WorldWideScience

Sample records for amelogenesis imperfecta due

  1. Genetics Home Reference: amelogenesis imperfecta

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Amelogenesis imperfecta Amelogenesis imperfecta Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Amelogenesis imperfecta is a disorder of tooth development. This ...

  2. Amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    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.

  3. Enamel formation and amelogenesis imperfecta.

    Science.gov (United States)

    Hu, Jan C-C; Chun, Yong-Hee P; Al Hazzazzi, Turki; Simmer, James P

    2007-01-01

    Dental enamel is the epithelial-derived hard tissue covering the crowns of teeth. It is the most highly mineralized and hardest tissue in the body. Dental enamel is acellular and has no physiological means of repair outside of the protective and remineralization potential provided by saliva. Enamel is comprised of highly organized hydroxyapatite crystals that form in a defined extracellular space, the contents of which are supplied and regulated by ameloblasts. The entire process is under genetic instruction. The genetic control of amelogenesis is poorly understood, but requires the activities of multiple components that are uniquely important for dental enamel formation. Amelogenesis imperfecta (AI) is a collective designation for the variety of inherited conditions displaying isolated enamel malformations, but the designation is also used to indicate the presence of an enamel phenotype in syndromes. Recently, genetic studies have demonstrated the importance of genes encoding enamel matrix proteins in the etiology of isolated AI. Here we review the essential elements of dental enamel formation and the results of genetic analyses that have identified disease-causing mutations in genes encoding enamel matrix proteins. In addition, we provide a fresh perspective on the roles matrix proteins play in catalyzing the biomineralization of dental enamel. Copyright 2007 S. Karger AG, Basel.

  4. Multiple Unerupted Teeth with Amelogenesis Imperfecta in Siblings

    OpenAIRE

    Shruthi Hegde

    2012-01-01

    Amelogenesis imperfecta encompasses a group of inherited abnormalities that are generally considered to primarily affect the formation and/or calcification of enamel. This case report describes the unusual presentation of amelogenesis imperfecta in siblings as multiple unerupted teeth, multiple pulpal calcifications, and multiple dilacerations of roots along with the defect in the enamel. The intent of our report is to highlight a rare co-occurrence of amelogenesis imperfecta with multiple mo...

  5. Association of Amelogenesis Imperfecta and Bartter's Syndrome.

    Science.gov (United States)

    Kumar, A C V; Alekya, V; Krishna, M S V V; Alekya, K; Aruna, M; Reddy, M H K; Sangeetha, B; Ram, R; Kumar, V S

    2017-01-01

    Bartter's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemia, hypochloremia, metabolic alkalosis, and hyperreninemia with normal blood pressure. Bartter's syndrome is associated with hypercalciuria and nephrocalcinosis. Amelogenesis imperfecta (AI) is a group of hereditary disorders that affect dental enamel. AI could be part of several syndromes. The enamel renal syndrome is the association of AI and nephrocalcinosis. We report two patients of AI with Bartter's syndrome.

  6. Association of amelogenesis imperfecta and Bartter's syndrome

    Directory of Open Access Journals (Sweden)

    A. C. V. Kumar

    2017-01-01

    Full Text Available Bartter's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemia, hypochloremia, metabolic alkalosis, and hyperreninemia with normal blood pressure. Bartter's syndrome is associated with hypercalciuria and nephrocalcinosis. Amelogenesis imperfecta (AI is a group of hereditary disorders that affect dental enamel. AI could be part of several syndromes. The enamel renal syndrome is the association of AI and nephrocalcinosis. We report two patients of AI with Bartter's syndrome.

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

    Directory of Open Access Journals (Sweden)

    Gayatri Gundannavar

    2013-01-01

    Full Text Available 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: review of diagnostic findings and treatment concepts.

    Science.gov (United States)

    Sabandal, Martin M I; Schäfer, Edgar

    2016-09-01

    Mineralization defects like amelogenesis imperfecta are often of hereditary origin. This article reviews the diagnostic findings and summarizes the suggested treatment approaches. Currently, there are no defined therapy recommendations available for patients suffering from amelogenesis imperfecta. The mentioned therapies are more or less equal but no comprehensive therapy recommendation is evident. When treating patients suffering from amelogenesis imperfecta, a comprehensive therapy of almost every dental discipline has to be considered. The earlier the diagnosis of amelogenesis imperfecta is confirmed, the better the outcome is. Optimal treatment approaches consist of early diagnosis and treatment approach and frequent dental recall appointments to prevent progressive occlusal wear or early destruction by caries. Full-mouth prosthetic treatment seems to be the best treatment option.

  9. Amelogenesis Imperfecta with Coronal Resorption: Report of Three Cases.

    Science.gov (United States)

    Bhatia, Shannu K; Hunter, M Lindsay; Ashley, Paul F

    2015-12-01

    Intracoronal resorption of the permanent dentition in cases of amelogenesis imperfecta (AI) is a rare finding which poses an added complication to the already complex management of this condition. This paper presents three cases of AI associated with delayed eruption of permanent teeth in which asymptomatic intracoronal resorption occurred. CPD/Clinical Relevance: This paper highlights the fact that teeth affected with amelogenesis imperfecta may undergo asymptomatic intracoronal resorption which is only identifiable radiographically.

  10. Amelogenesis imperfecta and the treatment plan - interdisciplinary team approach.

    Science.gov (United States)

    Suchancova, B; Holly, D; Janska, M; Stebel, J; Lysy, J; Thurzo, A; Sasinek, S

    2014-01-01

    Amelogenesis imperfecta is a set of hereditary defects representing mainly the development defects of enamel without the presence of whole-body symptoms. Developmental disorders can manifest a complete absence of enamel, which is caused by improper differentiation of ameloblasts. This article describes the diagnosis and treatment of a patient with amelogenesis imperfecta, as well as the need for interdisciplinary cooperation to achieve the best possible morphological, skeletal, functional and aesthetic rehabilitation of the patients with this diagnosis. Furthermore, the article reviews literature dealing with other anomalies occurring in association with amelogenesis imperfect (Fig. 12, Ref. 20).

  11. Interradicular dentin dysplasia associated with amelogenesis imperfecta with taurodontism or trichodentoosseous syndrome: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Veda Hegde

    2014-01-01

    Full Text Available Amelogenesis imperfecta is a hereditary disorder with diverse clinical presentation, where enamel is the tissue that is primarily affected either quantitatively or qualitatively. Hypomaturation/hypoplastic amelogenesis imperfecta with taurodontism is a rare variant of amelogenesis imperfecta which is often confused with trichodentoosseous syndrome. We report a rare case of hereditary enamel defect with taurodontism associated with interradicular dentin dysplasia.

  12. Interradicular dentin dysplasia associated with amelogenesis imperfecta with taurodontism or trichodentoosseous syndrome: a diagnostic dilemma.

    Science.gov (United States)

    Hegde, Veda; Srikanth, K

    2014-01-01

    Amelogenesis imperfecta is a hereditary disorder with diverse clinical presentation, where enamel is the tissue that is primarily affected either quantitatively or qualitatively. Hypomaturation/hypoplastic amelogenesis imperfecta with taurodontism is a rare variant of amelogenesis imperfecta which is often confused with trichodentoosseous syndrome. We report a rare case of hereditary enamel defect with taurodontism associated with interradicular dentin dysplasia.

  13. Amelogenesis Imperfecta; Genes, Proteins, and Pathways

    Directory of Open Access Journals (Sweden)

    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

  14. Amelogenesis Imperfecta; Genes, Proteins, and Pathways.

    Science.gov (United States)

    Smith, Claire E L; Poulter, James A; Antanaviciute, Agne; Kirkham, Jennifer; Brookes, Steven J; Inglehearn, Chris F; Mighell, Alan J

    2017-01-01

    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 speculate on the

  15. Oral Rehabilitation of a Patient with Amelogenesis Imperfecta

    Science.gov (United States)

    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

  16. Alternative prosthodontic-based treatment of a patient with hypocalcified type Amelogenesis Imperfecta.

    Science.gov (United States)

    Jivanescu, Anca; Miglionico, Antonio; Barua, Souman; Hategan, Simona Ioana

    2017-07-01

    The Amelogenesis Imperfecta is associated with malocclusion and usually requires an interdisciplinary treatment. Due to the patient's refusal of orthodontic treatment, prosthodontics-based treatments alternative was considered and planned. The patient was treated with zirconia-based fixed partial dentures, which resulted in improved occlusion, better oral health, and improved esthetic appearance.

  17. Amelogenesis imperfecta: A challenge to restoring esthetics and function

    Directory of Open Access Journals (Sweden)

    Ranganath V

    2010-01-01

    Full Text Available Rehabilitation of complicated cases poses difficulty in clinical practice, both with respect to restoring function and with esthetics. One such clinical condition where the dentist has to give importance to proper planning of the treatment and execution of the plan is amelogenesis imperfecta (AI, a condition where both function and esthetics are accommodated. This article discusses both the functional and esthetic rehabilitation of a patient with AI. Both the esthetics and function were hampered in this patient due to the condition. As a result, the treatment was properly planned and executed. A number of treatment options are available for us today to treat such a case. There is no one technique to be followed as such. However, the aim was to properly diagnose the case and provide good function and esthetics to the patient.

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

    OpenAIRE

    Ping Qing; Yue Li; Shanshan Gao; Mengting Qiao; Linmao Qian; Haiyang Yu

    2015-01-01

    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...

  19. Amelogenesis imperfecta and anterior open bite: Etiological, classification, clinical and management interrelationships.

    Science.gov (United States)

    Alachioti, Xanthippi Sofia; Dimopoulou, Eleni; Vlasakidou, Anatoli; Athanasiou, Athanasios E

    2014-01-01

    Although amelogenesis imperfecta is not a common dental pathological condition, its etiological, classification, clinical and management aspects have been addressed extensively in the scientific literature. Of special clinical consideration is the frequent co-existence of amelogenesis imperfecta with the anterior open bite. This paper provides an updated review on amelogenesis imperfecta as well as anterior open bite, in general, and documents the association of these two separate entities, in particular. Diagnosis and treatment of amelogenesis imperfecta patients presenting also with anterior open bite require a lengthy, comprehensive and multidisciplinary approach, which should aim to successfully address all dental, occlusal, developmental, skeletal and soft tissue problems associated with these two serious clinical conditions.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Noninvasive esthetic treatment for hypomaturation amelogenesis imperfecta: a case report.

    Science.gov (United States)

    Nahsan, Flávia Pardo Salata; Silva, Luciana Mendonça da; Lima, Thiago Mendes de; Bertocco, Verônica Pereira de Lima; Chui, Fabíola Mendonça da Silva; Martins, Leandro de Moura

    2016-01-01

    Enamel alterations, such as amelogenesis imperfecta, can compromise the harmony of the smile and the patient's self-esteem and may cause tooth sensitivity. A simple and effective treatment approach uses the natural stratification of composite resins to mask deficient enamel formation and mimic the natural appearance of the substrate. The operative steps and principles for restorative success are described in this case report with 36-month follow-up.

  2. Amelogenesis Imperfecta - An account of Three Generations affected in a Family

    Directory of Open Access Journals (Sweden)

    G Sarat

    2004-01-01

    Full Text Available Amelogenesis Imperfecta is a hereditary condition affecting dental enamel without any systemic manifestation. This condition can be inherited as either Autosomal or X-linked. In this case report, we discuss with the help of Pedigree Analysis, an account of three generations in a family affected by Autosomal Dominant, Hypoplastic type of Amelogenesis Imperfecta.

  3. Novel FAM20A mutation causes autosomal recessive amelogenesis imperfecta.

    Science.gov (United States)

    Volodarsky, Michael; Zilberman, Uri; Birk, Ohad S

    2015-06-01

    To relate the peculiar phenotype of amelogenesis imperfecta in a large Bedouin family to the genotype determined by whole genome linkage analysis. Amelogenesis imperfecta (AI) is a broad group of inherited pathologies affecting enamel formation, characterized by variability in phenotypes, causing mutations and modes of inheritance. Autosomal recessive or compound heterozygous mutations in FAM20A, encoding sequence similarity 20, member A, have been shown to cause several AI phenotypes. Five members from a large consanguineous Bedouin family presented with hypoplastic amelogenesis imperfecta with unerupted and resorbed permanent molars. Following Soroka Medical Center IRB approval and informed consent, blood samples were obtained from six affected offspring, five obligatory carriers and two unaffected siblings. Whole genome linkage analysis was performed followed by Sanger sequencing of FAM20A. The sequencing unravelled a novel homozygous deletion mutation in exon 11 (c.1523delC), predicted to insert a premature stop codon (p.Thr508Lysfs*6). We provide an interesting case of novel mutation in this rare disorder, in which the affected kindred is unique in the large number of family members sharing a similar phenotype. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. A multidisciplinary approach for the diagnosis of hypocalcified amelogenesis imperfecta in two Chilean families.

