. The primary outcome of interest was iatrogenic fracture caused by NIBP cuff use, tourniquet use, or patient positioning. The secondary outcome of interest was complications associated with intra-arterial catheter use. Thirty-seven patients (15 girls) with a mean age of 10±4.8 years underwent 96 orthopaedic procedures (lower extremity, upper extremity, and spine) and 2 nonorthopaedic procedures (myringotomy, dental rehabilitation). Blood pressure was monitored with NIBP cuffs in 81 surgeries and intra-arterial catheters in 17 surgeries. Tourniquets (all applied to the lower extremity at a pneumatic pressure of 250 mm Hg) were used to minimize bleeding in 30 surgeries. There were no iatrogenic fractures associated with NIBP cuff use. One patient had a left humerus fracture that occurred during preoperative patient positioning. There were no fractures associated with tourniquet use and no complications related to intra-arterial catheters. In pediatric patients with OI, intraoperative use of NIBP cuffs and tourniquets was not associated with iatrogenic fracture. There were no complications related to intra-arterial catheter use. Care should be used during the perioperative period to prevent fractures during body positioning. Level IV.

  17. A novel splice site mutation in the dentin sialophosphoprotein gene in a Chinese family with dentinogenesis imperfecta type II

    International Nuclear Information System (INIS)

    Wang Haoyang; Hou Yanning; Cui Yingxia; Huang Yufeng; Shi Yichao; Xia Xinyi; Lu Hongyong; Wang Yunhua; Li Xiaojun

    2009-01-01

    Twenty-four individuals were investigated that spanned six generations in a Chinese family affected with an apparently autosomal dominant form of dentinogenesis imperfecta type II (DGI-II, OMIM 125490). All affected individuals presented with typical, clinical and radiographic features of DGI-II, but without bilateral progressive high-frequency sensorineural hearing loss. To investigate the mutated molecule, a positional candidate approach was used to determine the mutated gene in this family. Genomic DNA was obtained from 24 affected individuals, 18 unaffected relatives of the family and 50 controls. Haplotype analysis was performed using leukocyte DNA for 6 short tandem repeat (STR) markers present in chromosome 4 (D4S1534, GATA62A11, DSPP, DMP1, SPP1 and D4S1563). In the critical region between D4S1534 and DMP1, the dentin sialophosphoprotein (DSPP) gene (OMIM *125485) was considered as the strongest candidate gene. The first four exons and exon/intron boundaries of the gene were analyzed using DNA from 24 affected individuals and 18 unaffected relatives of the same family. DNA sequencing revealed a heterozygous deletion mutation in intron 2 (at positions -3 to -25), which resulted in a frameshift mutation, that changed the acceptor site sequence from CAG to AAG (IVS2-3C→A) and may also have disrupted the branch point consensus sequence in intron 2. The mutation was found in the 24 affected individuals, but not in the 18 unaffected relatives and 50 controls. The deletion was identified by allele-specific sequencing and denaturing high-performance liquid chromatography (DHPLC) analysis. We conclude that the heterozygous deletion mutation contributed to the pathogenesis of DGI-II

  18. Dentinogenesis imperfecta in adults with osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Gjørup, Hans; Hald, Jannie Dahl; Schmidt, Malene

    . In the evaluation of the dental hard tissues, signs of obliteration of pulp chambers, reduced length of roots, presence of pulp stones, taurodontism, and cervical constriction were assessed. Results: Among a total of 72 patients with OI, 20 (27.8 %) had DI. Obliteration and cervical constriction were frequently...... of Medical Endocrinology, Denmark. A clinical examination and a full-mouth periapical survey with digital intraoral radiographs using GX 1000 dental X-ray©, as well as a digital panoramic radiograph using the digital radiographic equipment Planmeca Promax© were performed. Patients had clinical photos taken...

  19. Involving Families with Osteogenesis Imperfecta in Health Service Research: Joint Development of the OI/ECE Questionnaire.

    Science.gov (United States)

    Dogba, Maman Joyce; Dahan-Oliel, Noémi; Snider, Laurie; Glorieux, Francis H; Durigova, Michaela; Palomo, Telma; Cordey, Michel; Bédard, Marie-Hélène; Bedos, Christophe; Rauch, Frank

    2016-01-01

    Despite the growing interest in understanding the psycho-social impact of rare genetic diseases, few studies examine this concept and even fewer seek to obtain feedback from families who have lived the experience. The aim of this project was to involve families of children living with osteogenesis imperfecta (OI) in the development of a tool to assess the impact of OI on the lives of patients and their families. This project used an integrated knowledge translation approach in which knowledge users (clinicians and people living with OI and their families) were consulted throughout the four steps of development, that is: content mapping, item generation, tool appraisal and pre-testing of the questionnaires. The International Classification of Functioning and Health was used as a framework for content mapping. Based on a scoping review we selected two validated tools to use as a basis for developing the questionnaire. The final parent self-report version measured six domains: experience of diagnosis; use of health services; use of social and psychological support services; expectations about tertiary specialized centers; and socio-demographic information. A total of 27 out of 40 families receiving care at the Shriners Hospital for Children-Canada and invited to participate in the pre-test returned the completed questionnaires. In more than two-thirds of families (69%; n = 18) OI was suspected either at or within the first 3 months after birth. Up to 46% of families consulted between 3 and 5 doctors (46%; n = 12) prior to final diagnosis. The use of services by families varied from 0 to 16 consultations, 0 to 9 exploratory examinations and 1 to 10 types of allied health services. In the 12 months prior to the study, fewer than a quarter of children had been admitted, for treatment, for hospital stays of longer than 8 hours or to an emergency department (24% and 9% respectively). Only 29% of parents received psychological support. This joint development process

  20. Involving Families with Osteogenesis Imperfecta in Health Service Research: Joint Development of the OI/ECE Questionnaire.

    Directory of Open Access Journals (Sweden)

    Maman Joyce Dogba

    Full Text Available Despite the growing interest in understanding the psycho-social impact of rare genetic diseases, few studies examine this concept and even fewer seek to obtain feedback from families who have lived the experience. The aim of this project was to involve families of children living with osteogenesis imperfecta (OI in the development of a tool to assess the impact of OI on the lives of patients and their families.This project used an integrated knowledge translation approach in which knowledge users (clinicians and people living with OI and their families were consulted throughout the four steps of development, that is: content mapping, item generation, tool appraisal and pre-testing of the questionnaires. The International Classification of Functioning and Health was used as a framework for content mapping. Based on a scoping review we selected two validated tools to use as a basis for developing the questionnaire. The final parent self-report version measured six domains: experience of diagnosis; use of health services; use of social and psychological support services; expectations about tertiary specialized centers; and socio-demographic information.A total of 27 out of 40 families receiving care at the Shriners Hospital for Children-Canada and invited to participate in the pre-test returned the completed questionnaires. In more than two-thirds of families (69%; n = 18 OI was suspected either at or within the first 3 months after birth. Up to 46% of families consulted between 3 and 5 doctors (46%; n = 12 prior to final diagnosis. The use of services by families varied from 0 to 16 consultations, 0 to 9 exploratory examinations and 1 to 10 types of allied health services. In the 12 months prior to the study, fewer than a quarter of children had been admitted, for treatment, for hospital stays of longer than 8 hours or to an emergency department (24% and 9% respectively. Only 29% of parents received psychological support.This joint development

  1. BPS804 Anti-Sclerostin Antibody in Adults With Moderate Osteogenesis Imperfecta: Results of a Randomized Phase 2a Trial.

    Science.gov (United States)

    Glorieux, Francis H; Devogelaer, Jean-Pierre; Durigova, Michaela; Goemaere, Stefan; Hemsley, Sarah; Jakob, Franz; Junker, Uwe; Ruckle, Jon; Seefried, Lothar; Winkle, Peter J

    2017-07-01

    This 21-week, open-label, phase 2a trial aimed to evaluate the pharmacodynamics and safety of multiple, escalating infusions of BPS804, a neutralizing, anti-sclerostin antibody, in adults with moderate osteogenesis imperfecta (OI). Patients received BPS804 (three escalating doses each separated by 2 weeks [5, 10, and 20 mg/kg]) or no treatment (reference group). The primary efficacy endpoints were mean changes from baseline to day 43 in: procollagen type 1 N-terminal propeptide (P1NP), procollagen type 1 C-terminal propeptide (P1CP), bone-specific alkaline phosphatase (BSAP), osteocalcin (OC), and type 1 collagen cross-linked C-telopeptide (CTX-1). Mean change from baseline to day 141 in lumbar spine areal bone mineral density (aBMD) was also assessed. BPS804 safety and tolerability were assessed every 2 weeks. Overall, 14 adults were enrolled (BPS804 group: n = 9, mean age 30.7 years, mean aBMD Z-score -2.6; reference group, n = 5, mean age 27.4 years, mean aBMD Z-score -2.2). In the BPS804 group, P1NP, P1CP, BSAP, and OC were increased by 84% (p < 0.001), 53% (p = 0.003), 59% (p < 0.001), and 44% (p = 0.012), respectively, versus baseline (reference: P1NP, +6% [p = 0.651]; P1CP, +5% [p = 0.600]; BSAP, -13% [p = 0.582]; OC, -19% [p = 0.436]). BPS804 treatment downregulated CTX-1 by 44% from baseline (reference: -7%; significance was not tested for this biomarker), and increased aBMD by 4% (p = 0.038; reference group: +1%; p = 0.138). BPS804 was generally well tolerated. There were 32 adverse events reported in nine patients; none was suspected to be treatment-related. There were no treatment-related fractures. BPS804 stimulates bone formation, reduces bone resorption, and increases lumbar spine aBMD in adults with moderate OI. This paves the way for a longer-term, phase 3 trial into the efficacy, safety, and tolerability of BPS804 in patients with OI. © 2017 American Society for Bone and Mineral Research. © 2017

  2. Bone structure assessed by HR-pQCT, TBS and DXL in adult patients with different types of osteogenesis imperfecta.

    Science.gov (United States)

    Kocijan, R; Muschitz, C; Haschka, J; Hans, D; Nia, A; Geroldinger, A; Ardelt, M; Wakolbinger, R; Resch, H

    2015-10-01

    Bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) was assessed in adult patients with mild, moderate, and severe osteogenesis imperfecta (OI). The trabecular bone score (TBS), bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), and dual X-ray and laser (DXL) at the calcaneus were likewise assessed in patients with OI. Trabecular microstructure and BMD in particular were severely altered in patients with OI. OI is characterized by high fracture risk but not necessarily by low BMD. The main purpose of this study was to assess bone microarchitecture and BMD at different skeletal sites in different types of OI. HR-pQCT was performed in 30 patients with OI (mild OI-I, n = 18 (41.8 [34.7, 55.7] years) and moderate to severe OI-III-IV, n = 12 (47.6 [35.3, 58.4] years)) and 30 healthy age-matched controls. TBS, BMD by DXA at the lumbar spine and hip, as well as BMD by DXL at the calcaneus were likewise assessed in patients with OI only. At the radius, significantly lower trabecular parameters including BV/TV (p = 0.01 and p < 0.0001, respectively) and trabecular number (p < 0.0001 and p < 0.0001, respectively) as well as an increased inhomogeneity of the trabecular network (p < 0.0001 and p < 0.0001, respectively) were observed in OI-I and OI-III-IV in comparison to the control group. Similar results for trabecular parameters were found at the tibia. Microstructural parameters were worse in OI-III-IV than in OI-I. No significant differences were found in cortical thickness and cortical porosity between the three subgroups at the radius. The cortical thickness of the tibia was thinner in OI-I (p < 0.001), but not OI-III-IV, when compared to controls. Trabecular BMD and trabecular bone microstructure in particular are severely altered in patients with clinical OI-I and OI-III-IV. Low TBS and DXL and their significant associations to HR-pQCT parameters of trabecular bone support this conclusion.