    Science.gov (United States)

    Urzúa, Blanca; Ortega-Pinto, Ana; Farias, Daniela Adorno; Franco, Eugenia; Morales-Bozo, Irene; Moncada, Gustavo; Escobar-Pezoa, Nicolás; Scholz, Ursula; Cifuentes, Victor

    2012-01-01

    The purpose of this study was to conduct a multidisciplinary analysis of a specific type of tooth enamel disturbance (amelogenesis imperfecta) affecting two Chilean families to obtain a precise diagnosis and to investigate possible underlying mutations. Two non-related families affected with amelogenesis imperfecta were evaluated with clinical, radiographic and histopathological methods. Furthermore, pedigrees of both families were constructed and the presence of eight mutations in the enamelin gene (ENAM) and three mutations in the enamelysin gene (MMP-20) were investigated by PCR and direct sequencing. In the two affected patients, the dental malformation presented as soft and easily disintegrated enamel and exposed dark dentin. Neither of the affected individuals presented with a dental and skeletal open bite. Histologically, a high level of an organic matrix with prismatic organization was found. Genetic analysis indicated that the condition is autosomal recessive in one family and either autosomal recessive or due to a new mutation in the other family. Molecular mutational analysis revealed that none of the eight mutations previously described in the ENAM gene or the three mutations in the MMP-20 gene were present in the probands. A multidisciplinary analysis allowed for a diagnosis of hypocalcified amelogenesis imperfecta, Witkop type III, which was unrelated to previously described mutations in the ENAM or MMP-20 genes.

  5. Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta.

    Science.gov (United States)

    Poulter, James A; Murillo, Gina; Brookes, Steven J; Smith, Claire E L; Parry, David A; Silva, Sandra; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2014-10-15

    Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is the second most abundant enamel matrix protein expressed during amelogenesis. The pivotal role of AMBN in amelogenesis has been confirmed experimentally using mouse models. However, no AMBN mutations have been associated with human AI. Using autozygosity mapping and exome sequencing, we identified genomic deletion of AMBN exon 6 in a second cousin consanguineous family with three of the six children having hypoplastic AI. The genomic deletion corresponds to an in-frame deletion of 79 amino acids, shortening the protein from 447 to 368 residues. Exfoliated primary teeth (unmatched to genotype) were available from family members. The most severely affected had thin, aprismatic enamel (similar to that reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth exhibited thicker but largely aprismatic enamel. One tooth had apparently normal enamel. It has been suggested that AMBN may function in bone development. No clinically obvious bone or other co-segregating health problems were identified in the family investigated. This study confirms for the first time that AMBN mutations cause non-syndromic human AI and that mouse models with disrupted Ambn function are valid. © The Author 2014. Published by Oxford University Press.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. A syndrome of epilepsy, dementia, and amelogenesis imperfecta: genetic and clinical features.

    OpenAIRE

    Christodoulou, J; Hall, R K; Menahem, S; Hopkins, I J; Rogers, J G

    1988-01-01

    A family is described with six members affected by a syndrome of epilepsy, dementia, and amelogenesis imperfecta (Kohlschütter's syndrome). An autosomal recessive pattern of inheritance is established for this disorder.

  8. Aesthetic composite veneers for an adult patient with amelogenesis imperfecta: a case report.

    Science.gov (United States)

    Brignall, Ian; Mehta, Shamir B; Banerji, Subir; Millar, Brian J

    2011-11-01

    This case has been presented as part of the continual assessment requirement for the MSc in Aesthetic Dentistry, King's College Dental Institute. Amelogenesis imperfecta (AI) is a hereditary disorder of enamel formation, affecting both the permanent and deciduous dentitions. It can be classified into hypoplastic, hypomaturation and hypocalcified types and presents with different hereditary patterns. The aim of this article is to provide an overview of amelogenesis imperfecta, including a detailed case report for an aesthetically concerned adult patient presenting in general practice with a Witkop's Type IA defect managed with the placement of direct, layered resin composite veneers. Amelogenesis imperfecta patients are susceptible to the restorative cycle of replacement restorations like any other patient, but start with a distinct disadvantage.This case report demonstrates a minimally invasive, relatively simple and cost-effective option for the aesthetic correction of a case of hypoplastic amelogenesis imperfecta with layered composite veneers. Dent Update 2011; 38:594-603

  9. Oral Rehabilitation of Young Adult with Amelogenesis Imperfecta.

    Science.gov (United States)

    Leung, Vincent Ws; Low, Bernard; Yang, Yanqi; Botelho, Michael G

    2018-05-01

    Amelogenesis imperfecta is a heterogeneous group of hereditary disorders that affect the enamel formation of the primary and permanent dentitions while the remaining tooth structure is normal. Appropriate patient care is necessary to prevent adverse effects on dental oral health, dental disfigurement, and psychological well-being. This clinical report presents a 27-year-old Chinese male with amelogenesis imperfecta (AI) and his restorative management. This clinical report presents a 27-year-old Chinese male with AI and his restorative management. Extraoral examination showed a skeletal class III profile and increased lower facial proportion. Intraorally, all the permanent dentition was hypoplastic with noticeable tooth surface loss and a yellow-brown appearance. This was complicated with a mild maloc-clusion and food packing on his posterior teeth. The patient wanted to improve his appearance and masticatory efficiency. Orthodontic treatment was performed to treat the mild malocclu-sion and create physiological interproximal spacing to minimize tooth preparation and facilitate oral hygiene. This report demonstrates how a multidisciplinary approach for the management of AI can achieve a predictable, functional, and esthetic outcome. Orthodontic treatment facilitated a conservative prosthodontic treatment outcome by selectively increasing interproximal space, minimizing tooth preparation, correcting posterior bilateral cross-bite, as well as an anterior reverse overjet and derotation of the canines. This case report demonstrates the effective restoration of AI using a multidisciplinary approach to overcome crowding using a relatively conservative approach.

  10. Assessment of restorative treatment of patients with amelogenesis imperfecta.

    Science.gov (United States)

    Chen, Chiung-Fen; Hu, Jan Ching Chun; Estrella, Maria Regina Padilla; Peters, Mathilde C; Bresciani, Eduardo

    2013-01-01

    The purpose of this study was to assess restorative treatment outcomes in the mixed dentition of amelogenesis imperfecta (AI) patients and determine the postrehabilitation oral health status and satisfaction of the patients. Clinical and radiographic examinations were performed on eight AI patients, who had 74 restorations placed in permanent incisors and molars, to allow evaluation of the integrity of the restorations and periodontal status post-treatment. Subjects completed a survey regarding esthetics, function, and sensitivity. Among the 74 restorations evaluated, seven were lost; of the remaining restorations, 31 were posterior, and 36 were anterior. Ten were rated clinically unacceptable. Teeth with stainless steel crowns had a moderate gingival index (mean=2.3) and plaque index (mean=2.0) scores. Widening of the periodontal ligament and pulp canal obliteration were common radiographic findings. Subject's recall of satisfaction regarding esthetics (P=.002) and sensitivity (brushing-P=.03; eating-P=.01) showed a statically significant difference before and after treatment. During mixed dentition, teeth with amelogenesis imperfecta may be restored with conventional treatment modalities. Direct restorations should be considered "interim" with multiple repairs anticipated. Post-treatment, gingival inflammation and plaque accumulation were observed. Subjects were satisfied with their appearance and reported a decrease of hypersensitivity.

  11. Occurrence of epidermolysis bullosa along with Amelogenesis imperfecta in female patient of India

    Directory of Open Access Journals (Sweden)

    A P Javed

    2013-01-01

    Full Text Available Epidermolysis bullosa (EB is an inherited disorder, which is characteristically presented as skin blisters developing in response to minor injury. Junctional variety of EB is also associated with enamel hypoplasia. Amelogenesis imperfecta presents with abnormal formation of the enamel both in deciduous and permanent dentition. This article describes a previously unreported case of Amelogenesis imperfecta with complete loss of enamel in a young female patient with EB.

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

    Science.gov (United States)

    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.

  13. Exonal deletion of SLC24A4 causes hypomaturation amelogenesis imperfecta.

    Science.gov (United States)

    Seymen, F; Lee, K-E; Tran Le, C G; Yildirim, M; Gencay, K; Lee, Z H; Kim, J-W

    2014-04-01

    Amelogenesis imperfecta is a heterogeneous group of genetic conditions affecting enamel formation. Recently, mutations in solute carrier family 24 member 4 (SLC24A4) have been identified to cause autosomal recessive hypomaturation amelogenesis imperfecta. We recruited a consanguineous family with hypomaturation amelogenesis imperfecta with generalized brown discoloration. Sequencing of the candidate genes identified a 10-kb deletion, including exons 15, 16, and most of the last exon of the SLC24A4 gene. Interestingly, this deletion was caused by homologous recombination between two 354-bp-long homologous sequences located in intron 14 and the 3' UTR. This is the first report of exonal deletion in SLC24A4 providing confirmatory evidence that the function of SLC24A4 in calcium transport has a crucial role in the maturation stage of amelogenesis.

  14. Bilateral nephrocalcinosis and amelogenesis imperfecta: A case report

    Directory of Open Access Journals (Sweden)

    Alok Patel

    2015-01-01

    Full Text Available Amelogenesis imperfecta (AI is a group of hereditary disorders that affect the quality and/or quantity of dental enamel. This paper describes the clinicopathological features of a patient who was born of nonconsanguineous parents and who presented with oral alterations, including yellow and misshapen teeth, intrapulpal calcifications, delayed tooth eruption, and gum enlargement. Scanning electron microscopy of the teeth revealed hypoplastic enamel, and a renal ultrasound detected bilateral nephrocalcinosis, leading to a diagnosis of AI and nephrocalcinosis syndrome. Since nephrocalcinosis is often asymptomatic and can be associated with impaired renal function, dentists who see children with a generalized and thin hypoplastic AI should consider a renal ultrasound scan and referral to a Nephrologist. Children with nephrocalcinosis should also be considered for a dental check.

  15. Amelogenesis Imperfecta and Screening of Mutation in Amelogenin Gene

    Directory of Open Access Journals (Sweden)

    Fernanda Veronese Oliveira

    2014-01-01

    Full Text Available The aim of this study was to report the clinical findings and the screening of mutations of amelogenin gene of a 7-year-old boy with amelogenesis imperfecta (AI. The genomic DNA was extracted from saliva of patient and his family, followed by PCR and direct DNA sequencing. The c.261C>T mutation was found in samples of mother, father, and brother, but the mutation was not found in the sequence of the patient. This mutation is a silent mutation and a single-nucleotide polymorphism (rs2106416. Thus, it is suggested that the mutation found was not related to the clinical presence of AI. Further research is necessary to examine larger number of patients and genes related to AI.

  16. Amelogenesis Imperfecta with Distal Renal Tubular Acidosis: A Novel Syndrome?

    Science.gov (United States)

    Misgar, R A; Hassan, Z; Wani, A I; Bashir, M I

    2017-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Amelogenesis Imperfecta: 1 Family, 2 Phenotypes, and 2 Mutated Genes.

    Science.gov (United States)

    Prasad, M K; Laouina, S; El Alloussi, M; Dollfus, H; Bloch-Zupan, A

    2016-12-01

    Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of diseases characterized by enamel defects. The authors have identified a large consanguineous Moroccan family segregating different clinical subtypes of hypoplastic and hypomineralized AI in different individuals within the family. Using targeted next-generation sequencing, the authors identified a novel heterozygous nonsense mutation in COL17A1 (c.1873C>T, p.R625*) segregating with hypoplastic AI and a novel homozygous 8-bp deletion in C4orf26 (c.39_46del, p.Cys14Glyfs*18) segregating with hypomineralized-hypoplastic AI in this family. This study highlights the phenotypic and genotypic heterogeneity of AI that can exist even within a single consanguineous family. Furthermore, the identification of novel mutations in COL17A1 and C4orf26 and their correlation with distinct AI phenotypes can contribute to a better understanding of the pathophysiology of AI and the contribution of these genes to amelogenesis. © International & American Associations for Dental Research 2016.

  19. Enamelin/ameloblastin gene polymorphisms in autosomal amelogenesis imperfecta among Syrian families.

    Science.gov (United States)

    Dashash, Mayssoon; Bazrafshani, Mohamed Riza; Poulton, Kay; Jaber, Saaed; Naeem, Emad; Blinkhorn, Anthony Stevenson

    2011-02-01

      This study was undertaken to investigate whether a single G deletion within a series of seven G residues (codon 196) at the exon 9-intron 9 boundary of the enamelin gene ENAM and a tri-nucleotide deletion at codon 180 in exon 7 (GGA vs deletion) of ameloblastin gene AMBN could have a role in autosomal amelogenesis imperfecta among affected Syrian families.   A new technique - size-dependent, deletion screening - was developed to detect nucleotide deletion in ENAM and AMBN genes. Twelve Syrian families with autosomal-dominant or -recessive amelogenesis imperfecta were included.   A homozygous/heterozygous mutation in the ENAM gene (152/152, 152/153) was identified in affected members of three families with autosomal-dominant amelogenesis imperfecta and one family with autosomal-recessive amelogenesis imperfecta. A heterozygous mutation (222/225) in the AMBN gene was identified. However, no disease causing mutations was found. The present findings provide useful information for the implication of ENAM gene polymorphism in autosomal-dominant/-recessive amelogenesis imperfecta.   Further investigations are required to identify other genes responsible for the various clinical phenotypes. © 2010 Blackwell Publishing Asia Pty Ltd.