  3. The influence of ibandronate treatment on bone density and biochemical bone markers in patients with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Ingmar Ipach

    2012-09-01

    Full Text Available Osteogenesis imperfecta (OI is characterized by different signs including increased bone fragility, short stature, blue sclera, abnormal tooth growth and often secondary immobility. No curative therapy has been found for this rare disease up to now, and different pharmacological substances have been tried as treatment for severe forms of OI. Promising results were seen with intravenous bisphosphonates in the treatment of patients with OI. The aim of present study was to show the effect of intravenous ibandronate therapy on bone density and bone metabolism markers. We analyzed the data of 27 patients with the diagnosis of OI who were treated off-label with intravenous ibandronate. Ibandronate was administered by intravenous infusion every three months at a dosage of 0.3-2 mg. Bone turnover markers and bone density were measured before starting therapy and every three months during treatment. Bone density was measured by using an ultrasound imaging system providing an accurate image of the calcaneus and by evaluating broadband ultrasound attenuation (BUA. Twenty-seven patients were treated with intravenous iban- dronate during the observation period. 18 were female. The mean age of all patients was 23.9 years ± 19.6 (range 4-63. Seventeen patients were categorized to have OI Type I, 5 patients to have OI Type III and 5 patients to have OI Type IV. There was a statistically significant decrease in total alkaline phosphatase (P<0.0001. We detected also a statistically significant decrease in the ratio urinary deoxypyridinoline/urinary creatinine (P=0.0048 and the ratio urinary pyridinoline/urinary creatinine (P<0.0001 respectively. There was also a statistically significant increase in serum magnesium (P=0.034 and BUA (P=0.0071. No statistically significant changes were seen for total serum calcium (P=0.16, the ratio of urine calcium/urine creatinine (P=0.29, alkaline phosphatase (isoform bone (P=0.3, procollagen-I-peptide (P=0.5, osteocalcin (P=0

  4. Pain and quality of life of children and adolescents with osteogenesis imperfecta over a bisphosphonate treatment cycle.

    Science.gov (United States)

    Tsimicalis, Argerie; Boitor, Madalina; Ferland, Catherine E; Rauch, Frank; Le May, Sylvie; Carrier, Jaimie Isabel; Ngheim, Tracy; Bilodeau, Claudette

    2018-04-11

    The objective was to describe the pain and quality of life among children and adolescents with any osteogenesis imperfecta (OI) type over one intravenous bisphosphonate treatment cycle from a child and parental perspective. A prospective, observational study was conducted, where children and adolescents evaluated their pain intensity, location, and quality, as well as quality of life before, 1 week after treatment, and 6 months later. Quality of life was also evaluated from the parental perspective at the same three time points. Thirty-three child/parent dyads participated. The results showed that pain intensity on the 0-10 self-report scale after the Zoledronate infusion (median = 0, range = 0-6) was not different from pre (median = 2, range = 0-10) and 6-months post-scores (median = 2, range = 0-8) (p = 0.170). Children and adolescents with OI reported experiencing pain mainly in the ankles and the anterior and posterior shoulders. They selected evaluative pain descriptors such as uncomfortable (n = 16, 48%) and annoying (n = 13, 39%). Children and adolescents' functioning and quality of life did not change significantly across the bisphosphonate treatment cycle (p = 0.326), parents perceived an improvement immediately after the treatment compared to before (p = 0.016). Children and adolescents with OI experience mild, yet complex pain localized across several body areas. There is little fluctuation in the pain intensity and functioning of children with OI undergoing bisphosphonate treatment. What is Known: • Acute and chronic musculoskeletal pain remains a major issue in OI. • Pain has a negative impact on quality of life. What is New: • New and unpublished methods and findings describing the pain and quality of life of children and adolescents with OI over one intravenous bisphosphonate treatment cycle from a child- and parental-proxy perspective. • Children and adolescents with OI experience pain intensity that is mild, yet

  5. Complicações hemorrágicas intracranianas na osteogênese imperfeita Intracranial hemorrhagic complications in cases of osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Laertel F. Fassoni

    1968-09-01

    Full Text Available São descritas complicações hemorrágicas intracranianas em dois pacientes com osteogênese imperfeita. Sangramento espontâneo ocorreu no espaço subaracnóideo em um dos pacientes e no espaço subdural, no outro. Os achados clínicos e paraclínicos são discutidos à luz de um distrbio mesenquimatoso difuso semelhante ao que caracteriza as demais moléstias hereditárias do mesênquima.The intracranial hemorrhagic complications in two patients with osteogenesis imperfecta are described. Spontaneous bleeding into the subarachnoid space occurred in one patient and into the subdural space in another. The clinical findings and their relationship to a generalized disturbance of mesenchymal tissue are discussed.

  6. Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive osteogenesis imperfecta.

    Science.gov (United States)

    Christiansen, Helena E; Schwarze, Ulrike; Pyott, Shawna M; AlSwaid, Abdulrahman; Al Balwi, Mohammed; Alrasheed, Shatha; Pepin, Melanie G; Weis, Mary Ann; Eyre, David R; Byers, Peter H

    2010-03-12

    Osteogenesis imperfecta (OI) is characterized by bone fragility and fractures that may be accompanied by bone deformity, dentinogenesis imperfecta, short stature, and shortened life span. About 90% of individuals with OI have dominant mutations in the type I collagen genes COL1A1 and COL1A2. Recessive forms of OI resulting from mutations in collagen-modifying enzymes and chaperones CRTAP, LEPRE1, PPIB, and FKBP10 have recently been identified. We have identified an autosomal-recessive missense mutation (c.233T>C, p.Leu78Pro) in SERPINH1, which encodes the collagen chaperone-like protein HSP47, that leads to a severe OI phenotype. The mutation results in degradation of the endoplasmic reticulum resident HSP47 via the proteasome. Type I procollagen accumulates in the Golgi of fibroblasts from the affected individual and a population of the secreted type I procollagen is protease sensitive. These findings suggest that HSP47 monitors the integrity of the triple helix of type I procollagen at the ER/cis-Golgi boundary and, when absent, the rate of transit from the ER to the Golgi is increased and helical structure is compromised. The normal 3-hydroxylation of the prolyl residue at position 986 of the triple helical domain of proalpha1(I) chains places the role of HSP47 downstream from the CRTAP/P3H1/CyPB complex that is involved in prolyl 3-hydroxylation. Identification of this mutation in SERPINH1 gives further insight into critical steps of the collagen biosynthetic pathway and the molecular pathogenesis of OI. Copyright 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  7. Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents with osteogenesis imperfecta - A retrospective cohort study.

    Directory of Open Access Journals (Sweden)

    Kristofer Andersson

    Full Text Available Osteogenesis imperfecta (OI is a heterogeneous group of disorders of connective tissue, caused mainly by mutations in the collagen I genes (COL1A1 and COL1A2. Dentinogenesis imperfecta (DGI and other dental aberrations are common features of OI. We investigated the association between collagen I mutations and DGI, taurodontism, and retention of permanent second molars in a retrospective cohort of 152 unrelated children and adolescents with OI. The clinical examination included radiographic evaluations. Teeth from 81 individuals were available for histopathological evaluation. COL1A1/2 mutations were found in 104 individuals by nucleotide sequencing. DGI was diagnosed clinically and radiographically in 29% of the individuals (44/152 and through isolated histological findings in another 19% (29/152. In the individuals with a COL1A1 mutation, 70% (7/10 of those with a glycine substitution located C-terminal of p.Gly305 exhibited DGI in both dentitions while no individual (0/7 with a mutation N-terminal of this point exhibited DGI in either dentition (p = 0.01. In the individuals with a COL1A2 mutation, 80% (8/10 of those with a glycine substitution located C terminal of p.Gly211 exhibited DGI in both dentitions while no individual (0/5 with a mutation N-terminal of this point (p = 0.007 exhibited DGI in either dentition. DGI was restricted to the deciduous dentition in 20 individuals. Seventeen had missense mutations where glycine to serine was the most prevalent substitution (53%. Taurodontism occurred in 18% and retention of permanent second molars in 31% of the adolescents. Dental aberrations are strongly associated with qualitatively changed collagen I. The varying expressivity of DGI is related to the location of the collagen I mutation. Genotype information may be helpful in identifying individuals with OI who have an increased risk of dental aberrations.

  8. Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents with osteogenesis imperfecta – A retrospective cohort study

    Science.gov (United States)

    Dahllöf, Göran; Lindahl, Katarina; Kindmark, Andreas; Grigelioniene, Giedre; Åström, Eva; Malmgren, Barbro

    2017-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, caused mainly by mutations in the collagen I genes (COL1A1 and COL1A2). Dentinogenesis imperfecta (DGI) and other dental aberrations are common features of OI. We investigated the association between collagen I mutations and DGI, taurodontism, and retention of permanent second molars in a retrospective cohort of 152 unrelated children and adolescents with OI. The clinical examination included radiographic evaluations. Teeth from 81 individuals were available for histopathological evaluation. COL1A1/2 mutations were found in 104 individuals by nucleotide sequencing. DGI was diagnosed clinically and radiographically in 29% of the individuals (44/152) and through isolated histological findings in another 19% (29/152). In the individuals with a COL1A1 mutation, 70% (7/10) of those with a glycine substitution located C-terminal of p.Gly305 exhibited DGI in both dentitions while no individual (0/7) with a mutation N-terminal of this point exhibited DGI in either dentition (p = 0.01). In the individuals with a COL1A2 mutation, 80% (8/10) of those with a glycine substitution located C terminal of p.Gly211 exhibited DGI in both dentitions while no individual (0/5) with a mutation N-terminal of this point (p = 0.007) exhibited DGI in either dentition. DGI was restricted to the deciduous dentition in 20 individuals. Seventeen had missense mutations where glycine to serine was the most prevalent substitution (53%). Taurodontism occurred in 18% and retention of permanent second molars in 31% of the adolescents. Dental aberrations are strongly associated with qualitatively changed collagen I. The varying expressivity of DGI is related to the location of the collagen I mutation. Genotype information may be helpful in identifying individuals with OI who have an increased risk of dental aberrations. PMID:28498836

  9. Application of 3-Dimensional Printing in a Case of Osteogenesis Imperfecta for Patient Education, Anatomic Understanding, Preoperative Planning, and Intraoperative Evaluation.

    Science.gov (United States)

    Eisenmenger, Laura B; Wiggins, Richard H; Fults, Daniel W; Huo, Eugene J

    2017-11-01

    The techniques and applications of 3-dimensional (3D) printing have progressed at a fast pace. In the last 10 years, there has been significant progress in applying this technology to medical applications. We present a case of osteogenesis imperfecta in which treatment was aided by prospectively using patient-specific, anatomically accurate 3D prints of the calvaria. The patient-specific, anatomically accurate 3D prints were used in the clinic and in the operating room to augment patient education, improve surgical decision making, and enhance preoperative planning. A 41-year-old woman with osteogenesis imperfecta and an extensive neurosurgical history presented for cranioplasty revision. Computed tomography (CT) data obtained as part of routine preoperative imaging were processed into a 3D model. The 3D patient-specific models were used in the clinic for patient education and in the operating room for preoperative visualization, planning, and intraoperative evaluation of anatomy. The patient reported the 3D models improved her understanding and comfort with the planned surgery when compared with discussing the procedure with the neurosurgeon or viewing the CT images with a neuroradiologist. The neurosurgeon reported an improved understanding of the patient's anatomy and potential cause of patient symptoms as well as improved preoperative planning compared with viewing the CT imaging alone. The neurosurgeon also reported an improvement in the planned surgical approach with a better intraoperative visualization and confirmation of the regions of planned calvarial resection. The use of patient-specific, anatomically accurate 3D prints may improve patient education, surgeon understanding and visualization, preoperative decision making, and intraoperative management. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Microscopic study of dental hard tissues in primary teeth with Dentinogenesis Imperfecta Type II: Correlation of 3D imaging using X-ray microtomography and polarising microscopy.

    Science.gov (United States)

    Davis, Graham R; Fearne, Janice M; Sabel, Nina; Norén, Jörgen G

    2015-07-01

    The aim of this study was to examine the histological appearance of dental hard tissues in primary teeth from children with DI using conventional polarised light microscopy and correlate that with 3D imaging using X-ray microtomograpy (XMT) to gain a further understanding of the dentine structure of teeth diagnosed with dentinogenesis imperfecta. Undecalcified sections of primary teeth from patients diagnosed with Dentinogenesis Imperfecta Type II were examined using polarised light microscopy. XMT was employed for 3D-imaging and analysis of the dentine. The polarised light microscopy and XMT revealed tubular structures in the dentine seen as vacuoles coinciding with the path of normal dentinal tubules but not continuous tubules. The size of the tubules was close to that of capillaries. The largest tubular structures had a direction corresponding to where the pulp tissue would have been located during primary dentine formation. The dysfunctional mineralisation of the dentine and obliteration of the pulp evidently leaves blood vessels in the dentine which have in the main been tied off and, in the undecalcified sections, appear as vacuoles. Although from radiographs, the pulp in teeth affected by Dentinogenesis Imperfect type II appears to be completely obliterated, a network of interconnected vessels may remain. The presence of large dentinal tubules and blood vessels, or the remnants of blood vessels, could provide a pathway for bacteria from the oral cavity. This might account for why some of these teeth develop periapical abscesses in spite of apparently having no pulp. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents with osteogenesis imperfecta - A retrospective cohort study.

    Science.gov (United States)

    Andersson, Kristofer; Dahllöf, Göran; Lindahl, Katarina; Kindmark, Andreas; Grigelioniene, Giedre; Åström, Eva; Malmgren, Barbro

    2017-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, caused mainly by mutations in the collagen I genes (COL1A1 and COL1A2). Dentinogenesis imperfecta (DGI) and other dental aberrations are common features of OI. We investigated the association between collagen I mutations and DGI, taurodontism, and retention of permanent second molars in a retrospective cohort of 152 unrelated children and adolescents with OI. The clinical examination included radiographic evaluations. Teeth from 81 individuals were available for histopathological evaluation. COL1A1/2 mutations were found in 104 individuals by nucleotide sequencing. DGI was diagnosed clinically and radiographically in 29% of the individuals (44/152) and through isolated histological findings in another 19% (29/152). In the individuals with a COL1A1 mutation, 70% (7/10) of those with a glycine substitution located C-terminal of p.Gly305 exhibited DGI in both dentitions while no individual (0/7) with a mutation N-terminal of this point exhibited DGI in either dentition (p = 0.01). In the individuals with a COL1A2 mutation, 80% (8/10) of those with a glycine substitution located C terminal of p.Gly211 exhibited DGI in both dentitions while no individual (0/5) with a mutation N-terminal of this point (p = 0.007) exhibited DGI in either dentition. DGI was restricted to the deciduous dentition in 20 individuals. Seventeen had missense mutations where glycine to serine was the most prevalent substitution (53%). Taurodontism occurred in 18% and retention of permanent second molars in 31% of the adolescents. Dental aberrations are strongly associated with qualitatively changed collagen I. The varying expressivity of DGI is related to the location of the collagen I mutation. Genotype information may be helpful in identifying individuals with OI who have an increased risk of dental aberrations.

  12. Tratamento cirúrgico das deformidades e fraturas em membros inferiores na osteogênese imperfeita Surgical treatment of deformities and fractures on lower limbs with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Marcelo de Toledo Piza Watzl

    2009-01-01

    Full Text Available OBJETIVO: Fazer uma revisão dos pacientes portadores de Osteogênese Imperfeita avaliando o tratamento cirúrgico das fraturas e deformidades nos membros inferiores para determinar a eficiência da técnica utilizando as hastes fixas (não-extensíveis. CASUÍSTICA E MÉTODO: Foram revisados os prontuários, radiografias pré-operatórias e pós-operatórias de todos os pacientes portadores de Osteogênese Imperfeita que foram tratados no Alfred I duPont Institute (EUA entre 1965 e 1999. RESULTADOS: Quatorze pacientes (cinco meninos e nove meninas foram submetidos às hastes fixas nos membros inferiores com um total de 37 procedimentos realizados. CONCLUSÃO: O procedimento de fixação intramedular com hastes não extensíveis mostrou ser um método de baixa morbidade, capaz de manter e até mesmo de melhorar o status de deambulador destes pacientes.OBJECTIVE: To provide a review of patients with Osteogenesis Imperfecta by analyzing the deformities, fractures and results of surgical treatment on lower limbs in order to determine the efficiency of the use of non-elongating rods (non extensible. MATERIALS AND METHOD: Medical records, preoperative and postoperative X-ray images of all the patients who had imperfect osteogenesis and treated at the Alfred I duPont Institute (USA between 1965 and 1999 have been reviewed. RESULTS: Fourteen patients (five boys and nine girls were submitted to the non-elongating rods on their lower limbs, totaling 37 procedures. CONCLUSION: The procedure of intramedullary fixation with non-elongating rods to treat fractures and deformities on lower limb in Osteogenesis Imperfecta was proven to be a low morbidity method without interfering with the ambulatory status of these patients.

  13. Diplopia due to Dacryops

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    Rahmi Duman

    2013-01-01

    Full Text Available Dacryops is a lacrimal ductal cyst. It is known that it can cause globe displacement, motility restriction, and proptosis because of the mass effect. Diplopia due to dacryops has not been reported previously. Here, we present a 57-year-old man with binocular horizontal diplopia that occurred during left direction gaze due to dacryops.

  14. Bone mineral properties in growing Col1a2(+/G610C) mice, an animal model of osteogenesis imperfecta.

    Science.gov (United States)

    Masci, Marco; Wang, Min; Imbert, Laurianne; Barnes, Aileen M; Spevak, Lyudmila; Lukashova, Lyudmila; Huang, Yihe; Ma, Yan; Marini, Joan C; Jacobsen, Christina M; Warman, Matthew L; Boskey, Adele L

    2016-06-01

    The Col1a2(+/G610C) knock-in mouse, models osteogenesis imperfecta in a large old order Amish family (OOA) with type IV OI, caused by a G-to-T transversion at nucleotide 2098, which alters the gly-610 codon in the triple-helical domain of the α2(I) chain of type I collagen. Mineral and matrix properties of the long bones and vertebrae of male Col1a2(+/G610C) and their wild-type controls (Col1a2(+/+)), were characterized to gain insight into the role of α2-chain collagen mutations in mineralization. Additionally, we examined the rescuability of the composition by sclerostin inhibition initiated by crossing Col1a2(+/G610C) with an LRP(+/A214V) high bone mass allele. At age 10-days, vertebrae and tibia showed few alterations by micro-CT or Fourier transform infrared imaging (FTIRI). At 2-months-of-age, Col1a2(+/G610C) tibias had 13% fewer secondary trabeculae than Col1a2(+/+), these were thinner (11%) and more widely spaced (20%) than those of Col1a2(+/+) mice. Vertebrae of Col1a2(+/G610C) mice at 2-months also had lower bone volume fraction (38%), trabecular number (13%), thickness (13%) and connectivity density (32%) compared to Col1(a2+/+). The cortical bone of Col1a2(+/G610C) tibias at 2-months had 3% higher tissue mineral density compared to Col1a2(+/+); Col1a2(+/G610C) vertebrae had lower cortical thickness (29%), bone area (37%) and polar moment of inertia (38%) relative to Col1a2(+/+). FTIRI analysis, which provides information on bone chemical composition at ~7μm-spatial resolution, showed tibias at 10-days did not differ between genotypes. Comparing identical bone types in Col1a2(+/G610C) to Col1a2(+/+) at 2-months-of-age, tibias showed higher mineral-to-matrix ratio in trabeculae (17%) and cortices (31%). and in vertebral cortices (28%). Collagen maturity was 42% higher at 10-days-of-age in Col1a2(+/G610C) vertebral trabeculae and in 2-month tibial cortices (12%), vertebral trabeculae (42%) and vertebral cortices (12%). Higher acid-phosphate substitution

  15. Diagnóstico pré-natal e parto transpelviano na osteogênese imperfeita: relato de caso Prenatal diagnosis and vaginal delivery in osteogenesis imperfecta: a case report

    Directory of Open Access Journals (Sweden)

    Alex Sandro Rolland de Souza

    2006-04-01

    Full Text Available A osteogênese imperfeita é doença do tecido conjuntivo devida a anormalidades quantitativas ou qualitativas do colágeno tipo I, transmitida geneticamente, por gene autossômico dominante ou recessivo, que determina fragilidade óssea. Relata-se o caso clínico de paciente de 19 anos, primigesta, encaminhada ao setor de medicina fetal com ultra-sonografia pregressa evidenciando encurtamento de extremidades fetais. Na avaliação morfológica, identificou-se contorno craniano irregular com deformidade à compressão do pólo cefálico, membros com rizo e mesomelia, rarefação óssea e encurvamento de ossos longos (fraturas. A paciente evoluiu com parto transpelviano na 35ª semana de gestação. O recém-nascido apresentou Apgar de 6 no 1ª minuto e 8 no 5ª minuto, sexo masculino, pesando 1.990 gramas. Observado crânio irregular, ossificação diminuída, esclera azulada e fraturas consolidadas com deformidades em todos os membros. O recém-nascido apresentou boa evolução neonatal, recebendo alta hospitalar em boas condições. O diagnóstico pré-natal é de grande importância para adequado acompanhamento da gravidez e a via de parto transpelviana não ocasionou piora do prognóstico neonatal, pois não foram diagnosticadas fraturas recentes.Osteogenesis imperfecta is a connective tissue disorder due to quantitative and qualitative anomalies in type 1 collagen, genetically transmitted by a dominant or recessive autosomal gene, leading to bone fragility. We report a case of a 19-year-old G1 PO patient referred to our institution following a screening ultrasound that demonstrated short limb fetal extremities. A level 3 scan was performed which evidenced an irregular cranial shape and compression of the cephalic pole with moderate transducer pressure. Limb shortening, decreased echoes and fractures of long bones were found on our scan evaluation. A vaginal delivery occurred at 35 weeks of gestation. The male newborn, weighing 1.990 grams

  16. Due process traditionalism.

    Science.gov (United States)

    Sunstein, Cass R

    2008-06-01

    In important cases, the Supreme Court has limited the scope of "substantive due process" by reference to tradition, but it has yet to explain why it has done so. Due process traditionalism might be defended in several distinctive ways. The most ambitious defense draws on a set of ideas associated with Edmund Burke and Friedrich Hayek, who suggested that traditions have special credentials by virtue of their acceptance by many minds. But this defense runs into three problems. Those who have participated in a tradition may not have accepted any relevant proposition; they might suffer from a systematic bias; and they might have joined a cascade. An alternative defense sees due process traditionalism as a second-best substitute for two preferable alternatives: a purely procedural approach to the Due Process Clause, and an approach that gives legislatures the benefit of every reasonable doubt. But it is not clear that in these domains, the first-best approaches are especially attractive; and even if they are, the second-best may be an unacceptably crude substitute. The most plausible defense of due process traditionalism operates on rule-consequentialist grounds, with the suggestion that even if traditions are not great, they are often good, and judges do best if they defer to traditions rather than attempting to specify the content of "liberty" on their own. But the rule-consequentialist defense depends on controversial and probably false assumptions about the likely goodness of traditions and the institutional incapacities of judges.