  20. A rare association--amelogenesis imperfecta, platispondyly and bicytopenia: a case report.

    Science.gov (United States)

    Laouina, Samir; El Alaoui, Siham Chafai; Amezian, Rachida; Al Bouzidi, Abderrahmane; Sefiani, Abdelaziz; El Alloussi, Mustapha

    2015-10-28

    Amelogenesis imperfecta is an inherited disease characterized by generalized structural abnormalities of the enamel on all teeth, including both primary and permanent dentition. To the best of our knowledge, this is the first case report of a rare association of amelogenesis imperfecta, platyspondyly, and bicytopenia. A 5-year-old Moroccan boy was examined in the Centre for Dental Consultation and Treatment, Faculty of Dentistry, Rabat. He was a child of consanguineous parents (first degree). The child failed to thrive (-4 standard deviation score) and displayed delayed overall development. A dental examination revealed a hypoplastic amelogenesis imperfecta with a bacterial biofilm deposit on tooth surfaces. A complete blood count revealed bicytopenia (normocytic-normochromic anemia with thrombocytopenia). A radiographic examination of the spinal column showed a deviation of the spine in the frontal plane in the form of thoracolumbar scoliosis. The interpedicular distance was not expanded; but a mild platyspondyly exists, especially pronounced in T11 and T12. No other family members presented amelogenesis imperfecta, bicytopenia, or platyspondyly. The consanguineous marriage suggested an autosomal recessive mode of inheritance. Further studies are necessary to clarify the genetic defect producing this syndrome, and the symptomatic associations of amelogenesis imperfecta, platyspondyly and bicytopenia.

  1. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali

    2015-09-01

    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.

  4. Amelogenesis Imperfecta with Taurodontism, Microdontia, and Minor Thalassemia: A Case Report

    Directory of Open Access Journals (Sweden)

    Fatemeh Mazhari

    2013-12-01

    Full Text Available Amelogenesis imperfecta is a group of genetic disorders that affects both the morphology and quality of tooth structure. Although the disease entity is primarily associated with abnormalities of dental and oral structures, it has been reported to be associated with a few syndromes. A 9-year-old girl with minor thalassemia referred to the Department of Pediatric Dentistry of the Mashhad Faculty of Dentistry with a complaint of sensitivity of first permanent molars. Dental findings consisted of amelogenesis imperfecta, microdontia, posterior cross bite and taurodontism. This is the first report of thalassemia accompanied with amelogenesis imperfecta. Although the patients often are non-symptomatic, the trait can be passed on to a child and if both parents carry the trait, the child could develop a more severe form of the disease; therefore, early diagnosis is important.

  5. Diagnosis, treatment planning, and full-mouth rehabilitation in a case of amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Mayuri Naik

    2018-01-01

    Full Text Available Amelogenesis imperfecta is a genetic condition affecting the teeth resulting in aberrations of the structure and clinical appearance of enamel. The treatment of amelogenesis imperfecta involves a multidisciplinary treatment approach requiring a comprehensive examination, diagnosis, and effective treatment planning strategy along with satisfaction of patient-related factors. The clinical case described here involves judicious involvement of different disciplines to formulate a treatment plan best suitable to confirm with the patient's needs and expectations, at the same time maintaining the integrity and harmony of associated hard and soft tissues.

  6. Microtensile bond strength to enamel affected by hypoplastic amelogenesis imperfecta.

    Science.gov (United States)

    Yaman, Batu Can; Ozer, Fusun; Cabukusta, Cigdem Sozen; Eren, Meltem M; Koray, Fatma; Blatz, Markus B

    2014-02-01

    This study compared the microtensile bond strengths (μTBS) of two different self-etching (SE) and etchand- rinse (ER) adhesive systems to enamel affected by hypoplastic amelogenesis imperfecta (HPAI) and analyzed the enamel etching patterns created by the two adhesive systems using scanning electron microscopy (SEM). Sixteen extracted HPAI-affected molars were used for the bond strength tests and 2 molars were examined under SEM for etching patterns. The control groups consisted of 12 healthy third molars for μTBS tests and two molars for SEM. Mesial and distal surfaces of the teeth were slightly ground flat. The adhesive systems and composite resin were applied to the flat enamel surfaces according to the manufacturers' instructions. The tooth slabs containing composite resin material on their mesial and distal surfaces were cut in the mesio-distal direction with a slow-speed diamond saw. The slabs were cut again to obtain square, 1-mm-thick sticks. Finally, each stick was divided into halves and placed in the μTBS tester. Bond strength tests were performed at a speed of 0.5 mm/min. Data were analyzed with two-way ANOVA and Tukey's tests. There was no significant difference between the bond strength values of ER and SE adhesives (p > 0.05). However, significant differences were found between HPAI and control groups (p systems provide similar bond strengths to HPAI-affected enamel surfaces.

  7. Novel ITGB6 mutation in autosomal recessive amelogenesis imperfecta.

    Science.gov (United States)

    Seymen, F; Lee, K-E; Koruyucu, M; Gencay, K; Bayram, M; Tuna, E B; Lee, Z H; Kim, J-W

    2015-05-01

    Hereditary defects in tooth enamel formation, amelogenesis imperfecta (AI), can be non-syndromic or syndromic phenotype. Integrins are signaling proteins that mediate cell-cell and cell-extracellular matrix communication, and their involvement in tooth development is well known. The purposes of this study were to identify genetic cause of an AI family and molecular pathogenesis underlying defective enamel formation. We recruited a Turkish family with isolated AI and performed mutational analyses to clarify the underlying molecular genetic etiology. Autozygosity mapping and exome sequencing identified a novel homozygous ITGB6 transversion mutation in exon 4 (c.517G>C, p.Gly173Arg). The glycine at this position in the middle of the βI-domain is conserved among a wide range of vertebrate orthologs and human paralogs. Clinically, the enamel was generally thin and pitted with pigmentation. Thicker enamel was noted at the cervical area of the molars. In this study, we identified a novel homozygous ITGB6 mutation causing isolated AI, and this advances the understanding of normal and pathologic enamel development. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. A novel AMELX mutation causes hypoplastic amelogenesis imperfecta.

    Science.gov (United States)

    Kim, Young-Jae; Kim, Youn Jung; Kang, Jenny; Shin, Teo Jeon; Hyun, Hong-Keun; Lee, Sang-Hoon; Lee, Zang Hee; Kim, Jung-Wook

    2017-04-01

    Amelogenesis imperfecta (AI) is a hereditary genetic defect affecting tooth enamel. AI is heterogeneous in clinical phenotype as well as in genetic etiology. To date, more than 10 genes have been associated with the etiology of AI. Amelogenin is the most abundant enamel matrix protein, most of which is encoded by the amelogenin gene in the X-chromosome (AMELX). More than 16 alternative splicing transcripts have been identified in the murine Amelx gene. The purpose of this study was to identify the genetic cause of an AI family. We recruited a family with hypoplastic AI and performed mutational analysis on the candidate gene based on the clinical phenotype. Mutational analysis revealed a missense mutation in exon 6 (NM_182680.1; c.242C > T), which changes a sequence in a highly conserved amino acid (NP_872621.1; p.Pro81Leu). Furthermore, a splicing assay using a minigene displayed that the mutation changed the mRNA splicing repertory. In this study, we identified a novel AMELX missense mutation causing hypoplastic AI, and this mutation also resulted in altered mRNA splicing. These results will not only expand the mutation spectrum causing AI but also broaden our understanding of the biological mechanism of enamel formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Target gene analyses of 39 amelogenesis imperfecta kindreds

    Science.gov (United States)

    Chan, Hui-Chen; Estrella, Ninna M. R. P.; Milkovich, Rachel N.; Kim, Jung-Wook; Simmer, James P.; Hu, Jan C-C.

    2012-01-01

    Previously, mutational analyses identified six disease-causing mutations in 24 amelogenesis imperfecta (AI) kindreds. We have since expanded the number of AI kindreds to 39, and performed mutation analyses covering the coding exons and adjoining intron sequences for the six proven AI candidate genes [amelogenin (AMELX), enamelin (ENAM), family with sequence similarity 83, member H (FAM83H), WD repeat containing domain 72 (WDR72), enamelysin (MMP20), and kallikrein-related peptidase 4 (KLK4)] and for ameloblastin (AMBN) (a suspected candidate gene). All four of the X-linked AI families (100%) had disease-causing mutations in AMELX, suggesting that AMELX is the only gene involved in the aetiology of X-linked AI. Eighteen families showed an autosomal-dominant pattern of inheritance. Disease-causing mutations were identified in 12 (67%): eight in FAM83H, and four in ENAM. No FAM83H coding-region or splice-junction mutations were identified in three probands with autosomal-dominant hypocalcification AI (ADHCAI), suggesting that a second gene may contribute to the aetiology of ADHCAI. Six families showed an autosomal-recessive pattern of inheritance, and disease-causing mutations were identified in three (50%): two in MMP20, and one in WDR72. No disease-causing mutations were found in 11 families with only one affected member. We conclude that mutation analyses of the current candidate genes for AI have about a 50% chance of identifying the disease-causing mutation in a given kindred. PMID:22243262

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

    Science.gov (United States)

    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.

  12. Prosthetic and Surgical Approach for Oral Rehabilitation in a Patient with Amelogenesis Imperfecta: A Clinical Report

    Directory of Open Access Journals (Sweden)

    H. Sazegara

    2007-06-01

    Full Text Available Amelogenesis imperfecta is a heterogeneous group of hereditary disorders. Its treatment continues throughout the patients’ childhood and adolescence and consists of advanced restorative care in severe cases.A thorough prosthodontic treatment plan including orthognatic surgery, full veneer crowns and all ceramic anterior crowns is presented in this clinical report.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Dental management of amelogenesis imperfecta patients: a primer on genotype-phenotype correlations.

    Science.gov (United States)

    Ng, F K; Messer, L B

    2009-01-01

    Amelogenesis imperfecta (AI) represents a group of hereditary conditions which affects enamel formation in the primary and permanent dentitions. Mutations in genes critical for amelogenesis result in diverse phenotypes characterized by variably thin and/or defective enamel. To date, mutations in 5 genes are known to cause AI in humans. Understanding the molecular etiologies and associated inheritance patterns can assist in the early diagnosis of this condition. Recognition of genotype-phenotype correlations will allow clinicians to guide genetic testing and select appropriate management strategies for patients who express different phenotypes. The purpose of this paper was to provide a narrative review of the current literature on amelogenesis imperfecta, particularly regarding recent advances in the identification of candidate genes and the patterns of inheritance.

  15. Pre-Eruptive Coronal Resorption and Congenitally Missing Teeth in a Patient with Amelogenesis Imperfecta: A Case Report

    OpenAIRE

    Miloglu, Ozkan; Karaalioglu, Osman Fatih; Caglayan, Fatma; Yesil, Zeynep Duymus

    2009-01-01

    This clinical report describes a male with autosomal recessive generalized hypoplastic amelogenesis imperfecta. This case is unusual in coronal resorptions prior to tooth eruption. This finding has been reported in some cases of autosomal recessive, autosomal dominant and X linked amelogenesis imperfecta (AI). In reported cases, the defects were usually small and occurred in a maximum of 2 teeth per person. In our case, pre-eruptive coronal resorptions affected three second molar teeth from b...

  16. Oral rehabilitation of a patient with amelogenesis imperfecta using removable overlay denture: a clinical report.

    Science.gov (United States)

    Ghodsi, S; Rasaeipour, S; Vojdani, M

    2012-03-01

    The aim of this study was oral rehabilitation of 17-year old patient with amelogenesis imperfecta using removable overlay denture in order to satisfy her esthetic and functional expectations and enhance her self-image. Amelogenesis imperfecta (AI) is a group of genetic disorders that primarily affect the quality and quantity of amelogenesis in both primary and permanent dentitions. The main clinical characteristics are severe attrition, tooth sensitivity and unesthetic appearance. This clinical report illustrates the oral rehabilitation of a 17-year-old girl with hypoplastic-hypomature type of AI with cobalt-chromium (Co-Cr) overlay removable partial denture (ORPD) that is one of the most economical and biocompatible replacements for noble metal and nickel-chromium (Ni-Cr) alloy. The presented case report suggests that Co-Cr ORPD can be a good temporary or even permanent treatment option for AI patients with limited budget, low esthetic concerns or medical limitations. There are major advantages in cast metal ORPDs; they are simpler, less traumatic and less expensive than fixed prosthetic options. This case report supports their use in patients with amelogenesis imperfecta.

  17. Missense Mutation in Fam83H Gene in Iranian Patients with Amelogenesis Imperfecta.

    Science.gov (United States)

    Pourhashemi, S Jalal; Ghandehari Motlagh, Mehdi; Meighani, Ghasem; Ebrahimi Takaloo, Azadeh; Mansouri, Mahsa; Mohandes, Fatemeh; Mirzaii, Maryam; Khoshzaban, Ahad; Moshtaghi, Faranak; Abedkhojasteh, Hoda; Heidari, Mansour

    2014-12-01

    Amelogenesis Imperfecta (AI) is a disorder of tooth development where there is an abnormal formation of enamel or the external layer of teeth. The aim of this study was to screen mutations in the four most important candidate genes, ENAM, KLK4, MMP20 and FAM83H responsible for amelogenesis imperfect. Geneomic DNA was isolated from five Iranian families with 22 members affected with enamel malformations. The PCR amplifications were typically carried out for amplification the coding regions for AI patients and unaffected family members. The PCR products were subjected to direct sequencing. The pedigree analysis was performed using Cyrillic software. One family had four affected members with autosomal dominant hypocalcified amelogenesis imperfecta (ADHPCAI); pedigree analysis revealed four consanguineous families with 18 patients with autosomal recessive hypoplastic amelogenesis imperfecta (ARHPAI). One non-synonymous single-nucleotide substitution, c.1150T>A, p. Ser 342Thr was identified in the FAM83H, which resulted in ADHCAI. Furthermore, different polymorphisms or unclassified variants were detected in MMP20, ENAM and KLK4. Our results are consistent with other studies and provide further evidence for pathogenic mutations of FAM83H gene. These findings suggest different loci and genes could be implicated in the pathogenesis of AI.

  18. Defining a new candidate gene for amelogenesis imperfecta: from molecular genetics to biochemistry.

    Science.gov (United States)

    Urzúa, Blanca; Ortega-Pinto, Ana; Morales-Bozo, Irene; Rojas-Alcayaga, Gonzalo; Cifuentes, Víctor

    2011-02-01

    Amelogenesis imperfecta is a group of genetic conditions that affect the structure and clinical appearance of tooth enamel. The types (hypoplastic, hypocalcified, and hypomature) are correlated with defects in different stages of the process of enamel synthesis. Autosomal dominant, recessive, and X-linked types have been previously described. These disorders are considered clinically and genetically heterogeneous in etiology, involving a variety of genes, such as AMELX, ENAM, DLX3, FAM83H, MMP-20, KLK4, and WDR72. The mutations identified within these causal genes explain less than half of all cases of amelogenesis imperfecta. Most of the candidate and causal genes currently identified encode proteins involved in enamel synthesis. We think it is necessary to refocus the search for candidate genes using biochemical processes. This review provides theoretical evidence that the human SLC4A4 gene (sodium bicarbonate cotransporter) may be a new candidate gene.

  19. 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

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

  20. Analyses of MMP20 Missense Mutations in Two Families with Hypomaturation Amelogenesis Imperfecta.

    Science.gov (United States)

    Kim, Youn Jung; Kang, Jenny; Seymen, Figen; Koruyucu, Mine; Gencay, Koray; Shin, Teo Jeon; Hyun, Hong-Keun; Lee, Zang Hee; Hu, Jan C-C; Simmer, James P; Kim, Jung-Wook

    2017-01-01

    Amelogenesis imperfecta is a group of rare inherited disorders that affect tooth enamel formation, quantitatively and/or qualitatively. The aim of this study was to identify the genetic etiologies of two families presenting with hypomaturation amelogenesis imperfecta. DNA was isolated from peripheral blood samples obtained from participating family members. Whole exome sequencing was performed using DNA samples from the two probands. Sequencing data was aligned to the NCBI human reference genome (NCBI build 37.2, hg19) and sequence variations were annotated with the dbSNP build 138. Mutations in MMP20 were identified in both probands. A homozygous missense mutation (c.678T>A; p.His226Gln) was identified in the consanguineous Family 1. Compound heterozygous MMP20 mutations (c.540T>A, p.Tyr180 * and c.389C>T, p.Thr130Ile) were identified in the non-consanguineous Family 2. Affected persons in Family 1 showed hypomaturation AI with dark brown discoloration, which is similar to the clinical phenotype in a previous report with the same mutation. However, the dentition of the Family 2 proband exhibited slight yellowish discoloration with reduced transparency. Functional analysis showed that the p.Thr130Ile mutant protein had reduced activity of MMP20, while there was no functional MMP20 in the Family 1 proband. These results expand the mutational spectrum of the MMP20 and broaden our understanding of genotype-phenotype correlations in amelogenesis imperfecta.

  1. Analyses of MMP20 Missense Mutations in Two Families with Hypomaturation Amelogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Jung-Wook Kim

    2017-04-01

    Full Text Available Amelogenesis imperfecta is a group of rare inherited disorders that affect tooth enamel formation, quantitatively and/or qualitatively. The aim of this study was to identify the genetic etiologies of two families presenting with hypomaturation amelogenesis imperfecta. DNA was isolated from peripheral blood samples obtained from participating family members. Whole exome sequencing was performed using DNA samples from the two probands. Sequencing data was aligned to the NCBI human reference genome (NCBI build 37.2, hg19 and sequence variations were annotated with the dbSNP build 138. Mutations in MMP20 were identified in both probands. A homozygous missense mutation (c.678T>A; p.His226Gln was identified in the consanguineous Family 1. Compound heterozygous MMP20 mutations (c.540T>A, p.Tyr180* and c.389C>T, p.Thr130Ile were identified in the non-consanguineous Family 2. Affected persons in Family 1 showed hypomaturation AI with dark brown discoloration, which is similar to the clinical phenotype in a previous report with the same mutation. However, the dentition of the Family 2 proband exhibited slight yellowish discoloration with reduced transparency. Functional analysis showed that the p.Thr130Ile mutant protein had reduced activity of MMP20, while there was no functional MMP20 in the Family 1 proband. These results expand the mutational spectrum of the MMP20 and broaden our understanding of genotype-phenotype correlations in amelogenesis imperfecta.

  2. Further evidence for causal FAM20A mutations and first case of amelogenesis imperfecta and gingival hyperplasia syndrome in Morocco: a case report.

    Science.gov (United States)

    Cherkaoui Jaouad, Imane; El Alloussi, Mustapha; Chafai El Alaoui, Siham; Laarabi, Fatima Zahra; Lyahyai, Jaber; Sefiani, Abdelaziz

    2015-01-30

    Amelogenesis imperfecta represents a group of developmental conditions, clinically and genetically heterogeneous, that affect the structure and clinical appearance of enamel. Amelogenesis imperfecta occurred as an isolated trait or as part of a genetic syndrome. Recently, disease-causing mutations in the FAM20A gene were identified, in families with an autosomal recessive syndrome associating amelogenesis imperfecta and gingival fibromatosis. We report, the first description of a Moroccan patient with amelogenesis imperfecta and gingival fibromatosis, in whom we performed Sanger sequencing of the entire coding sequence of FAM20A and identified a homozygous mutation in the FAM20A gene (c.34_35delCT), already reported in a family with this syndrome. Our finding confirms that the mutations of FAM20A gene are causative for amelogenesis imperfecta and gingival fibromatosis and underlines the recurrent character of the c.34_35delCT in two different ethnic groups.

  3. Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression.

    Science.gov (United States)

    Xie, Xiaohua; Liu, Chao; Zhang, Hua; Jani, Priyam H; Lu, Yongbo; Wang, Xiaofang; Zhang, Bin; Qin, Chunlin

    2016-05-05

    Amelogenesis Imperfecta (AI) can be caused by the deficiencies of enamel matrix proteins, molecules responsible for the transportation and secretion of enamel matrix components, and proteases processing enamel matrix proteins. In the present study, we discovered the double deletion of bone morphogenetic protein 2 (Bmp2) and bone morphogenetic protein 4 (Bmp4) in the dental epithelium by K14-cre resulted in hypoplastic enamel and reduced density in X-ray radiography as well as shortened enamel rods under scanning electron microscopy. Such enamel phenotype was consistent with the diagnosis of hypoplastic amelogenesis imperfecta. Histological and molecular analyses revealed that the removal of matrix proteins in the mutant enamel was drastically delayed, which was coincided with the greatly reduced expression of matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4). Although the expression of multiple enamel matrix proteins was down-regulated in the mutant ameloblasts, the cleavage of ameloblastin was drastically impaired. Therefore, we attributed the AI primarily to the reduction of MMP20 and KLK4. Further investigation found that BMP/Smad4 signaling pathway was down-regulated in the K14-cre;Bmp2(f/f);Bmp4(f/f)ameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling.

  4. Isolation and characterization of dental epithelial cells derived from amelogenesis imperfecta rat.

    Science.gov (United States)

    Adiningrat, A; Tanimura, A; Miyoshi, K; Hagita, H; Yanuaryska, R D; Arinawati, D Y; Horiguchi, T; Noma, T

    2016-03-01

    Disruption of the third zinc finger domain of specificity protein 6 (SP6) presents an enamel-specific defect in a rat model of amelogenesis imperfecta (AMI rats). To understand the molecular basis of amelogenesis imperfecta caused by the Sp6 mutation, we established and characterized AMI-derived rat dental epithelial (ARE) cells. ARE cell clones were isolated from the mandibular incisors of AMI rats, and amelogenesis-related gene expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Localization of wild-type SP6 (SP6WT) and mutant-type SP6 (SP6AMI) was analyzed by immunocytochemistry. SP6 transcriptional activity was monitored by rho-associated protein kinase 1 (Rock1) promoter activity with its specific binding to the promoter region in dental (G5 and ARE) and non-dental (COS-7) epithelial cells. Isolated ARE cells were varied in morphology and gene expression. Both SP6WT and SP6AMI were mainly detected in nuclei. The promoter analysis revealed that SP6WT and SP6AMI enhanced Rock1 promoter activity in G5 cells but that enhancement by SP6AMI was weaker, whereas no enhancement was observed in the ARE and COS-7 cells, even though SP6WT and SP6AMI bound to the promoter in all instances. ARE cell clones can provide a useful in vitro model to study the mechanism of SP6-mediated amelogenesis imperfecta. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Typical Features of Amelogenesis Imperfecta in Two Patients with Bartter’s Syndrome

    Directory of Open Access Journals (Sweden)

    Hercílio Martelli-Júnior

    2012-12-01

    Full Text Available Background/Aims: Amelogenesis imperfecta (AI is due to many inherited defects of enamel formation that affect the quantity and quality of enamel, leading to delay in tooth eruption and cosmetic consequences. AI has been described in association with nephrocalcinosis, which is called the enamel-renal syndrome. The aim of this case report is to describe typical features of AI in 2 patients with Bartter’s syndrome (BS for the first time. Methods: -Eight patients with confirmed BS were systematically screened for dental abnormalities as part of protocol. Those with suggestive clinical features of AI were submitted to panoramic X-ray and decayed teeth were analyzed by scanning electron microscopy. Results: Typical features of AI were detected in 2 girls with BS. These 2 patients showed nephrocalcinosis, and diagnosis and adequate clinical control were delayed. Genetic analysis detected the mutation responsible for BS in 1 of these patients. In this case, BS was due to a homozygous mutation of exon 5 of the KCNJ1 gene resulting in a substitution of valine for alanine at the codon 214 (A214V. Conclusions: The finding of typical features of AI in BS might constitute preliminary evidence that abnormalities of the biomineralization process found in patients with renal tubular disorders might also affect calcium deposition in dental tissues.

  6. Endoplasmic reticulum stress in amelogenesis imperfecta and phenotypic rescue using 4-phenylbutyrate.

    Science.gov (United States)

    Brookes, Steven J; Barron, Martin J; Boot-Handford, Ray; Kirkham, Jennifer; Dixon, Michael J

    2014-05-01

    Inherited diseases caused by genetic mutations can arise due to loss of protein function. Alternatively, mutated proteins may mis-fold, impairing endoplasmic reticulum (ER) trafficking, causing ER stress and triggering the unfolded protein response (UPR). The UPR attempts to restore proteostasis but if unsuccessful drives affected cells towards apoptosis. Previously, we reported that in mice, the p.Tyr64His mutation in the enamel extracellular matrix (EEM) protein amelogenin disrupts the secretory pathway in the enamel-forming ameloblasts, resulting in eruption of malformed tooth enamel that phenocopies human amelogenesis imperfecta (AI). Defective amelogenin post-secretory self-assembly and processing within the developing EEM has been suggested to underlie the pathogenesis of X chromosome-linked AI. Here, we challenge this concept by showing that AI pathogenesis associated with the p.Tyr64His amelogenin mutation involves ameloblast apoptosis induced by ER stress. Furthermore, we show that 4-phenylbutyrate can rescue the enamel phenotype in affected female mice by promoting cell survival over apoptosis such that they are able to complete enamel formation despite the presence of the mutation, offering a potential therapeutic option for patients with this form of AI and emphasizing the importance of ER stress in the pathogenesis of this inherited conformational disease.