  17. What Is Osteogenesis Imperfecta?

    Science.gov (United States)

    ... Site Map Accessibility Privacy FOIA Disclaimer Glossary FAQs Digital Strategy Open Source Data Public Data Listing Download Adobe Reader Disclaimer Glossary FAQs Digital Strategy Open Source Data Public Data Listing Download Adobe ...

  18. Osteogenesis Imperfecta Overview

    Science.gov (United States)

    ... muscle strength. Care of fractures, extensive surgical and dental procedures, and physical therapy are often recommended for people with OI. Use of wheelchairs, braces, and other mobility aids is common, particularly ( ...

  19. Role of genes in oro-dental diseases

    Directory of Open Access Journals (Sweden)

    Kavitha B

    2010-01-01

    Full Text Available In oral cavity, the spectrum of diseases due to genetic alterations ranges from developmental disturbances of teeth to the pre-cancerous and cancerous lesions. Of late, significant progress has been made in the molecular analysis of tumors. With molecular genetic testing emerging as diagnostic, prognostic, and therapeutic approach, a review of genetic alterations ranging from the development of oro-facial structures to the tumors in the head and neck region are addressed in this article. The functional regulatory aspect of genes in relation to oro-facial structures are discussed separately, i.e., in relation to tooth genesis, tooth agenesis (non-syndromic, syndromic, tooth structural alterations, syndromic oro-facial defects, bone diseases, skin diseases (genodermatoses, and malignant tumors. In this literature, various genes involved in the development of the oro-facial structures and tooth in particular are discussed. The genetic basis of disorders in the tooth development (agenesis, hypodontia, tooth structural defects like amelogenesis imperfecta (AI, dentinogenesis imperfecta (DI, and oro-facial structural alterations (various syndromes are explained.

  20. Eczematous dermatitis due to subcutaneous teriparatide injection.

    Science.gov (United States)

    Chu, Howard; Kim, Dae Suk

    2016-05-01

    Teriparatide, or recombinant human parathyroid hormone, is approved for the treatment of osteoporosis. Possible cutaneous adverse events of teriparatide are urticaria, injection site pain, swelling, bruising, and pruritus. However, there have been no reports of widespread eczematous reactions caused by teriparatide. A 47-year-old male was recently diagnosed with osteogenesis imperfecta and prior to teeth extractions, he was subcutaneously injected with teriparatide. The patient developed multiple pruritic erythematous papules and plaques on his abdomen, around the site of the injection. A skin biopsy was done, which showed mild spongiosis and superficial perivenular lymphocytic infiltration with a few eosinophils. Drug-related eczematous changes were most likely suspected and in addition to the discontinuation of the injection, topical steroid was prescribed, in which dramatic improvements were observed. We report the eczematous hypersensitivity reaction caused by teriparatide, which is an adverse reaction that has not been reported before.

  1. Human due diligence.

    Science.gov (United States)

    Harding, David; Rouse, Ted

    2007-04-01

    Most companies do a thorough job of financial due diligence when they acquire other companies. But all too often, deal makers simply ignore or underestimate the significance of people issues in mergers and acquisitions. The consequences are severe. Most obviously, there's a high degree of talent loss after a deal's announcement. To make matters worse, differences in decision-making styles lead to infighting; integration stalls; and productivity declines. The good news is that human due diligence can help companies avoid these problems. Done early enough, it helps acquirers decide whether to embrace or kill a deal and determine the price they are willing to pay. It also lays the groundwork for smooth integration. When acquirers have done their homework, they can uncover capability gaps, points of friction, and differences in decision making. Even more important, they can make the critical "people" decisions-who stays, who goes, who runs the combined business, what to do with the rank and file-at the time the deal is announced or shortly thereafter. Making such decisions within the first 30 days is critical to the success of a deal. Hostile situations clearly make things more difficult, but companies can and must still do a certain amount of human due diligence to reduce the inevitable fallout from the acquisition process and smooth the integration. This article details the steps involved in conducting human due diligence. The approach is structured around answering five basic questions: Who is the cultural acquirer? What kind of organization do you want? Will the two cultures mesh? Who are the people you most want to retain? And how will rank-and-file employees react to the deal? Unless an acquiring company has answered these questions to its satisfaction, the acquisition it is making will be very likely to end badly.

  2. Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α.

    Science.gov (United States)

    Brunetti, G; Papadia, F; Tummolo, A; Fischetto, R; Nicastro, F; Piacente, L; Ventura, A; Mori, G; Oranger, A; Gigante, I; Colucci, S; Ciccarelli, M; Grano, M; Cavallo, L; Delvecchio, M; Faienza, M F

    2016-07-01

    In this study, we investigated the bone cell activity in patients with osteogenesis imperfecta (OI) treated and untreated with neridronate. We demonstrated the key role of Dickkopf-1 (DKK1), receptor activator of nuclear factor-κB ligand (RANKL), and tumor necrosis factor alpha (TNF-α) in regulating bone cell of untreated and treated OI subjects. These cytokines could represent new pharmacological targets for OI. Bisphosphonates are widely used in the treatment of children with osteogenesis imperfecta (OI) with the objective of reducing the risk of fractures. Although bisphosphonates increase bone mineral density in OI subjects, the effects on fracture incidence are conflicting. The aim of this study was to investigate the mechanisms underlying bone cell activity in subjects with mild untreated forms of OI and in a group of subjects with severe OI treated with cycles of intravenous neridronate. Sclerostin, DKK1, TNF-α, RANKL, osteoprotegerin (OPG), and bone turnover markers were quantified in serum of 18 OI patients (12 females, mean age 8.86 ± 3.90), 8 of which were receiving cyclic intravenous neridronate, and 21 sex- and age-matched controls. The effects on osteoblastogenesis and OPG expression of media conditioned by the serum of OI patients and anti-DKK1 neutralizing antibody were evaluated. Osteoclastogenesis was assessed in cultures from patients and controls. DKK1 and RANKL levels were significantly increased both in untreated and in treated OI subjects with respect to controls. The serum from patients with high DKK1 levels inhibited both osteoblast differentiation and OPG expression in vitro. High RANKL and low OPG messenger RNA (mRNA) levels were found in lymphomonocytes from patients. High amounts of TNF-α were expressed by monocytes, and an elevated percentage of circulating CD11b-CD51/CD61+ osteoclast precursors was observed in patients. Our study demonstrated the key role of DKK1, RANKL, and TNF-α in regulating bone cell activity of subjects

  3. Upregulating CXCR4 in human fetal mesenchymal stem cells enhances engraftment and bone mechanics in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Jones, Gemma N; Moschidou, Dafni; Lay, Kenneth; Abdulrazzak, Hassan; Vanleene, Maximilien; Shefelbine, Sandra J; Polak, Julia; de Coppi, Paolo; Fisk, Nicholas M; Guillot, Pascale V

    2012-01-01

    Stem cells have considerable potential to repair damaged organs and tissues. We previously showed that prenatal transplantation of human first trimester fetal blood mesenchymal stem cells (hfMSCs) in a mouse model of osteogenesis imperfecta (oim mice) led to a phenotypic improvement, with a marked decrease in fracture rate. Donor cells differentiated into mature osteoblasts, producing bone proteins and minerals, including collagen type Iα2, which is absent in nontransplanted mice. This led to modifications of the bone matrix and subsequent decrease of bone brittleness, indicating that grafted cells directly contribute to improvement of bone mechanical properties. Nevertheless, the therapeutic effect was incomplete, attributing to the limited level of engraftment in bone. In this study, we show that although migration of hfMSCs to bone and bone marrow is CXCR4-SDF1 (SDF1 is stromal-derived factor) dependent, only a small number of cells present CXCR4 on the cell surface despite high levels of internal CXCR4. Priming with SDF1, however, upregulates CXCR4 to increase the CXCR4(+) cell fraction, improving chemotaxis in vitro and enhancing engraftment in vivo at least threefold in both oim and wild-type bone and bone marrow. Higher engraftment in oim bones was associated with decreased bone brittleness. This strategy represents a step to improve the therapeutic benefits of fetal cell therapy toward being curative.

  4. Confirmation of the pathogenicity of a mutation p.G337C in the COL1A2 gene associated with osteogenesis imperfecta

    Science.gov (United States)

    Jia, Mingrui; Shi, Ranran; Zhao, Xuli; Fu, Zhijian; Bai, Zhijing; Sun, Tao; Zhao, Xuejun; Wang, Wenbo; Xu, Chao; Yan, Fang

    2017-01-01

    Abstract Mutation analysis as the gold standard is particularly important in diagnosis of osteogenesis imperfecta (OI) and it may be preventable upon early diagnosis. In this study, we aimed to analyze the clinical and genetic materials of an OI pedigree as well as to confirm the deleterious property of the mutation. A pedigree with OI was identified. All family members received careful clinical examinations and blood was drawn for genetic analyses. Genes implicated in OI were screened for mutation. The function and structure of the mutant protein were predicted using bioinformatics analysis. The proband, a 9-month fetus, showed abnormal sonographic images. Disproportionately short and triangular face with blue sclera was noticed at birth. She can barely walk and suffered multiple fractures till 2-year old. Her mother appeared small stature, frequent fractures, blue sclera, and deformity of extremities. A heterozygous missense mutation c.1009G>T (p.G337C) in the COL1A2 gene was identified in her mother and her. Bioinformatics analysis showed p.G337 was well-conserved among multiple species and the mutation probably changed the structure and damaged the function of collagen. We suggest that the mutation p.G337C in the COL1A2 gene is pathogenic for OI by affecting the protein structure and the function of collagen. PMID:28953610

  5. Tissue-specific mosaicism for a lethal osteogenesis imperfecta COL1A1 mutation causes mild OI/EDS overlap syndrome.

    Science.gov (United States)

    Symoens, Sofie; Steyaert, Wouter; Demuynck, Lynn; De Paepe, Anne; Diderich, Karin E M; Malfait, Fransiska; Coucke, Paul J

    2017-04-01

    Type I collagen is the predominant protein of connective tissues such as skin and bone. Mutations in the type I collagen genes (COL1A1 and COL1A2) mainly cause osteogenesis imperfecta (OI). We describe a patient with clinical signs of Ehlers-Danlos syndrome (EDS), including fragile skin, easy bruising, recurrent luxations, and fractures resembling mild OI. Biochemical collagen analysis of the patients' dermal fibroblasts showed faint overmodification of the type I collagen bands, a finding specific for structural defects in type I collagen. Bidirectional Sanger sequencing detected an in-frame deletion in exon 44 of COL1A1 (c.3150_3158del), resulting in the deletion of three amino acids (p.Ala1053_Gly1055del) in the collagen triple helix. This COL1A1 mutation was hitherto identified in four probands with lethal OI, and never in EDS patients. As the peaks on the electropherogram corresponding to the mutant allele were decreased in intensity, we performed next generation sequencing of COL1A1 to study mosaicism in skin and blood. While approximately 9% of the reads originating from fibroblast gDNA harbored the COL1A1 deletion, the deletion was not detected in gDNA from blood. Most likely, the mild clinical symptoms observed in our patient can be explained by the mosaic state of the mutation. © 2017 Wiley Periodicals, Inc.