  7. Amelogenesis Imperfecta: Rehabilitation and Brainstorming on the Treatment Outcome after the First Year

    Directory of Open Access Journals (Sweden)

    Ayça Deniz İzgi

    2015-01-01

    Full Text Available Amelogenesis imperfecta (AI affects enamel on primary and permanent dentition. This hereditary disorder is characterized by loss of enamel, poor esthetics, and hypersensitivity. Functional and cosmetic rehabilitation is challenging with variety of treatment options. This report presents the treatment of an AI patient using conventional fixed dentures and discusses issues related to posttreatment complications and prosthetic treatment outcome after 1 year of follow-up. A 19-year-old male AI patient with impaired self-esteem presented with hypersensitive, discolored, and mutilated teeth. Clinical examination revealed compromised occlusion and anterior open-bite. After hygiene maintenance full-coverage porcelain-fused-to-metal fixed restorations were indicated and applied. At the end of the treatment acceptable functional and esthetic results could be achieved. However, nearly a year after treatment a gingival inflammation in the esthetic zone complicated the outcome. Insufficient oral hygiene was to be blamed. Tooth sensitivity present from early childhood in these patients may prevent oral hygiene from becoming a habit. The relaxation due to relieve of hypersensitivity after treatment makes oral hygiene learning difficult. Continuous oral hygiene maintenance motivation may be crucial for the success of the treatment of AI patients. Treatment of AI patients should be carefully planned and an acceptable risk-benefit balance should be established.

  8. Recessive Mutations in ACPT, Encoding Testicular Acid Phosphatase, Cause Hypoplastic Amelogenesis Imperfecta.

    Science.gov (United States)

    Seymen, Figen; Kim, Youn Jung; Lee, Ye Ji; Kang, Jenny; Kim, Tak-Heun; Choi, Hwajung; Koruyucu, Mine; Kasimoglu, Yelda; Tuna, Elif Bahar; Gencay, Koray; Shin, Teo Jeon; Hyun, Hong-Keun; Kim, Young-Jae; Lee, Sang-Hoon; Lee, Zang Hee; Zhang, Hong; Hu, Jan C-C; Simmer, James P; Cho, Eui-Sic; Kim, Jung-Wook

    2016-11-03

    Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders affecting tooth enamel. The affected enamel can be hypoplastic and/or hypomineralized. In this study, we identified ACPT (testicular acid phosphatase) biallelic mutations causing non-syndromic, generalized hypoplastic autosomal-recessive amelogenesis imperfecta (AI) in individuals from six apparently unrelated Turkish families. Families 1, 4, and 5 were affected by the homozygous ACPT mutation c.713C>T (p.Ser238Leu), family 2 by the homozygous ACPT mutation c.331C>T (p.Arg111Cys), family 3 by the homozygous ACPT mutation c.226C>T (p.Arg76Cys), and family 6 by the compound heterozygous ACPT mutations c.382G>C (p.Ala128Pro) and 397G>A (p.Glu133Lys). Analysis of the ACPT crystal structure suggests that these mutations damaged the activity of ACPT by altering the sizes and charges of key amino acid side chains, limiting accessibility of the catalytic core, and interfering with homodimerization. Immunohistochemical analysis confirmed localization of ACPT in secretory-stage ameloblasts. The study results provide evidence for the crucial function of ACPT during amelogenesis. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. Chairside treatment of amelogenesis imperfecta, including establishment of a new vertical dimension with resin nanoceramic and intraoral scanning.

    Science.gov (United States)

    Zimmermann, Moritz; Koller, Christina; Hickel, Reinhard; Kühnisch, Jan

    2016-09-01

    Amelogenesis imperfecta is a hereditary disease affecting the structural development of tooth substance. This clinical report describes a 1-visit chairside treatment of an 8-year-old patient with amelogenesis imperfecta, using computer-aided design and computer-aided manufacturing (CAD-CAM) technology. Intraoral scanning was performed using the Cerec Omnicam. Thirteen resin nanoceramic crowns (Lava Ultimate) were fabricated chairside by using a Cerec MCXL milling unit and seated adhesively. The patient's treatment included establishing a new occlusal vertical dimension and new centric relationship. Reevaluation after 6 months showed a stable situation. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  10. Literature review of amelogenesis imperfecta with case report

    Directory of Open Access Journals (Sweden)

    Sumathy C Chanmougananda

    2012-01-01

    Full Text Available Amelogenesis impertecta (Al is a diverse collection of inherited diseases that exhibit qualitative or quantitative tooth enamel defects in the absence of systemic manifestations. Also known by varied names, such as hereditary enamel dysplasia, hereditary brown opalescent teeth, this defect is entirely ectodermal, since mesodermal components of the teeth are basically normal. This article details a case of Al along with complete review which presents in his twin siblings with clinical, radiological and histopathological report.

  11. Defects in the acid phosphatase ACPT cause recessive hypoplastic amelogenesis imperfecta.

    Science.gov (United States)

    Smith, Claire El; Whitehouse, Laura LE; Poulter, James A; Brookes, Steven J; Day, Peter F; Soldani, Francesca; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2017-08-01

    We identified two homozygous missense variants (c.428C>T, p.(T143M) and c.746C>T, p.(P249L)) in ACPT, the gene encoding acid phosphatase, testicular, which segregates with hypoplastic amelogenesis imperfecta in two unrelated families. ACPT is reported to play a role in odontoblast differentiation and mineralisation by supplying phosphate during dentine formation. Analysis by computerised tomography and scanning electron microscopy of a primary molar tooth from an individual homozygous for the c.746C>T variant revealed an enamel layer that was hypoplastic, but mineralised with prismatic architecture. These findings implicate variants in ACPT as a cause of early failure of amelogenesis during the secretory phase.

  12. An Interdisciplinary Approach for Rehabilitating a Patient with Amelogenesis Imperfecta: A Case Report

    Directory of Open Access Journals (Sweden)

    Niloufar Khodaeian

    2012-01-01

    Full Text Available Amelogenesis imperfecta (AI has been defined as a group of hereditary enamel defects. It can be characterized by enamel hypoplasia, hypomaturation, or hypocalcification of the teeth. AI may be associated with some other dental and skeletal developmental defects. Restoration for patients with this condition should be oriented toward the functional and esthetic rehabilitation. This clinical report describes the oral rehabilitation of a young patient diagnosed with the hypoplastic type of AI in posterior teeth and hypomatured type of AI in anterior teeth.

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

    Science.gov (United States)

    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.

  14. The absence of correlations between a clinical classification and ultrastructural findings in amelogenesis imperfecta

    International Nuclear Information System (INIS)

    Baeckman, B.; Lundgren, T.; Engstroem, E.U.; Falk, L.K.L.; Chabala, J.M.; Levi-Setti, R.; Noren, J.G.

    1993-01-01

    This study was performed to examine whether a clinical classification of different phenotypes of amelogenesis imperfecta could be discernible at the ultrastructural level. 17 primary teeth from 16 children with hypomineralization, hypomaturation, or hypoplastic variants of the disease were collected for histologic studies of the enamel by means of polarized light microscopy, scanning electron microscopy (SEM), and secondary ion mass spectrometry (SIMS). Polarization microscopy showed that the enamel was hypomineralized; in 6 teeth a wavy configuration of the enamel prisms also appeared. Three histomorphologic main types could be discerned. In 10 of the teeth extensive hypermineralization of the bulk of the enamel was found. 1 tooth had an unusually tick enamel with only a thin normally mineralized surface layer. SIMS images showed less pronounced signals from Ca 2+ and Na + , but with stronger signals from Cl - and CN - , representing the organic component of enamel. The SEM images showed an irregular prism pattern with marked interprismatic areas. Irrespective of the clinical appearance or the herediatary pattern the main findings were hypomineralized enamel with or without wavy bands. Neither of the analytical methods used in this paper distinguishes between the clinical phenotypes of amelogenesis imperfecta. 35 refs., 9 figs., 1 tab

  15. The absence of correlations between a clinical classification and ultrastructural findings in amelogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Baeckman, B.; Lundgren, T.; Engstroem, E.U.; Falk, L.K.L.; Chabala, J.M.; Levi-Setti, R.; Noren, J.G. (Dept. of Pedodontics, Univ. of Goeteborg (Sweden))

    1993-01-01

    This study was performed to examine whether a clinical classification of different phenotypes of amelogenesis imperfecta could be discernible at the ultrastructural level. 17 primary teeth from 16 children with hypomineralization, hypomaturation, or hypoplastic variants of the disease were collected for histologic studies of the enamel by means of polarized light microscopy, scanning electron microscopy (SEM), and secondary ion mass spectrometry (SIMS). Polarization microscopy showed that the enamel was hypomineralized; in 6 teeth a wavy configuration of the enamel prisms also appeared. Three histomorphologic main types could be discerned. In 10 of the teeth extensive hypermineralization of the bulk of the enamel was found. 1 tooth had an unusually tick enamel with only a thin normally mineralized surface layer. SIMS images showed less pronounced signals from Ca[sup 2+] and Na[sup +], but with stronger signals from Cl[sup -] and CN[sup -], representing the organic component of enamel. The SEM images showed an irregular prism pattern with marked interprismatic areas. Irrespective of the clinical appearance or the herediatary pattern the main findings were hypomineralized enamel with or without wavy bands. Neither of the analytical methods used in this paper distinguishes between the clinical phenotypes of amelogenesis imperfecta. 35 refs., 9 figs., 1 tab.

  16. Mineral features of connective dental hard tissues in hypoplastic amelogenesis imperfecta.

    Science.gov (United States)

    Kammoun, R; Behets, C; Mansour, L; Ghoul-Mazgar, S

    2018-04-01

    To explore the mineral features of dentin and cementum in hypoplastic Amelogenesis imperfecta AI teeth. Forty-four (44) teeth cleaned and free of caries were used: 20 control and 24 affected by hypoplastic amelogenesis imperfecta. Thirty-two teeth were studied by pQCT, cut in sections, and analyzed under microradiography, polarized light microscopy, and confocal Raman spectroscopy. Eight teeth were observed under scanning electron microscope. Four teeth were used for an X-ray diffraction. The mineral density data were analyzed statistically with the Mann-Whitney U test, using GraphPad InStat software. Both coronal dentin and radicular dentin were less mineralized in AI teeth when compared to control (respectively 6.2% and 6.8%; p < .001). Root dentinal walls were thin and irregular, while the cellular cementum layers were thick, reaching sometimes the cervical region of the tooth. Regular dentinal tubules and sclerotic dentin areas were noticed. Partially tubular or cellular dysplastic dentin and hyper-, normo-, or hypomineralized areas were noticed in the inter-radicular areas of hypoplastic AI teeth. The main mineral component was carbonate hydroxyapatite as explored by Raman spectroscopy and X-ray diffraction. Dentin and cementum in hypoplastic AI teeth are (i) hypomineralized, (ii) constituted of carbonate hydroxyapatite, and (iii) of non-homogenous structure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  17. 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

    OpenAIRE

    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 ...

  18. Enamelin (Enam) is essential for amelogenesis: ENU-induced mouse mutants as models for different clinical subtypes of human amelogenesis imperfecta (AI).

    Science.gov (United States)

    Masuya, Hiroshi; Shimizu, Kunihiko; Sezutsu, Hideki; Sakuraba, Yoshiyuki; Nagano, Junko; Shimizu, Aya; Fujimoto, Naomi; Kawai, Akiko; Miura, Ikuo; Kaneda, Hideki; Kobayashi, Kimio; Ishijima, Junko; Maeda, Takahide; Gondo, Yoichi; Noda, Tetsuo; Wakana, Shigeharu; Shiroishi, Toshihiko

    2005-03-01

    Amelogenesis imperfecta (AI) is a group of commonly inherited defects of dental enamel formation, which exhibits marked genetic and clinical heterogeneity. The genetic basis of this heterogeneity is still poorly understood. Enamelin, the affected gene product in one form of AI (AIH2), is an extracellular matrix protein that is one of the components of enamel. We isolated three ENU-induced dominant mouse mutations, M100395, M100514 and M100521, which caused AI-like phenotypes in the incisors and molars of the affected individuals. Linkage analyses mapped each of the three mutations to a region of chromosome 5 that contained the genes encoding enamelin (Enam) and ameloblastin (Ambn). Sequence analysis revealed that each mutation was a single-base substitution in Enam. M100395 (Enam(Rgsc395)) and M100514 (Enam(Rgsc514)) were putative missense mutations that caused S to I and E to G substitutions at positions 55 and 57 of the translated protein, respectively. Enam(Rgsc395) and Enam(Rgsc514) heterozygotes showed severe breakage of the enamel surface, a phenotype that resembled local hypoplastic AI. The M100521 mutation (Enam(Rgsc521)) was a T to A substitution at the splicing donor site in intron 4. This mutation resulted in a frameshift that gave rise to a premature stop codon. The transcript of the Enam(Rgsc521) mutant allele was degraded, indicating that Enam(Rgsc521) is a loss-of-function mutation. Enam(Rgsc521) heterozygotes showed a hypomaturation-type AI phenotype in the incisors, possibly due to haploinsufficiency of Enam. Enam(Rgsc521) homozygotes showed complete loss of enamel on the incisors and the molars. Thus, we report here that the Enam gene is essential for amelogenesis, and that mice with different point mutations at Enam may provide good animal models to study the different clinical subtypes of AI.