  6.  Mutations of noncollagen genes in osteogenesis imperfecta – implications of the gene products in collagen biosynthesis and pathogenesis of disease

    Directory of Open Access Journals (Sweden)

    Anna Galicka

    2012-06-01

    Full Text Available  Recent investigations revealed that the “brittle bone” phenotype in osteogenesis imperfecta (OI is caused not only by dominant mutations in collagen type I genes, but also by recessively inherited mutations in genes responsible for the post-translational processing of type I procollagen as well as for bone formation. The phenotype of patients with mutations in noncollagen genes overlaps with very severe type III and lethal type II OI caused by mutations in collagen genes. Mutations in genes that encode proteins involved in collagen prolyl 3-hydroxylation (P3H1/CRTAP/CyPB eliminated Pro986 hydroxylation and caused an increase in modification of collagen helix by prolyl 4-hydroxylase and lysyl hydroxylase. However, the importance of these disturbances in the disease pathomechanism is not known. Loss of complex proteins’ function as collagen chaperones may dominate the disease mechanism. The latest findings added to the spectrum of OI-causing and collagen-influencing factors other chaperones (HSP47 and FKBP65 and protein BMP-1, which emphasizes the complexity of collagen folding and secretion as well as their importance in bone formation. Furthermore, mutations in genes encoding transcription factor SP7/Osterix and pigment epithelium-derived factor (PEDF constitute a novel mechanism for OI, which is independent of changes in biosynthesis and processing of collagen.

  7. A case of fetal osteogenesis imperfecta type 2A: longitudinal observation of natural course in utero and pitfalls for prenatal ultrasound diagnosis.

    Science.gov (United States)

    Kimura, Ibuki; Araki, Ryota; Yoshizato, Toshiyuki; Miyamoto, Shingo

    2015-10-01

    We present a case of osteogenesis imperfecta (OI) type 2A in which a natural course in utero was observed from 23 weeks' gestation to term. At 23 weeks' gestation, a sonographic examination showed a cloverleaf skull-like head, a narrow thorax, and marked shortening of the long bones with bowing of the femurs and humeri. Follow-up examinations showed that the cloverleaf skull-like head was not evident at 28 weeks' gestation. Discontinuity of the ribs and femurs was observed at 26 and 30 weeks' gestation, respectively. This finding suggested bone fractures, which were confirmed by three-dimensional computed tomography at 32 weeks' gestation. Ultrasonographic findings of bones, including the long bones and calvarium, changed with advancing gestation during the second trimester. Characteristic features of OI type 2A were evident during the late second to early third trimesters. Repeated ultrasonographic examinations together with three-dimensional computed tomography are necessary for the definitive diagnosis of OI type 2A in the second trimester.

  8. Identification of a novel COL1A1 frameshift mutation, c.700delG, in a Chinese osteogenesis imperfecta family

    Science.gov (United States)

    Wang, Xiran; Pei, Yu; Dou, Jingtao; Lu, Juming; Li, Jian; Lv, Zhaohui

    2015-01-01

    Osteogenesis imperfecta (OI) is a family of genetic disorders associated with bone loss and fragility. Mutations associated with OI have been found in genes encoding the type I collagen chains. People with OI type I often produce insufficient α1-chain type I collagen because of frameshift, nonsense, or splice site mutations in COL1A1 or COL1A2. This report is of a Chinese daughter and mother who had both experienced two bone fractures. Because skeletal fragility is predominantly inherited, we focused on identifying mutations in COL1A1 and COL1A2 genes. A novel mutation in COL1A1, c.700delG, was detected by genomic DNA sequencing in the mother and daughter, but not in their relatives. The identification of this mutation led to the conclusion that they were affected by mild OI type I. Open reading frame analysis indicated that this frameshift mutation would truncate α1-chain type I collagen at residue p263 (p.E234KfsX264), while the wild-type protein would contain 1,464 residues. The clinical data were consistent with the patients’ diagnosis of mild OI type I caused by haploinsufficiency of α1-chain type I collagen. Combined with previous reports, identification of the novel mutation COL1A1-c.700delG in these patients suggests that additional genetic and environmental factors may influence the severity of OI. PMID:25983617

  9. Premature chain termination is a unifying mechanism for COL1A1 null alleles in osteogenesis imperfecta type I cell strains

    Energy Technology Data Exchange (ETDEWEB)

    Willing, M.C.; Deschenes, S.P.; Roberts, E.J. [Univ. of Iowa, Iowa City, IA (United States)] [and others

    1996-10-01

    Nonsense and frameshift mutations, which predict premature termination of translation, often cause a dramatic reduction in the amount of transcript from the mutant allele (nonsense-mediated mRNA decay). In some genes, these mutations also influence RNA splicing and induce skipping of the exon that contains the nonsense codon. To begin to dissect how premature termination alters the metabolism of RNA from the COL1A1 gene, we studied nonsense and frameshift mutations distributed over exons 11-49 of the gene. These mutations were originally identified in 10 unrelated families with osteogenesis imperfecta (OI) type I. We observed marked reduction in steady-state amounts of mRNA from the mutant allele in both total cellular and nuclear RNA extracts of cells from affected individuals, suggesting that nonsense-mediated decay of COL1A1 RNA is a nuclear phenomenon. Position of the mutation within the gene did not influence this observation. None of the mutations induced skipping of either the exon containing the mutation or, for the frameshifts, the downstream exons with the new termination sites. Our data suggest that nonsense and frameshift mutations throughout most of the COL1A1 gene result in a null allele, which is associated with the predictable mild clinical phenotype, OI type I. 42 refs., 6 figs., 1 tab.

  10. The Reversed Less Invasive Stabilisation System-Distal Femur Technique: Application in an Adult Patient with Osteogenesis Imperfecta Sustaining a Femoral Fracture.

    Science.gov (United States)

    Hanke, Markus S; Keel, Marius Johann; Todorski, Inga A; Bastian, Johannes Dominik

    2017-01-01

    The aim of this study was to report the surgical management and to discuss the options for fracture fixation in an adult patient with osteogenesis imperfecta (OI) who sustained a trochanteric femoral fracture after a simple fall from standing position. As a result of multiple fractures during childhood, this adult patient with OI presented with a short stature. The radiographs revealed a displaced, intertrochanteric fracture with subtrochanteric extension of the left femur. The intramedullary canal was narrow, the femur presented with a severe bowing deformity, and the bone quality was poor. The implant of choice was plating using the reversed less invasive stabilisation system-distal femur (LISS-DF) technique. This technique was introduced for the management of subtrochanteric fractures in the elderly with poor bone stock. In addition, a locking plate attached to the LISS-DF allowed for additional screw placement at the apex of the curvature of the femur although the plate was not in line with the femur at this site. Cerclages were used for metaphyseal reduction and fixation. 4-month postoperatively, the patient was ambulatory without any assistance with full weight bearing. At the latest follow-up 1-year postoperatively, the patient was still free of complaints and at her preinjury activity level. The presented technique was successful as a salvage procedure in a rare case of adult OI presenting with a femoral fracture with characteristics influencing the decision-making in treatment options.

  11. [Keratitis due to Acanthamoeba].

    Science.gov (United States)

    Pérez-Irezábal, Julio; Martínez, Inés; Isasa, Patricia; Barrón, Jorge

    2006-10-01

    Free-living amebae appertaining to the genus Acanthamoeba, Naegleria and Balamuthia are the most prevalent protozoa found in the environment. These amebae have a cosmopolitan distribution in soil, air and water, providing multiple opportunities for contacts with humans and animals, although they only occasionally cause disease. Acanthamoeba spp. are the causative agent of granulomatous amebic encephalitis, a rare and often fatal disease of the central nervous system, and amebic keratitis, a painful disease of the eyes. Keratitis usually follows a chronic course due to the delay in diagnosis and subsequent treatment. The clear increase in Acanthamoeba keratitis in the last 20 years is related to the use and deficient maintenance of contact lenses, and to swimming while wearing them. The expected incidence is one case per 30,000 contact lens wearers per year, with 88% of cases occurring in persons wearing hydrogel lenses. This review presents information on the morphology, life-cycle and epidemiology of Acanthamoeba, as well as on diagnostic procedures (culture), appropriate antimicrobial therapy, and prevention measures.

  12. Substitution of arginine for glycine at position 154 of the {alpha}1 chain of type I collagen in a variant of osteogenesis imperfecta: Comparison to previous cases with the same mutation

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, J.; Tromp, G.; Kuivaniemi, H.; Prockop, D.J. [Thomas Jefferson Univ., Philadelphia, PA (United States); Castells, S. [Univ. Hospital of Brooklyn, NY (United States)

    1996-01-11

    A substitution of arginine for glycine at amino acid position 154 of the {alpha}1(I) collagen chain was found in a father and his three children. The phenotype of the patients includes manifestations of types I and III/IV osteogenesis imperfecta, but appears to be milder than that of the previously described two unrelated patients that had the identical mutation in the {alpha}1(I) collagen chain. The variability in the phenotype raises the possibility of epistatic loci or environmental effects on expression of the disorder. 35 refs., 3 figs., 2 tabs.

  13. Local amino acid sequence patterns dominate the heterogeneous phenotype for the collagen connective tissue disease Osteogenesis Imperfecta resulting from Gly mutations.

    Science.gov (United States)

    Xiao, Jianxi; Yang, Zhangfu; Sun, Xiuxia; Addabbo, Rayna; Baum, Jean

    2015-10-01

    Osteogenesis Imperfecta (OI), a hereditary connective tissue disease in collagen that arises from a single Gly → X mutation in the collagen chain, varies widely in phenotype from perinatal lethal to mild. It is unclear why there is such a large variation in the severity of the disease considering the repeating (Gly-X-Y)n sequence and the uniform rod-like structure of collagen. We systematically evaluate the effect of local (Gly-X-Y)n sequence around the mutation site on OI phenotype using integrated bio-statistical approaches, including odds ratio analysis and decision tree modeling. We show that different Gly → X mutations have different local sequence patterns that are correlated with lethal and nonlethal phenotypes providing a mechanism for understanding the sensitivity of local context in defining lethal and non-lethal OI. A number of important trends about which factors are related to OI phenotypes are revealed by the bio-statistical analyses; most striking is the complementary relationship between the placement of Pro residues and small residues and their correlation to OI phenotype. When Pro is present or small flexible residues are absent nearby a mutation site, the OI case tends to be lethal; when Pro is present or small flexible residues are absent further away from the mutation site, the OI case tends to be nonlethal. The analysis also reveals the dominant role of local sequence around mutation sites in the Major Ligand Binding Regions that are primarily responsible for collagen binding to its receptors and shows that non-lethal mutations are highly predicted by local sequence considerations alone whereas lethal mutations are not as easily predicted and may be a result of more complex interactions. Understanding the sequence determinants of OI mutations will enhance genetic counseling and help establish which steps in the collagen hierarchy to target for drug therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta.

    Science.gov (United States)

    Cabral, Wayne A; Ishikawa, Masaki; Garten, Matthias; Makareeva, Elena N; Sargent, Brandi M; Weis, MaryAnn; Barnes, Aileen M; Webb, Emma A; Shaw, Nicholas J; Ala-Kokko, Leena; Lacbawan, Felicitas L; Högler, Wolfgang; Leikin, Sergey; Blank, Paul S; Zimmerberg, Joshua; Eyre, David R; Yamada, Yoshihiko; Marini, Joan C

    2016-07-01

    Recessive osteogenesis imperfecta (OI) is caused by defects in proteins involved in post-translational interactions with type I collagen. Recently, a novel form of moderately severe OI caused by null mutations in TMEM38B was identified. TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores. The molecular mechanisms by which TMEM38B mutations cause OI are unknown. We identified 3 probands with recessive defects in TMEM38B. TRIC-B protein is undetectable in proband fibroblasts and osteoblasts, although reduced TMEM38B transcripts are present. TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated with deficient store-operated calcium entry, although SERCA and IP3R have normal stability. Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency, supporting a role for TRIC-B in the kinetics of ER calcium depletion and recovery. The disturbed Ca2+ flux causes ER stress and increased BiP, and dysregulates synthesis of proband type I collagen at multiple steps. Collagen helical lysine hydroxylation is reduced, while telopeptide hydroxylation is increased, despite increased LH1 and decreased Ca2+-dependent FKBP65, respectively. Although PDI levels are maintained, procollagen chain assembly is delayed in proband cells. The resulting misfolded collagen is substantially retained in TRIC-B null cells, consistent with a 50-70% reduction in secreted collagen. Lower-stability forms of collagen that elude proteasomal degradation are not incorporated into extracellular matrix, which contains only normal stability collagen, resulting in matrix insufficiency. These data support a role for TRIC-B in intracellular Ca2+ homeostasis, and demonstrate that absence of TMEM38B causes OI by dysregulation of calcium flux kinetics in the ER, impacting multiple collagen-specific chaperones and modifying enzymes.

  15. Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta.

    Directory of Open Access Journals (Sweden)

    Wayne A Cabral

    2016-07-01

    Full Text Available Recessive osteogenesis imperfecta (OI is caused by defects in proteins involved in post-translational interactions with type I collagen. Recently, a novel form of moderately severe OI caused by null mutations in TMEM38B was identified. TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores. The molecular mechanisms by which TMEM38B mutations cause OI are unknown. We identified 3 probands with recessive defects in TMEM38B. TRIC-B protein is undetectable in proband fibroblasts and osteoblasts, although reduced TMEM38B transcripts are present. TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated with deficient store-operated calcium entry, although SERCA and IP3R have normal stability. Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency, supporting a role for TRIC-B in the kinetics of ER calcium depletion and recovery. The disturbed Ca2+ flux causes ER stress and increased BiP, and dysregulates synthesis of proband type I collagen at multiple steps. Collagen helical lysine hydroxylation is reduced, while telopeptide hydroxylation is increased, despite increased LH1 and decreased Ca2+-dependent FKBP65, respectively. Although PDI levels are maintained, procollagen chain assembly is delayed in proband cells. The resulting misfolded collagen is substantially retained in TRIC-B null cells, consistent with a 50-70% reduction in secreted collagen. Lower-stability forms of collagen that elude proteasomal degradation are not incorporated into extracellular matrix, which contains only normal stability collagen, resulting in matrix insufficiency. These data support a role for TRIC-B in intracellular Ca2+ homeostasis, and demonstrate that absence of TMEM38B causes OI by dysregulation of calcium flux kinetics in the ER, impacting multiple collagen-specific chaperones and modifying enzymes.

  16. Scoliosis in osteogenesis imperfecta caused by COL1A1/COL1A2 mutations - genotype-phenotype correlations and effect of bisphosphonate treatment.

    Science.gov (United States)

    Sato, Atsuko; Ouellet, Jean; Muneta, Takeshi; Glorieux, Francis H; Rauch, Frank

    2016-05-01

    Bisphosphonates are widely used to treat children with osteogenesis imperfecta (OI), a bone fragility disorder that is most often caused by mutations in COL1A1 or COL1A2. However, it is unclear whether this treatment decreases the risk of developing scoliosis. We retrospectively evaluated spine radiographs and charts of 437 patients (227 female) with OI caused by mutations in COL1A1 or COL1A2 and compared the relationship between scoliosis, genotype and bisphosphonate treatment history. At the last follow-up (mean age 11.9 [SD: 5.9] years), 242 (55%) patients had scoliosis. The prevalence of scoliosis was highest in OI type III (89%), followed by OI type IV (61%) and OI type I (36%). Moderate to severe scoliosis (Cobb angle ≥25°) was rare in individuals with COL1A1 haploinsufficiency mutations but was present in about two fifth of patients with triple helical glycine substitutions or C-propeptide mutations. During the first 2 to 4years of bisphosphonate therapy, patients with OI type III had lower Cobb angle progression rates than before bisphosphonate treatment, whereas in OI types I and IV bisphosphonate treatment was not associated with a change in Cobb angle progression rates. At skeletal maturity, the prevalence of scoliosis (Cobb angle >10°) was similar in patients who had started bisphosphonate treatment early in life (before 5.0years of age) and in patients who had started therapy later (after the age of 10.0years) or had never received bisphosphonate therapy. Bisphosphonate treatment decreased progression rate of scoliosis in OI type III but there was no evidence of a positive effect on scoliosis in OI types I and IV. The prevalence of scoliosis at maturity was not influenced by the bisphosphonate treatment history in any OI type. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta

    Science.gov (United States)

    Cabral, Wayne A.; Ishikawa, Masaki; Garten, Matthias; Makareeva, Elena N.; Sargent, Brandi M.; Weis, MaryAnn; Barnes, Aileen M.; Webb, Emma A.; Shaw, Nicholas J.; Ala-Kokko, Leena; Lacbawan, Felicitas L.; Högler, Wolfgang; Leikin, Sergey; Blank, Paul S.; Zimmerberg, Joshua; Eyre, David R.; Yamada, Yoshihiko; Marini, Joan C.

    2016-01-01

    Recessive osteogenesis imperfecta (OI) is caused by defects in proteins involved in post-translational interactions with type I collagen. Recently, a novel form of moderately severe OI caused by null mutations in TMEM38B was identified. TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores. The molecular mechanisms by which TMEM38B mutations cause OI are unknown. We identified 3 probands with recessive defects in TMEM38B. TRIC-B protein is undetectable in proband fibroblasts and osteoblasts, although reduced TMEM38B transcripts are present. TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated with deficient store-operated calcium entry, although SERCA and IP3R have normal stability. Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency, supporting a role for TRIC-B in the kinetics of ER calcium depletion and recovery. The disturbed Ca2+ flux causes ER stress and increased BiP, and dysregulates synthesis of proband type I collagen at multiple steps. Collagen helical lysine hydroxylation is reduced, while telopeptide hydroxylation is increased, despite increased LH1 and decreased Ca2+-dependent FKBP65, respectively. Although PDI levels are maintained, procollagen chain assembly is delayed in proband cells. The resulting misfolded collagen is substantially retained in TRIC-B null cells, consistent with a 50–70% reduction in secreted collagen. Lower-stability forms of collagen that elude proteasomal degradation are not incorporated into extracellular matrix, which contains only normal stability collagen, resulting in matrix insufficiency. These data support a role for TRIC-B in intracellular Ca2+ homeostasis, and demonstrate that absence of TMEM38B causes OI by dysregulation of calcium flux kinetics in the ER, impacting multiple collagen-specific chaperones and modifying enzymes. PMID:27441836

  18. A founder mutation in LEPRE1 carried by 1.5% of West Africans and 0.4% of African Americans causes lethal recessive osteogenesis imperfecta.

    Science.gov (United States)

    Cabral, Wayne A; Barnes, Aileen M; Adeyemo, Adebowale; Cushing, Kelly; Chitayat, David; Porter, Forbes D; Panny, Susan R; Gulamali-Majid, Fizza; Tishkoff, Sarah A; Rebbeck, Timothy R; Gueye, Serigne M; Bailey-Wilson, Joan E; Brody, Lawrence C; Rotimi, Charles N; Marini, Joan C

    2012-05-01

    Deficiency of prolyl 3-hydroxylase 1, encoded by LEPRE1, causes recessive osteogenesis imperfecta (OI). We previously identified a LEPRE1 mutation exclusively in African Americans and contemporary West Africans. We hypothesized that this allele originated in West Africa and was introduced to the Americas with the Atlantic slave trade. We aimed to determine the frequency of carriers for this mutation among African Americans and West Africans, and the mutation origin and age. Genomic DNA was screened for the mutation using PCR and restriction digestion, and a custom TaqMan genomic single-nucleotide polymorphism assay. The mutation age was estimated using microsatellites and short tandem repeats spanning 4.2 Mb surrounding LEPRE1 in probands and carriers. Approximately 0.4% (95% confidence interval: 0.22-0.68%) of Mid-Atlantic African Americans carry this mutation, estimating recessive OI in 1/260,000 births in this population. In Nigeria and Ghana, 1.48% (95% confidence interval: 0.95-2.30%) of unrelated individuals are heterozygous carriers, predicting that 1/18,260 births will be affected with recessive OI, equal to the incidence of de novo dominant OI. The mutation was not detected in Africans from surrounding countries. All carriers shared a haplotype of 63-770 Kb, consistent with a single founder for this mutation. Using linkage disequilibrium analysis, the mutation was estimated to have originated between 650 and 900 years before present (1100-1350 CE). We identified a West African founder mutation for recessive OI in LEPRE1. Nearly 1.5% of Ghanians and Nigerians are carriers. The estimated age of this allele is consistent with introduction to North America via the Atlantic slave trade (1501-1867 CE).

  19. Mutations in the COL1A1 and COL1A2 genes associated with osteogenesis imperfecta (OI) types I or III.

    Science.gov (United States)

    Augusciak-Duma, Aleksandra; Witecka, Joanna; Sieron, Aleksander L; Janeczko, Magdalena; Pietrzyk, Jacek J; Ochman, Karolina; Galicka, Anna; Borszewska-Kornacka, Maria K; Pilch, Jacek; Jakubowska-Pietkiewicz, Elzbieta

    2018-03-15

    Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined. Mutations were found in exons 2, 22, 50 and in introns 13 and 51 of the COL1A1 gene. In COL1A2, one mutation was identified in exon 22. Deletion type mutations in COL1A1 that resulted in OI type I had no effect on collagen type I secretion, nor on its intracellular accumulation. Also, a single base substitution in I13 (c.904-9 G>T) was associated with the OI type I. The OI type III was associated with a single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly→ Cys in the central part of the triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of the heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation into procollagen type I. The results obtained shall help in genetic counseling of OI patients and provide a rational support for making informed, life important decisions by them and their families.

  20. Evaluation of Fracture and Osteotomy Union in the Setting of Osteogenesis Imperfecta: Reliability of the Modified Radiographic Union Score for Tibial Fractures (RUST).

    Science.gov (United States)

    Franzone, Jeanne M; Finkelstein, Mark S; Rogers, Kenneth J; Kruse, Richard W

    2017-09-08

    Evaluation of the union of osteotomies and fractures in patients with osteogenesis imperfecta (OI) is a critical component of patient care. Studies of the OI patient population have so far used varied criteria to evaluate bony union. The radiographic union score for tibial fractures (RUST), which was subsequently revised to the modified RUST, is an objective standardized method of evaluating fracture healing. We sought to evaluate the reliability of the modified RUST in the setting of the tibias of patients with OI. Tibial radiographs of 30 patients with OI fractures, or osteotomies were scored by 3 observers on 2 separate occasions. Each of the 4 cortices was given a score (1=no callus, 2=callus present, 3=bridging callus, and 4=remodeled, fracture not visible) and the modified RUST is the sum of these scores (range, 4 to 16). The interobserver and intraobserver reliabilities were evaluated using intraclass coefficients (ICC) with 95% confidence intervals. The ICC representing the interobserver reliability for the first iteration of scores was 0.926 (0.864 to 0.962) and for the second series was 0.915 (0.845 to 0.957). The ICCs representing the intraobserver reliability for each of the 3 reviewers for the measurements in series 1 and 2 were 0.860 (0.707 to 0.934), 0.994 (0.986 to 0.997), and 0.974 (0.946 to 0.988). The modified RUST has excellent interobserver and intraobserver reliability in the setting of OI despite challenges related to the poor quality of the bone and its dysplastic nature. The application and routine use of the modified RUST in the OI population will help standardize our evaluation of osteotomy and fracture healing. Level III-retrospective study of nonconsecutive patients.