  19. Exclusion of known gene for enamel development in two Brazilian families with amelogenesis imperfecta.

    Science.gov (United States)

    Santos, Maria C L G; Hart, P Suzanne; Ramaswami, Mukundhan; Kanno, Cláudia M; Hart, Thomas C; Line, Sergio R P

    2007-01-31

    Amelogenesis imperfecta (AI) is a genetically heterogeneous group of diseases that result in defective development of tooth enamel. Mutations in several enamel proteins and proteinases have been associated with AI. The object of this study was to evaluate evidence of etiology for the six major candidate gene loci in two Brazilian families with AI. Genomic DNA was obtained from family members and all exons and exon-intron boundaries of the ENAM, AMBN, AMELX, MMP20, KLK4 and Amelotin gene were amplified and sequenced. Each family was also evaluated for linkage to chromosome regions known to contain genes important in enamel development. The present study indicates that the AI in these two families is not caused by any of the known loci for AI or any of the major candidate genes proposed in the literature. These findings indicate extensive genetic heterogeneity for non-syndromic AI.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta.

    Science.gov (United States)

    Wang, Xin; Zhao, Yuming; Yang, Yuan; Qin, Man

    2015-01-01

    Amelogenesis imperfecta is a group of inherited diseases affecting the quality and quantity of dental enamel. To date, mutations in more than ten genes have been associated with non-syndromic amelogenesis imperfecta (AI). Among these, ENAM and LAMB3 mutations are known to be parts of the etiology of hypoplastic AI in human cases. When both alleles of LAMB3 are defective, it could cause junctional epidermolysis bullosa (JEB), while with only one mutant allele in the C-terminus of LAMB3, it could result in severe hypoplastic AI without skin fragility. We enrolled three Chinese families with hypoplastic autosomal-dominant AI. Despite the diagnosis falling into the same type, the characteristics of their enamel hypoplasia were different. Screening of ENAM and LAMB3 genes was performed by direct sequencing of genomic DNA from blood samples. Disease-causing mutations were identified and perfectly segregated with the enamel defects in three families: a 19-bp insertion mutation in the exon 7 of ENAM (c.406_407insTCAAAAAAGCCGACCACAA, p.K136Ifs*16) in Family 1, a single-base deletion mutation in the exon 5 of ENAM (c. 139delA, p. M47Cfs*11) in Family 2, and a LAMB3 nonsense mutation in the last exon (c.3466C>T, p.Q1156X) in Family 3. Our results suggest that heterozygous mutations in ENAM and LAMB3 genes can cause hypoplastic AI with markedly different phenotypes in Chinese patients. And these findings extend the mutation spectrum of both genes and can be used for mutation screening of AI in the Chinese population.

  2. Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Amelogenesis imperfecta is a group of inherited diseases affecting the quality and quantity of dental enamel. To date, mutations in more than ten genes have been associated with non-syndromic amelogenesis imperfecta (AI. Among these, ENAM and LAMB3 mutations are known to be parts of the etiology of hypoplastic AI in human cases. When both alleles of LAMB3 are defective, it could cause junctional epidermolysis bullosa (JEB, while with only one mutant allele in the C-terminus of LAMB3, it could result in severe hypoplastic AI without skin fragility. We enrolled three Chinese families with hypoplastic autosomal-dominant AI. Despite the diagnosis falling into the same type, the characteristics of their enamel hypoplasia were different. Screening of ENAM and LAMB3 genes was performed by direct sequencing of genomic DNA from blood samples. Disease-causing mutations were identified and perfectly segregated with the enamel defects in three families: a 19-bp insertion mutation in the exon 7 of ENAM (c.406_407insTCAAAAAAGCCGACCACAA, p.K136Ifs*16 in Family 1, a single-base deletion mutation in the exon 5 of ENAM (c. 139delA, p. M47Cfs*11 in Family 2, and a LAMB3 nonsense mutation in the last exon (c.3466C>T, p.Q1156X in Family 3. Our results suggest that heterozygous mutations in ENAM and LAMB3 genes can cause hypoplastic AI with markedly different phenotypes in Chinese patients. And these findings extend the mutation spectrum of both genes and can be used for mutation screening of AI in the Chinese population.

  3. Treatment plan in amelogenesis imperfecta: A structured literature review on treatment protocols and dedicating the best possible options

    Directory of Open Access Journals (Sweden)

    Azari A.

    2008-12-01

    Full Text Available "nAmelogenesis imperfecta is an inherited disease that disturbs the formation of the enamel. It occurs as two main categories, hypomineralized and hypoplastic. Both deciduous and permanent teeth are affected, and the disorder may create unaesthetic appearance, dental sensitivity, and severe attrition. In this article through performing a structured literature review, numerous treatment modalities which so far advocated in rehabilitation of amelogenesis imperfecta in adults and children is discussed. The progressive changes on open bite, the problem of bonding during restorative phase of treatment , the rehabilitation difficulties of deciduous as well as permanent teeth is also discussed in detail and finally the interdisciplinary approach for treatment of this disability is demonstrated and some points for decision making in treatment protocols are suggested.

  4. Rehabilitation of a patient with amelogenesis imperfecta using porcelain veneers and CAD/CAM polymer restorations: A clinical report.

    Science.gov (United States)

    Saeidi Pour, Reza; Edelhoff, Daniel; Prandtner, Otto; Liebermann, Anja

    2015-01-01

    The complete dental rehabilitation of patients with a vertical dimension loss (VDL) caused by structural enamel deficits associated with amelogenesis imperfecta (AI) represents a difficult challenge for restorative teams. Accurate analysis and treatment planning that includes esthetic and functional evaluations and adequate material selection are important prerequisites for successful results. Long-term provisional restorations play an important role in exploring and elucidating the patients' esthetic demands and functional needs. Restorative treatment options can vary from requiring only oral hygiene instructions to extensive dental restorations that include composite fillings, ceramic veneers, metal-ceramic, or all-ceramic crowns. This case report describes a full-mouth rehabilitation of a patient with amelogenesis imperfecta including the case planning, bite replacement, preparation, and restoration setting steps with an experimental CAD/CAM polymer and porcelain veneers.

  5. Amelogenesis Imperfecta: A Non-Invasive Approach to Improve Esthetics in Young Patients. Report of Two Cases.

    Science.gov (United States)

    Cagetti, Maria Grazia; Cattaneo, Stefano; Hu, Ye Qing; Campus, Guglielmo

    Objective-Evaluate esthetic and functional efficacy of infiltrant resin (Icon, DMG, Hamburg, Germany) in Amelogenesis Imperfecta's treatment. Two adolescent patients, G.S. (13 years old) and C.M. (15 years old), affected by the hypomaturation type of Amelogenesis Imperfecta, were treated with Icon resin and were followed for twelve months. Treated teeth show an excellent aesthetical result immediately after the resin application, effect that lasts in the long-term (six and twelve months follow-up examinations); the dental wear's progression seems to be clinically arrested. Resin infiltration has proven to be a minimal invasive treatment for dental discoloration, less aggressive than conventional procedures. This approach might be recommended for a stable esthetical improvement in moderate AI's lesions especially in children and adolescents.

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

    Science.gov (United States)

    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.

  7. Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis Imperfecta.

    Science.gov (United States)

    Parry, David A; Smith, Claire E L; El-Sayed, Walid; Poulter, James A; Shore, Roger C; Logan, Clare V; Mogi, Chihiro; Sato, Koichi; Okajima, Fumikazu; Harada, Akihiro; Zhang, Hong; Koruyucu, Mine; Seymen, Figen; Hu, Jan C-C; Simmer, James P; Ahmed, Mushtaq; Jafri, Hussain; Johnson, Colin A; Inglehearn, Chris F; Mighell, Alan J

    2016-10-06

    Amelogenesis is the process of dental enamel formation, leading to the deposition of the hardest tissue in the human body. This process requires the intricate regulation of ion transport and controlled changes to the pH of the developing enamel matrix. The means by which the enamel organ regulates pH during amelogenesis is largely unknown. We identified rare homozygous variants in GPR68 in three families with amelogenesis imperfecta, a genetically and phenotypically heterogeneous group of inherited conditions associated with abnormal enamel formation. Each of these homozygous variants (a large in-frame deletion, a frameshift deletion, and a missense variant) were predicted to result in loss of function. GPR68 encodes a proton-sensing G-protein-coupled receptor with sensitivity in the pH range that occurs in the developing enamel matrix during amelogenesis. Immunohistochemistry of rat mandibles confirmed localization of GPR68 in the enamel organ at all stages of amelogenesis. Our data identify a role for GPR68 as a proton sensor that is required for proper enamel formation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused by CLDN19 gene mutations.

    Science.gov (United States)

    Yamaguti, Paulo Marcio; Neves, Francisco de Assis Rocha; Hotton, Dominique; Bardet, Claire; de La Dure-Molla, Muriel; Castro, Luiz Claudio; Scher, Maria do Carmo; Barbosa, Maristela Estevão; Ditsch, Christophe; Fricain, Jean-Christophe; de La Faille, Renaud; Figueres, Marie-Lucile; Vargas-Poussou, Rosa; Houillier, Pascal; Chaussain, Catherine; Babajko, Sylvie; Berdal, Ariane; Acevedo, Ana Carolina

    2017-01-01

    Amelogenesis imperfecta (AI) is a group of genetic diseases characterised by tooth enamel defects. AI was recently described in patients with familial hypercalciuria and hypomagnesaemia with nephrocalcinosis (FHHNC) caused by CLDN16 mutations. In the kidney, claudin-16 interacts with claudin-19 to control the paracellular passage of calcium and magnesium. FHHNC can be linked to mutations in both genes. Claudin-16 was shown to be expressed during amelogenesis; however, no data are available on claudin-19. Moreover, the enamel phenotype of patients with CLDN19 mutations has never been described. In this study, we describe the clinical and genetic features of nine patients with FHHNC carrying CLDN19 mutations and the claudin-19 expression profile in rat ameloblasts. Six FHHNC Brazilian patients were subjected to mutational analysis. Three additional French patients were recruited for orodental characterisation. The expression profile of claudin-19 was evaluated by RT-qPCR and immunofluorescence using enamel epithelium from rat incisors. All patients presented AI at different degrees of severity. Two new likely pathogenic variations in CLDN19 were found: p.Arg200Gln and p.Leu90Arg. RT-qPCR revealed low Cldn19 expression in ameloblasts. Confocal analysis indicated that claudin-19 was immunolocalised at the distal poles of secretory and maturing ameloblasts. For the first time, it was demonstrated that AI is associated with FHHNC in patients carrying CLDN19 mutations. The data suggest claudin-19 as an additional determinant in enamel formation. Indeed, the coexistence of hypoplastic and hypomineralised AI in the patients was consistent with claudin-19 expression in both secretory and maturation stages. Additional indirect systemic effects cannot be excluded. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    2012-01-01

    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 autosomal recessive AI patients

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

    Science.gov (United States)

    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 (P<.05). Representative fractured beams from each group were examined under scanning electron microscopy. Both factors, dentine substrate (P<.001) and etching step (P<.05), and their interactions (P<.001), were statistically significant. Additional etching had an adverse effect on the bond strength of Clearfil SE Bond to normal dentine (P<.005), and no significant improvement was found for AI-affected dentine (P=.479). Additional acid etching does not improve the bond strength of a self-etch adhesive to AI-affected dentine. © 2017 John Wiley & Sons Australia, Ltd.

  13. Management of Amelogenesis Imperfecta: A 15-Year Case History of Two Siblings.

    Science.gov (United States)

    Dursun, E; Savard, E; Vargas, C; Loison-Robert, L; Cherifi, H; Bdeoui, F; Landru, M-M

    Amelogenesis imperfecta (AI) is a heterogenous genetic disorder that interferes with normal enamel formation in the absence of systemic disorders. The patients' main concerns are caries susceptibility, poor esthetics, and generalized sensitivity. There is a broad clinical spectrum, from discolorations to consequent enamel alterations. This case report describes the 15-year case study and the full-mouth rehabilitation of two siblings affected by a hypocalcified AI. Clinical Considerations: In these two patients, conservative care with stainless steel crowns and direct composite restorations was undertaken to restore function and esthetics and to reduce sensitivities in primary and mixed dentitions. The difficulties in monitoring resulted in severe infectious complications (dental abscess with cutaneous fistula), important dental defects, and loss of spaces with subsequent malocclusion. In the young adult dentition, they were treated by extractions, root canal therapies, and new restorations: stainless steel crowns for permanent molars, direct composite restorations (with strip crowns) for incisors and maxillary canines (to improve the crown morphology as well as to mask the discolorations and the malpositions), and adjusted composite crown molds using a thermoforming procedure for premolars and the mandibular canines. The main difficulties were rapid tooth surface loss, bonding to atypical enamel, developing dentition, long-term follow-up. Restoring function and esthetics in AI-affected patients is a challenge from primary to adult dentition. Early corrections are essential to avoid dental damage and for psychological benefits. This clinical report highlights the adhesive rehabilitation for anterior and premolar areas and the difficulty of patient follow-up.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Unexpected identification of a recurrent mutation in the DLX3 gene causing amelogenesis imperfecta.

    Science.gov (United States)

    Kim, Y-J; Seymen, F; Koruyucu, M; Kasimoglu, Y; Gencay, K; Shin, T J; Hyun, H-K; Lee, Z H; Kim, J-W

    2016-05-01

    To identify the molecular genetic aetiology of a family with autosomal dominant amelogenesis imperfecta (AI). DNA samples were collected from a six-generation family, and the candidate gene approach was used to screen for the enamelin (ENAM) gene. Whole-exome sequencing and linkage analysis with SNP array data identified linked regions, and candidate gene screening was performed. Mutational analysis revealed a mutation (c.561_562delCT and p.Tyr188Glnfs*13) in the DLX3 gene. After finding a recurrent DLX3 mutation, the clinical phenotype of the family members was re-examined. The proband's mother had pulp elongation in the third molars. The proband had not hair phenotype, but her cousin had curly hair at birth. In this study, we identified a recurrent 2-bp deletional DLX3 mutation in a new family. The clinical phenotype was the mildest one associated with the DLX3 mutations. These results will advance the understanding of the functional role of DLX3 in developmental processes. © 2016 The Authors. Oral Diseases Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Marquezin, Maria Carolina Salomé; Zancopé, Bruna Raquel; Pacheco, Larissa Ferreira; Gavião, Maria Beatriz Duarte; Pascon, Fernanda Miori

    2015-01-01

    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. PMID:25705526

  17. Deletion of amelotin exons 3-6 is associated with amelogenesis imperfecta.

    Science.gov (United States)

    Smith, Claire E L; Murillo, Gina; Brookes, Steven J; Poulter, James A; Silva, Sandra; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2016-08-15

    Amelogenesis imperfecta (AI) is a heterogeneous group of genetic conditions that result in defective dental enamel formation. Amelotin (AMTN) is a secreted protein thought to act as a promoter of matrix mineralization in the final stage of enamel development, and is strongly expressed, almost exclusively, in maturation stage ameloblasts. Amtn overexpression and Amtn knockout mouse models have defective enamel with no other associated phenotypes, highlighting AMTN as an excellent candidate gene for human AI. However, no AMTN mutations have yet been associated with human AI. Using whole exome sequencing, we identified an 8,678 bp heterozygous genomic deletion encompassing exons 3-6 of AMTN in a Costa Rican family segregating dominant hypomineralised AI. The deletion corresponds to an in-frame deletion of 92 amino acids, shortening the protein from 209 to 117 residues. Exfoliated primary teeth from an affected family member had enamel that was of a lower mineral density compared to control enamel and exhibited structural defects at least some of which appeared to be associated with organic material as evidenced using elemental analysis. This study demonstrates for the first time that AMTN mutations cause non-syndromic human AI and explores the human phenotype, comparing it with that of mice with disrupted Amtn function. © The Author 2016. Published by Oxford University Press.

  18. Nephrocalcinosis in Amelogenesis Imperfecta Caused by the FAM20A Mutation.

    Science.gov (United States)

    Koruyucu, Mine; Seymen, Figen; Gencay, Genco; Gencay, Koray; Tuna, Elif Bahar; Shin, Teo Jeon; Hyun, Hong-Keun; Kim, Young-Jae; Kim, Jung-Wook

    2018-01-01

    Enamel-renal syndrome is characterized by nephrocalcinosis, enamel defects, gingival hyperplasia and eruption failures. It has been recently identified that recessive mutations in the FAM20A gene result in amelogenesis imperfecta (AI)-gingival fibromatosis. The aim of this research to determine whether AI patients with known -FAM20A mutations also have nephrocalcinosis. Complete oral and radiological examinations were performed for all participating family members. Renal examinations were performed using ultrasound. The teeth were evaluated for severe loss, and multiple eruption failures were evident from the clinical and radiological examinations. Unexpected extensive and fast crown resorption was found by radiological examination. Renal ultrasound revealed bilateral nephrocalcinosis in both affected individuals. Recessive FAM20A mutations can cause nephrocalcinosis in addition to the oral phenotype. AI patients with similar clinical phenotypes and FAM20A mutations should be examined for nephropathy even if they lack pertinent symptoms. Nephrology referral is warranted for patients who have clinical phenotypes related to AI-gingival fibromatosis even if they are not symptomatic. © 2018 S. Karger AG, Basel.

  19. 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...

  20. Cone-rod dystrophy and amelogenesis imperfecta (Jalili syndrome): phenotypes and environs.

    Science.gov (United States)

    Jalili, I K

    2010-11-01

    To report a new phenotype with additional data on the oculo-dental syndrome of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) caused by mutations on CNNM4, a metal transporter, with linkage at achromatopsia locus 2q11 (Jalili syndrome). Three siblings aged 5, 6, and 10 years from a six-generation Arab family in Gaza City underwent full systemic, ophthalmic, and dental examinations, investigations and detailed genealogy. Subjects presented at early childhood with visual impairment and abnormal dentition together with photophobia and fine nystagmus increasing under photopic conditions, in the presence of normal fundi. Electrophysiologically, photopic flicker responses were impaired; scotopic responses were extinguished at the age of 10 years. Anterior open bite accompanied AI in all siblings. The syndrome formed 83% of CRD cases in the Gaza Strip, which has a prevalence of 1 : 10,000. On the basis of clinical features and electrophysiology, two phenotypes exist: an infancy onset form with progressive macular lesion and an early childhood onset form with normal fundi. More prevalent than previously thought, Jalili syndrome presents a model of the effect of different mutations of the same genetic defect, observations of the same phenotype at different stages of the natural history of the disease, and the influence of epigenetic and tissue-specific factors as causes of phenotypic variability. The paper calls for action to tackle consanguinity in endogamous communities, addresses the possible role of high fluoride levels in groundwater as a trigger for genetic mutations, and the use of red-tinted filter in cone disorders.

  1. Amelogenesis imperfecta in two families with defined AMELX deletions in ARHGAP6.

    Directory of Open Access Journals (Sweden)

    Jan C-C Hu

    Full Text Available Amelogenesis imperfecta (AI is a group of inherited conditions featuring isolated enamel malformations. About 5% of AI cases show an X-linked pattern of inheritance, which are caused by mutations in AMELX. In humans there are two, non-allelic amelogenin genes: AMELX (Xp22.3 and AMELY (Yp11.2. About 90% of amelogenin expression is from AMELX, which is nested within intron 1 of the gene encoding Rho GTPase activating protein 6 (ARHGAP6. We recruited two AI families and determined that their disease-causing mutations were partial deletions in ARHGAP6 that completely deleted AMELX. Affected males in both families had a distinctive enamel phenotype resembling "snow-capped" teeth. The 96,240 bp deletion in family 1 was confined to intron 1 of ARHGAP6 (g.302534_398773del96240, but removed alternative ARHGAP6 promoters 1c and 1d. Analyses of developing teeth in mice showed that ARHGAP6 is not expressed from these promoters in ameloblasts. The 52,654 bp deletion in family 2 (g.363924_416577del52654insA removed ARHGAP6 promoter 1d and exon 2, precluding normal expression of ARHGAP6. The male proband of family 2 had slightly thinner enamel with greater surface roughness, but exhibited the same pattern of enamel malformations characteristic of males in family 1, which themselves showed minor variations in their enamel phenotypes. We conclude that the enamel defects in both families were caused by amelogenin insufficiency, that deletion of AMELX results in males with a characteristic snow-capped enamel phenotype, and failed ARHGAP6 expression did not appreciably alter the severity of enamel defects when AMELX was absent.

  2. Temporary restorative treatment in children and adolescents with amelogenesis imperfecta: Scoping review.

    Directory of Open Access Journals (Sweden)

    Cristhian Cisneros

    2017-12-01

    Full Text Available Background: Amelogenesis imperfecta (AI is a group of disorders that affect the enamel of the teeth, either in quality or quantity. This alteration causes sensitivity and is associated with factors that could affect the strength of the adhesive bond of the restorative material. Aim: To review the literature regarding the most used temporary restorative treatment in children and adolescents with AI. Methods: This scoping review aimed to include case reports, literature reviews and original studies that evaluated restorative materials for the teeth of children and adolescents with AI. Editorials, meeting abstracts and letters to the editor were excluded. The following electronic databases were used: Medline (Ovid, PubMed, Ebsco, Scopus (Elsevier and Web of Science (Thomson Reuters. Manual searches in the reference lists of the included articles were also carried out. Finally, a search in Google Scholar restricted to the first 100 hits was performed. Duplicates were eliminated upon identification. The search covered a period between the years of 2011 and 2016. PRISMA guidelines were used for reporting the review. The evidence ranking was carried out by means of the Oxford criteria. Results: Six articles met the eligibility criteria and were included in this scoping review. Three articles were case reports, one was a review and two were original studies. For the treatment of AI, direct or indirect composite resins were the most commonly used material of choice in the retrieved studies because they demonstrate greater longevity, aesthetics and function compared to the other materials used. Conclusions: Among children and adolescents with AI, the temporary restorative treatment that demonstrated better long-term results in permanent teeth was the direct and indirect composite resins. However, high quality studies should be conducted to confirm the results presented herein.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Amelogenesis imperfecta caused by N-terminal enamelin point mutations in mice and men is driven by endoplasmic reticulum stress.

    Science.gov (United States)

    Brookes, Steven J; Barron, Martin J; Smith, Claire E L; Poulter, James A; Mighell, Alan J; Inglehearn, Chris F; Brown, Catriona J; Rodd, Helen; Kirkham, Jennifer; Dixon, Michael J

    2017-05-15

    'Amelogenesis imperfecta' (AI) describes a group of inherited diseases of dental enamel that have major clinical impact. Here, we identify the aetiology driving AI in mice carrying a p.S55I mutation in enamelin; one of the most commonly mutated proteins underlying AI in humans. Our data indicate that the mutation inhibits the ameloblast secretory pathway leading to ER stress and an activated unfolded protein response (UPR). Initially, with the support of the UPR acting in pro-survival mode, Enamp.S55I heterozygous mice secreted structurally normal enamel. However, enamel secreted thereafter was structurally abnormal; presumably due to the UPR modulating ameloblast behaviour and function in an attempt to relieve ER stress. Homozygous mutant mice failed to produce enamel. We also identified a novel heterozygous ENAMp.L31R mutation causing AI in humans. We hypothesize that ER stress is the aetiological factor in this case of human AI as it shared the characteristic phenotype described above for the Enamp.S55I mouse. We previously demonstrated that AI in mice carrying the Amelxp.Y64H mutation is a proteinopathy. The current data indicate that AI in Enamp.S55I mice is also a proteinopathy, and based on comparative phenotypic analysis, we suggest that human AI resulting from the ENAMp.L31R mutation is another proteinopathic disease. Identifying a common aetiology for AI resulting from mutations in two different genes opens the way for developing pharmaceutical interventions designed to relieve ER stress or modulate the UPR during enamel development to ameliorate the clinical phenotype. © The Author 2017. Published by Oxford University Press.

  6. 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

  7. Identification of a novel FAM83H mutation and microhardness of an affected molar in autosomal dominant hypocalcified amelogenesis imperfecta.

    Science.gov (United States)

    Hyun, H-K; Lee, S-K; Lee, K-E; Kang, H-Y; Kim, E-J; Choung, P-H; Kim, J-W

    2009-11-01

    To determine the underlying molecular genetic aetiology of a family with the hypocalcified form of amelogenesis imperfecta and to investigate the hardness of the enamel and dentine of a known FAM83H mutation. Mutational screening of the FAM83H on the basis of candidate gene approach was performed. All exons and exon-intron boundaries was amplified and sequenced. A microhardness test was performed to measure the Vickers microhardness value. A novel nonsense mutation (c.1354C>T, p.Q452X) was identified in the last exon of FAM83H, which resulted in soft, uncalcified enamel. The affected enamel was extremely soft (about 17% of the normal control), but the underlying dentine was as hard as the normal control. Mutational analysis revealed a novel mutation in FAM83H gene. Hardness of dentine was not affected by the mutation, whilst the enamel was extremely soft.

  8. 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.