  1. Efficacy of Bisphosphonates on Bone Mineral Density and Fracture Rate in Patients With Osteogenesis Imperfecta: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Shi, Chang Gui; Zhang, Ying; Yuan, Wen

    2016-01-01

    Epidemiological evidence suggests that bisphosphonates are the most promising drugs for patients with osteogenesis imperfecta (OI). However, data on this issue are controversial. We conducted a meta-analysis to assess the efficacy of bisphosphonates on bone mineral density (BMD) and fracture rate in patients with OI. Electronic databases were searched to find relevant studies. Two reviewers independently identified relevant randomized controlled trials, which evaluated the efficacy of bisphosphonates in patients with OI. Outcome measures were fracture incidence and BMD changes in different skeletal sites. A total of 9 randomized controlled trials including 557 patients were identified. Meta-analysis demonstrated a beneficial effect of bisphosphonates on spine BMD Z-score and area BMD (in grams per square centimeter) %. Patients treated with bisphosphonates had a lower risk of fracture [risk ratio (RR) = 0.80; 95% confidence interval (CI): 0.66-0.97] compared with those in control groups. In children, bisphosphonates were efficacious in reducing fractures (RR = 0.80; 95% CI: 0.66-0.97), where in adults, bisphosphonates seemed equivalent to placebo in that respect (RR = 0.82; 95% CI: 0.42-1.59), although no significant difference was noted between these 2 RRs (test of interaction, z = -0.07; P = 0.94). There was also no significant difference in reducing fractures between oral and intravenous bisphosphonates (P = 0.23). This study showed that bisphosphonates could increase the BMD and reduce the risk of facture in patients with OI. There was no enough evidence to identify any differences in efficacy between oral and intravenous bisphosphonates on fracture reduction, as well as between children and adults.

  2. The Severity of Osteogenesis Imperfecta and Type I Collagen Pattern in Human Skin as Determined by Nonlinear Microscopy: Proof of Principle of a Diagnostic Method

    Science.gov (United States)

    Pedroni, Marcus Vinícius; Steiner, Carlos E.; Pelegati, Vitor B.; de Thomaz, Andre A.; Carvalho, Hernandes F.; Cesar, Carlos L.

    2013-01-01

    Background The confirmatory diagnosis of Osteogenesis Imperfecta (OI) requires invasive, commonly bone biopsy, time consuming and destructive methods. This paper proposes an alternative method using a combination of two-photon excitation fluorescence (TPEF) and second-harmonic generation (SHG) microscopies from easily obtained human skin biopsies. We show that this method can distinguish subtypes of human OI. Methodology/Principal Findings Different aspects of collagen microstructure of skin fresh biopsies and standard H&E-stained sections of normal and OI patients (mild and severe forms) were distinguished by TPEF and SHG images. Moreover, important differences between subtypes of OI were identified using different methods of quantification such as collagen density, ratio between collagen and elastic tissue, and gray-level co-occurrence matrix (GLCM) image-pattern analysis. Collagen density was lower in OI dermis, while the SHG/autofluorescence index of the dermis was significantly higher in OI as compared to that of the normal skin. We also showed that the energy value of GLCM texture analysis is useful to discriminate mild from severe OI and from normal skin. Conclusions/Significance This work demonstrated that nonlinear microscopy techniques in combination with image-analysis approaches represent a powerful tool to investigate the collagen organization in skin dermis in patients with OI and has the potential to distinguish the different types of OI. The procedure outlined in this paper requires a skin biopsy, which is almost painless as compared to the bone biopsy commonly used in conventional methods. The data presented here complement existing clinical diagnostic techniques and can be used as a diagnostic procedure to confirm the disease, evaluate its severity and treatment efficacy. PMID:23869235

  3. Non lethal Raine syndrome and differential diagnosis.

    Science.gov (United States)

    Elalaoui, Siham Chafai; Al-Sheqaih, Nada; Ratbi, Ilham; Urquhart, Jill E; O'Sullivan, James; Bhaskar, Sanjeev; Williams, Simon S; Elalloussi, Mustapha; Lyahyai, Jaber; Sbihi, Leila; Cherkaoui Jaouad, Imane; Sbihi, Abdelhafid; Newman, William G; Sefiani, Abdelaziz

    2016-11-01

    Raine syndrome is a rare autosomal recessive bone dysplasia characterized by characteristic facial features with exophthalmos and generalized osteosclerosis. Amelogenesis imperfecta, hearing loss, seizures, and intracerebral calcification are apparent in some affected individuals. Originally, Raine syndrome was originally reported as a lethal syndrome. However, recently a milder phenotype, compatible with life, has been described. Biallelic variants inFAM20C, encoding aGolgi casein kinase involved in biomineralisation, have been identified in affected individuals. We report here a consanguineous Moroccan family with two affected siblingsa girl aged 18 and a boy of 15years. Clinical features, including learning disability, seizures and amelogenesis imperfecta, initially suggested a diagnosis of Kohlschutter-Tonz syndrome. However,a novel homozygous FAM20Cvariantc.676T > A, p.(Trp226Arg) was identified in the affected siblings. Our report reinforces that Raine syndrome is compatible with life, and that mild hypophosphatemia and amelogenesis imperfecta are key features of the attenuated form. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Correlations Between Bone Mechanical Properties and Bone Composition Parameters in Mouse Models of Dominant and Recessive Osteogenesis Imperfecta and the Response to Anti-TGF-β Treatment.

    Science.gov (United States)

    Bi, Xiaohong; Grafe, Ingo; Ding, Hao; Flores, Rene; Munivez, Elda; Jiang, Ming Ming; Dawson, Brian; Lee, Brendan; Ambrose, Catherine G

    2017-02-01

    Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by brittle bones that are prone to fracture. Although previous studies in animal models investigated the mechanical properties and material composition of OI bone, little work has been conducted to statistically correlate these parameters to identify key compositional contributors to the impaired bone mechanical behaviors in OI. Further, although increased TGF-β signaling has been demonstrated as a contributing mechanism to the bone pathology in OI models, the relationship between mechanical properties and bone composition after anti-TGF-β treatment in OI has not been studied. Here, we performed follow-up analyses of femurs collected in an earlier study from OI mice with and without anti-TGF-β treatment from both recessive (Crtap -/- ) and dominant (Col1a2 +/P.G610C ) OI mouse models and WT mice. Mechanical properties were determined using three-point bending tests and evaluated for statistical correlation with molecular composition in bone tissue assessed by Raman spectroscopy. Statistical regression analysis was conducted to determine significant compositional determinants of mechanical integrity. Interestingly, we found differences in the relationships between bone composition and mechanical properties and in the response to anti-TGF-β treatment. Femurs of both OI models exhibited increased brittleness, which was associated with reduced collagen content and carbonate substitution. In the Col1a2 +/P.G610C femurs, reduced hydroxyapatite crystallinity was also found to be associated with increased brittleness, and increased mineral-to-collagen ratio was correlated with increased ultimate strength, elastic modulus, and bone brittleness. In both models of OI, regression analysis demonstrated that collagen content was an important predictor of the increased brittleness. In summary, this work provides new insights into the relationships between bone composition and material properties in

  5. Decreased fracture rate, pharmacogenetics and BMD response in 79 Swedish children with osteogenesis imperfecta types I, III and IV treated with Pamidronate.

    Science.gov (United States)

    Lindahl, K; Kindmark, A; Rubin, C-J; Malmgren, B; Grigelioniene, G; Söderhäll, S; Ljunggren, Ö; Åström, E

    2016-06-01

    Osteogenesis imperfecta (OI) is an inherited heterogeneous bone fragility disorder, usually caused by collagen I mutations. It is well established that bisphosphonate treatment increases lumbar spine (LS) bone mineral density (BMD), as well as improves vertebral geometry in severe OI; however, fracture reduction has been difficult to prove, pharmacogenetic studies are scarce, and it is not known at which age, or severity of disease, treatment should be initiated. COL1A1 and COL1A2 were analyzed in 79 children with OI (type I n=33, type III n=25 and type IV n=21) treated with Pamidronate. Data on LS BMD, height, and radiologically confirmed non-vertebral and vertebral fractures were collected prior to, and at several time points during treatment. An increase in LS BMD Z-score was observed for all types of OI, and a negative correlation to Δ LS BMD was observed for both age and LS BMD Z-score at treatment initiation. Supine height Z-scores were not affected by Pamidronate treatment, The fracture rate was reduced for all OI types at all time points during treatment (overall p4yrs Pamidronate. Twice as many boys as girls with OI type I were treated with Pamidronate, and the fracture rate the year prior treatment was 2.2 times higher for boys (p=0.0236). Greater Δ LS BMD, but smaller Δ fracture numbers were observed on Pamidronate for helical glycine mutations in COL1A1 vs. COL1A2. Vertebral compression fractures did not progress in any individual during treatment; however, they did not improve in 9%, and these individuals were all >11years of age at treatment initiation (p<0.0001). Pamidronate treatment in children with all types of OI increased LS BMD, decreased fracture rate, and improved vertebral compression fractures. Fracture reduction was prompt and maintained during treatment, irrespective of age at treatment initiation and collagen I mutation type. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Abnormal Type I Collagen Post-translational Modification and Crosslinking in a Cyclophilin B KO Mouse Model of Recessive Osteogenesis Imperfecta

    Science.gov (United States)

    Cabral, Wayne A.; Perdivara, Irina; Weis, MaryAnn; Terajima, Masahiko; Blissett, Angela R.; Chang, Weizhong; Perosky, Joseph E.; Makareeva, Elena N.; Mertz, Edward L.; Leikin, Sergey; Tomer, Kenneth B.; Kozloff, Kenneth M.; Eyre, David R.; Yamauchi, Mitsuo; Marini, Joan C.

    2014-01-01

    Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause recessively inherited osteogenesis imperfecta type IX, a moderately severe to lethal bone dysplasia. To investigate the role of CyPB in collagen folding and post-translational modifications, we generated Ppib−/− mice that recapitulate the OI phenotype. Knock-out (KO) mice are small, with reduced femoral areal bone mineral density (aBMD), bone volume per total volume (BV/TV) and mechanical properties, as well as increased femoral brittleness. Ppib transcripts are absent in skin, fibroblasts, femora and calvarial osteoblasts, and CyPB is absent from KO osteoblasts and fibroblasts on western blots. Only residual (2–11%) collagen prolyl 3-hydroxylation is detectable in KO cells and tissues. Collagen folds more slowly in the absence of CyPB, supporting its rate-limiting role in folding. However, treatment of KO cells with cyclosporine A causes further delay in folding, indicating the potential existence of another collagen PPIase. We confirmed and extended the reported role of CyPB in supporting collagen lysyl hydroxylase (LH1) activity. Ppib−/− fibroblast and osteoblast collagen has normal total lysyl hydroxylation, while increased collagen diglycosylation is observed. Liquid chromatography/mass spectrometry (LC/MS) analysis of bone and osteoblast type I collagen revealed site-specific alterations of helical lysine hydroxylation, in particular, significantly reduced hydroxylation of helical crosslinking residue K87. Consequently, underhydroxylated forms of di- and trivalent crosslinks are strikingly increased in KO bone, leading to increased total crosslinks and decreased helical hydroxylysine- to lysine-derived crosslink ratios. The altered

  7. Effect of anti-sclerostin therapy and osteogenesis imperfecta on tissue-level properties in growing and adult mice while controlling for tissue age.

    Science.gov (United States)

    Sinder, Benjamin P; Lloyd, William R; Salemi, Joseph D; Marini, Joan C; Caird, Michelle S; Morris, Michael D; Kozloff, Kenneth M

    2016-03-01

    Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as osteogenesis imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly➔Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2-4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages>3wks) and rapidly growing Brtl/+ (at tissue ages>4wks) mice compared to WT. At identical tissue ages defined by fluorescent labels, adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and

  8. Hazards to Effective Due Diligence

    Directory of Open Access Journals (Sweden)

    Michael Benoliel

    2015-03-01

    Full Text Available It is not surprising that many business deals fail to realize their expected future value because some deal makers fail to perform effective due diligence. Successful deal makers, however, know that due diligence is one of the most important tasks in successful deal making. Thus, they avoid the psychological and contextual traps that cause poor due diligence. In this article, I describe the hazards – the psychological biases and contextual factors – that might affect the due diligence task. These hazards include information availability bias; confirmation bias; overconfidence bias; time pressure; self-interested agents; deal fever; narrow focus; and complexity. Following this review, I provide a number of suggestions to help deal makers and organizations overcome these hazards.

  9. Amelogenins as potential buffers during secretory-stage amelogenesis

    NARCIS (Netherlands)

    Guo, J.; Lyaruu, D.M.; Takano, Y.; Gibson, C.W.; Denbesten, P.K.; Bronckers, A.L.

    2015-01-01

    Amelogenins are the most abundant protein species in forming dental enamel, taken to regulate crystal shape and crystal growth. Unprotonated amelogenins can bind protons, suggesting that amelogenins could regulate the pH in enamel in situ. We hypothesized that without amelogenins the enamel would

  10. Autoerotic death due to electrocution

    Directory of Open Access Journals (Sweden)

    Piotr Arkuszewski

    2014-08-01

    Full Text Available Autoerotic death is a very rare case in forensic medicine. It is usually caused by asphyxia, but other reasons are also possible. Herein we present a case of autoerotic death due to electrocution caused by a self-made electrical device. The device was constructed to increase sexual feelings through stimulation of the scrotal area.

  11. Fast Facts on Osteogenesis Imperfecta

    Science.gov (United States)

    ... Classic Awareness Week Fine Wines Strong Bones Bone China Tea Blue Jeans for Better Bones Upcoming Events ... band seen on x-rays adjacent to the growth plate of the long bones. Unusually large calluses ( ...

  12. Myths about OI (Osteogenesis Imperfecta)

    Science.gov (United States)

    ... Unbreakable Spirit® OI Golf Classic Awareness Week Fine Wines Strong Bones Bone China Tea Blue Jeans for Better Bones Upcoming Events Online Store Facts About OI Types of OI Myths About OI OI ...

  13. Maculopathy due to drug inhalation.

    Science.gov (United States)

    Asensio-Sánchez, V M; Gonzalez-Buendia, L; Marcos-Fernández, M

    2014-08-01

    A case of maculopathy due to "poppers" is described. Poppers is a drug composed of various forms of alkyl nitrite. A 39 year-old man, who had been using poppers for years, was seen in the clinic with phosphenes, reduced visual acuity and central scotoma. The SD-OCT in the right eye showed disruption at the level of the IS/OS junction line. The SD-OCT scan in the left eye showed an outer rectangular retinal hole and an outer retinal cyst. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  14. Avaliação clínica, radiográfica e laboratorial de pacientes com osteogênese imperfeita Clinical, radiographic and laboratory evaluation of patients with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Cláudio Santili

    2005-08-01

    Full Text Available OBJETIVOS: A osteogênese imperfeita (OI é uma doença genética, caracterizando-se por alterações no colágeno do tipo I, que determinam um espectro amplo de alterações clínicas, como a dentinogênese imperfeita e escleras azuladas. O objetivo deste estudo é estabelecer uma correlação prática no diagnóstico diferencial intergrupos dentro da classificação de Sillence et al. (1979. MÉTODOS: Foram avaliados 22 pacientes mediante critérios clínicos e radiográficos. Após, a subdivisão de acordo com os tipos de Sillence et al. (1979, os pacientes foram também submetidos à avaliação laboratorial e à densitometria óssea. RESULTADOS: Os dados significantes para diferenciação entre os tipos da doença foram a estatura, o número total de fraturas por indivíduo e a densitometria óssea. O cálcio sérico não diferencia os tipos da doença. CONCLUSÕES: Características como a deambulação, a estatura e a densitometria óssea podem auxiliar na diferenciação entre os subtipos dos portadores da doença, repercutindo diretamente no estabelecimento do seu prognóstico.BACKGROUND: Osteogenesis imperfecta is a genetic disorder characterized by defects in type I collagen. The main symptom is bone fragility and susceptibility to fractures. Other clinical findings are dentinogenesis imperfecta, blue sclera, early deafness and joint laxity. The purpose of this paper is to establish a practical relationship of the clinical differences between the Sillence's groups. METHODS: 22 patients were classified according to Sillence et al criteria and submitted to laboratory tests including blood calcium level and bone densitometry. RESULTS: All clinical and laboratory differences were discussed in the text. CONCLUSIONS: Differences such as results that were found in walking ability, height and bone densitometry were significant and may help to classify patients and to establish prognosis.

  15. [Infections due to Mycobacterium simiae].

    Science.gov (United States)

    García-Martos, Pedro; García-Agudo, Lidia; González-Moya, Enrique; Galán, Fátima; Rodríguez-Iglesias, Manuel

    2015-10-01

    Mycobacterium simiae is a slow-growing photochromogenic environmental mycobacterium, first described in 1965. Rarely associated with human infections, possibly due to its limited pathogenicity, it mainly produces lung infection in immunocompetent elderly patients with underlying lung disease, and in disseminated infections in immunosuppressed young patients with AIDS. A microbiological culture is needed to confirm the clinical suspicion, and genetic sequencing techniques are essential to correctly identify the species. Treating M. simiae infections is complicated, owing to the multiple resistance to tuberculous drugs and the lack of correlation between in vitro susceptibility data and in vivo response. Proper treatment is yet to be defined, but must include clarithromycin combined with other antimicrobials such as moxifloxacin and cotrimoxazole. It is possible that M. simiae infections are undiagnosed. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  16. Occupational injuries due to violence.

    Science.gov (United States)

    Hales, T; Seligman, P J; Newman, S C; Timbrook, C L

    1988-06-01

    Each year in the United States, an estimated 800 to 1,400 people are murdered at work, and an unknown number of nonfatal injuries due to workplace violence occur. Based on Ohio's workers' compensation claims from 1983 through 1985, police officers, gasoline service station employees, employees of the real estate industry, and hotel/motel employees were found to be at the highest risk for occupational violent crime (OVC) injury and death. Grocery store employees, specifically those working in convenience food stores, and employees of the real estate industry had the most reported rapes. Four previously unidentified industries at increased risk of employee victimization were described. Identification of industries and occupations at high risk for crime victimization provides the opportunity to focus preventive strategies to promote employee safety and security in the workplace.

  17. Single fatherhood due to cancer.

    Science.gov (United States)

    Yopp, Justin M; Rosenstein, Donald L

    2012-12-01

    Cancer is a leading cause of widowed fatherhood in the USA. Fathers whose spouses have died from cancer constitute a potentially vulnerable population as they adjust to their role as sole or primary caregiver while managing their own grief and that of their children. The importance of addressing the psychological needs of widowed fathers is underscored by data showing that father's coping and emotional availability are closely tied to their bereaved children's mental health. Surprisingly, scant attention has been given to the phenomenon of widowed fatherhood with virtually no clinical resources or research studies devoted to fathers who have lost their wives to cancer. This commentary highlights key challenges facing this underserved population of widowers and calls for development of research agendas and clinical interventions for single fathers due to cancer. Copyright © 2011 John Wiley & Sons, Ltd.

  18. APPENDICULAR INVAGINATION DUE TO ENDOMETRIOSIS

    Directory of Open Access Journals (Sweden)

    Vasja Kruh

    2003-12-01

    Full Text Available Background. Invagination of the vermiform appendix is a very rare occurrence. We summarize epidemiologic and etiologic factors, types of classification, symtomatology, diagnostic features and treatment.Patients and treatment. The authors present 49-years old female with long-standing abdominal pains, who came in our hospital due to acute exacerbation with sever abdominal pain. Because of progressive symptoms and sensitivity in the right-lower abdominal quadrant a diagnostic laparoscopy was performed. An anomaly of cecum and the absence of appendix vermiformis have forced us to proceed with laparotomy in McBurnay point. After cecotomy an invaginated gangrenous appendix was found. The histological examination revealed endometriosis.Conclusions. By presenting this extremely rare pathology we also want to emphasize the important role of diagnostic laparoscopy in front of acute abdomen.

  19. Onycomycosis due to artificial nails.

    Science.gov (United States)

    Shemer, A; Trau, H; Davidovici, B; Grunwald, M H; Amichai, B

    2008-08-01

    The use of artificial nails (ANs) as part of nail-care cosmetics is very popular. Several side effects and complications, such as contact dermatitis and bacterial and fungal infections, have been reported in patients using ANs. Objective The purpose of this study was to identify the fungal pathogens in nail abnormalities appearing in patients with ANs. We evaluated 68 patients suffering from nail changes and paronychia, which appear after removal of ANs. Mycological samples were obtained from two sites: distal parts of the involved nail and the proximal nail fold. KOH examination and fungal culture were used for detection and identification of fungal infection. Mycological results from the distal part of the nail showed positive KOH test in 57 cases (83.8%), and culture was positive in 67 patients (98.5%). Mycological results obtained from the proximal nail fold showed positive KOH test in 36 patients (52.9%); in 36 of the cases, culture was positive. Candida spp. were the most common pathogen. Both KOH and culture results were significantly better while sampling from the distal part of the nail compared with sampling from the proximal nail fold (P = 0.0001). Onychomycosis was found to be very common in nail changes due to ANs, leading to an increased risk of transmitting microbial infections. Therefore, health care personnel and workers in the food industry should avoid using ANs.

  20. [Nephropathy due to Puumala hantavirus].

    Science.gov (United States)

    Dandolo, A; Prajs, N; Lizop, M

    2014-12-01

    Hemorrhagic fever with renal syndrome (HFRS) is due to an infection by the virus of the Hantavirus genus. Rodent hosts of Hantavirus are present in restricted areas in France; consequently, there are ecological niches and microepidemics of human Hantavirus infections. A HFRS case was diagnosed in the Paris region. The 11-year-old child had an acute debut fever-persistent despite antipyretic medication-asthenia, headache, abdominal pain, myalgia, thrombocytopenia, as well as renal failure with proteinuria. The diagnosis was made with a relevant clinical history and the specific serology of Puumala hantavirus. Therefore, a kidney biopsy was not necessary. What was interesting was the diagnostic approach because of the difference between the place and time of contamination and where the child became ill and developed the symptoms. The child was infected by Puumala hantavirus in Les Ardennes, a high-risk area, but became ill in the Paris region, an area with no prevalence. We review Hantavirus infections in France and its differential diagnosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.