  9. Whole-exome sequencing, without prior linkage, identifies a mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta.

    Science.gov (United States)

    Poulter, James A; El-Sayed, Walid; Shore, Roger C; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2014-01-01

    The conventional approach to identifying the defective gene in a family with an inherited disease is to find the disease locus through family studies. However, the rapid development and decreasing cost of next generation sequencing facilitates a more direct approach. Here, we report the identification of a frameshift mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta (AI). Whole-exome sequencing of three affected family members and subsequent filtering of shared variants, without prior genetic linkage, sufficed to identify the pathogenic variant. Simultaneous analysis of multiple family members confirms segregation, enhancing the power to filter the genetic variation found and leading to rapid identification of the pathogenic variant. LAMB3 encodes a subunit of Laminin-5, one of a family of basement membrane proteins with essential functions in cell growth, movement and adhesion. Homozygous LAMB3 mutations cause junctional epidermolysis bullosa (JEB) and enamel defects are seen in JEB cases. However, to our knowledge, this is the first report of dominant AI due to a LAMB3 mutation in the absence of JEB.

  10. Identification of the first multi-exonic WDR72 deletion in isolated amelogenesis imperfecta, and generation of a WDR72-specific copy number screening tool.

    Science.gov (United States)

    Hentschel, Julia; Tatun, Dana; Parkhomchuk, Dmitri; Kurth, Ingo; Schimmel, Bettina; Heinrich-Weltzien, Roswitha; Bertzbach, Sabine; Peters, Hartmut; Beetz, Christian

    2016-09-15

    Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous disorder of tooth development which is due to aberrant deposition or composition of enamel. Both syndromic and isolated forms exist; they may be inherited in an X-linked, autosomal recessive, or autosomal dominant manner. WDR72 is one of ten currently known genes for recessive isolated AI; nine WDR72 mutations affecting single nucleotides have been described to date. Based on whole exome sequencing in a large consanguineous AI pedigree, we obtained evidence for presence of a multi-exonic WDR72 deletion. A home-made multiplex ligation-dependent probe amplification assay was used to confirm the aberration, to narrow its extent, and to identify heterozygous carriers. Our study extends the mutational spectrum for WDR72 to include large deletions, and supports a relevance of the previously proposed loss-of-function mechanism. It also introduces an easy-to-use and highly sensitive tool for detecting WDR72 copy number alterations. Copyright © 2016. Published by Elsevier B.V.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Noninvasive and multidisciplinary approach to the functional and esthetic rehabilitation of amelogenesis imperfecta: a pediatric case report.

    Science.gov (United States)

    de Souza, Juliana Feltrin; Fragelli, Camila Maria Bullio; Paschoal, Marco Aurélio Benini; Campos, Edson Alves; Cunha, Leonardo Fernandes; Losso, Estela Maris; Cordeiro, Rita de Cássia Loiola

    2014-01-01

    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.

  13. Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta.

    Science.gov (United States)

    Parry, David A; Brookes, Steven J; Logan, Clare V; Poulter, James A; El-Sayed, Walid; Al-Bahlani, Suhaila; Al Harasi, Sharifa; Sayed, Jihad; Raïf, El Mostafa; Shore, Roger C; Dashash, Mayssoon; Barron, Martin; Morgan, Joanne E; Carr, Ian M; Taylor, Graham R; Johnson, Colin A; Aldred, Michael J; Dixon, Michael J; Wright, J Tim; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2012-09-07

    Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein's phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  14. Mutations in C4orf26, Encoding a Peptide with In Vitro Hydroxyapatite Crystal Nucleation and Growth Activity, Cause Amelogenesis Imperfecta

    Science.gov (United States)

    Parry, David A.; Brookes, Steven J.; Logan, Clare V.; Poulter, James A.; El-Sayed, Walid; Al-Bahlani, Suhaila; Al Harasi, Sharifa; Sayed, Jihad; Raïf, El Mostafa; Shore, Roger C.; Dashash, Mayssoon; Barron, Martin; Morgan, Joanne E.; Carr, Ian M.; Taylor, Graham R.; Johnson, Colin A.; Aldred, Michael J.; Dixon, Michael J.; Wright, J. Tim; Kirkham, Jennifer; Inglehearn, Chris F.; Mighell, Alan J.

    2012-01-01

    Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein’s phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis. PMID:22901946

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. 15-year follow-up of a case of amelogenesis imperfecta: importance of psychological aspect and impact on quality of life.

    Science.gov (United States)

    Trentesaux, T; Rousset, M M; Dehaynin, E; Laumaillé, M; Delfosse, C

    2013-02-01

    Amelogenesis imperfecta (AI) represents a group of hereditary conditions which affects enamel formation in the primary and permanent dentitions. Gene mutations alter the quality and/or quantity of enamel. AI often has severe consequences for the patient such as high tooth sensitivity, low aesthetic quality of the dentition, and poor mechanical properties of the dental tissues. This can result in reduced oral health-related quality of life. We present the case of a child affected by AI which had been diagnosed at the age of 9 years. Teeth presented many enamel defects. The patient presented thin brown to yellow enamel and the surface was rough and granular. He revealed short clinical crowns, occlusal wear with exposed dentine in posterior areas. He also presented a lateral open bite and lingual lateral interposition due to partial destruction of deciduous molars. Panoramic radiograph showed no differences between enamel and dentine appearance and also coronary destruction of permanent molars. The initial treatment consisted of adaptation of composite resins on permanent incisors to improve aesthetics. Preformed metal crowns were placed on first permanent molars to prevent their premature destruction. This was disrupted for a variety of reasons. Fourteen years later, after a dental nomadism, the patient consulted by chance a dentist who identified his genetic pathology and was aware of its consequences. Extensive prosthodontic treatment was needed, but oral hygiene was poor and gingivitis remained. Dealing with high loss of motivation has been one of the main challenges because this patient had a lot of psychological problems. He was concerned, as are many patients affected by AI or other enamel abnormalities. This paper highlights the difficulties of long-term care of this dental abnormality. Psychological aspects of the quality of life, which is a common feature in patients suffering from many kinds of enamel anomalies, are very important.

  17. 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.

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

    Science.gov (United States)

    Gasse, Barbara; Prasad, Megana; Delgado, Sidney; Huckert, Mathilde; Kawczynski, Marzena; Garret-Bernardin, Annelyse; Lopez-Cazaux, Serena; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Stoetzel, Corinne; Bloch-Zupan, Agnès; Sire, Jean-Yves

    2017-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Haubek, Dorte; Gjørup, Hans; Jensen, Lillian G; Juncker, Inger; Nyegaard, Mette; Børglum, Anders D; Poulsen, Sven; Hertz, Jens M

    2011-11-01

    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 the gingival margin seemed resistant to posteruptive loss of enamel. We have screened FAM83H in another five unrelated Danish patients with a phenotype of ADHCAI similar to that in the five-generation family, and identified a de novo FAM83H nonsense mutation, p.Q452X in one of these patients. CONCLUSION.  We have identified a FAM83H mutation in two of six unrelated families with ADHCAI and found limited phenotypic variation of the enamel in these patients. © 2011 The Authors. International Journal of Paediatric Dentistry © 2011 BSPD, IAPD and Blackwell Publishing Ltd.

  1. 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

  2. The genetics of amelogenesis imperfecta: a review of the literature Genética da amelogênese imperfeita: uma revisão da literatura

    Directory of Open Access Journals (Sweden)

    Maria Cristina Leme Godoy dos Santos

    2005-09-01

    Full Text Available A melogenesis imperfecta (AI is a group of inherited defects of dental enamel formation that show both clinical and genetic heterogeneity. Enamel findings in AI are highly variable, ranging from deficient enamel formation to defects in the mineral and protein content. Enamel formation requires the expression of multiple genes that transcribes matrix proteins and proteinases needed to control the complex process of crystal growth and mineralization. The AI phenotypes depend on the specific gene involved, the location and type of mutation, and the corresponding putative change at the protein level. Different inheritance patterns such as X-linked, autosomal dominant and autosomal recessive types have been reported. Mutations in the amelogenin, enamelin, and kallikrein-4 genes have been demonstrated to result in different types of AI and a number of other genes critical to enamel formation have been identified and proposed as candidates for AI. The aim of this article was to present an evaluation of the literature regarding role of proteins and proteinases important to enamel formation and mutation associated with AI.A melogênese imperfeita é um grupo de doenças hereditárias que causa defeito na formação esmalte dental e mostra heterogeneidade clínica e genética. O esmalte é afetado com alta variabilidade, desde deficiência na formação do esmalte até defeitos no conteúdo mineral e protéico. A formação do esmalte requer a expressão de múltiplos genes que transcrevem proteínas e proteinases importantes para controlar o complexo processo de crescimento dos cristais e mineralização. O fenótipo da AI depende do gene envolvido, sua localização e tipo de mutação, e a conseqüente alteração na proteína. Diferentes padrões hereditários com ligado ao X, autossômico dominante e autossômico recessivo já foram descritos. Mutações nos genes correspondentes da amelogenina, enamelina, e calicreína-4 demonstraram resultar em

  3. Osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    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.

  4. MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways-Novel Insight into the Origins of Enamel Pathologies.

    Science.gov (United States)

    Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L; Hacia, Joseph G; Paine, Michael L

    2017-03-13

    Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3'-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Regulation of pH During Amelogenesis.

    Science.gov (United States)

    Lacruz, Rodrigo S; Nanci, Antonio; Kurtz, Ira; Wright, J Timothy; Paine, Michael L

    2010-02-01

    During amelogenesis, extracellular matrix proteins interact with growing hydroxyapatite crystals to create one of the most architecturally complex biological tissues. The process of enamel formation is a unique biomineralizing system characterized first by an increase in crystallite length during the secretory phase of amelogenesis, followed by a vast increase in crystallite width and thickness in the later maturation phase when organic complexes are enzymatically removed. Crystal growth is modulated by changes in the pH of the enamel microenvironment that is critical for proper enamel biomineralization. Whereas the genetic bases for most abnormal enamel phenotypes (amelogenesis imperfecta) are generally associated with mutations to enamel matrix specific genes, mutations to genes involved in pH regulation may result in severely affected enamel structure, highlighting the importance of pH regulation for normal enamel development. This review summarizes the intra- and extracellular mechanisms employed by the enamel-forming cells, ameloblasts, to maintain pH homeostasis and, also, discusses the enamel phenotypes associated with disruptions to genes involved in pH regulation.

  9. 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

  10. MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways–Novel Insight into the Origins of Enamel Pathologies

    Science.gov (United States)

    Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L.; Hacia, Joseph G.; Paine, Michael L.

    2017-01-01

    Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3′-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI. PMID:28287144

  11. Carriers with functional null mutations in LAMA3 have localized enamel abnormalities due to haploinsufficiency

    NARCIS (Netherlands)

    Gostynska, Katarzyna B.; Yuen, Wing Yan; Pasmooij, Anna Maria Gerdina; Stellingsma, Cornelius; Pas, Hendri H.; Lemmink, Henny; Jonkman, Marcel F.

    2017-01-01

    The hereditary blistering disease junctional epidermolysis bullosa (JEB) is always accompanied by structural enamel abnormalities of primary and secondary dentition, characterized as amelogenesis imperfecta. Autosomal recessive mutations in LAMA3, LAMB3 and LAMC2 encoding the heterotrimer laminin

  12. What Is Osteogenesis Imperfecta?

    Science.gov (United States)

    ... Series of Publications for the Public What Is Osteogenesis Imperfecta? Fast Facts: An Easy-to-Read Series of ... on Osteogenesis Imperfecta? For More Information What Causes Osteogenesis Imperfecta? OI is caused by one of several genes ...

  13. Deciphering defective amelogenesis using in vitro culture systems.

    Science.gov (United States)

    Arinawati, Dian Yosi; Miyoshi, Keiko; Tanimura, Ayako; Horiguchi, Taigo; Hagita, Hiroko; Noma, Takafumi

    2018-04-01

    The conventional two-dimensional (2D) in vitro culture system is frequently used to analyze the gene expression with or without extracellular signals. However, the cells derived from primary culture and cell lines frequently deviate the gene expression profile compared to the corresponding in vivo samples, which sometimes misleads the actual gene regulation in vivo. To overcome this gap, we developed the comparative 2D and 3D in vitro culture systems and applied them to the genetic study of amelogenesis imperfecta (AI) as a model. Recently, we found specificity protein 6 (Sp6) mutation in an autosomal-recessive AI rat that was previously named AMI. We constructed 3D structure of ARE-B30 cells (AMI-derived rat dental epithelial cells) or G5 (control wild type cells) combined with RPC-C2A cells (rat pulp cell line) separated by the collagen membrane, while in 2D structure, ARE-B30 or G5 was cultured with or without the collagen membrane. Comparative analysis of amelogenesis-related gene expression in ARE-B30 and G5 using our 2D and 3D in vitro systems revealed distinct expression profiles, showing the causative outcomes. Bone morphogenetic protein 2 and follistatin were reciprocally expressed in G5, but not in ARE-B30 cells. All-or-none expression of amelotin, kallikrein-related peptidase 4, and nerve growth factor receptor was observed in both cell types. In conclusion, our in vitro culture systems detected the phenotypical differences in the expression of the stage-specific amelogenesis-related genes. Parallel analysis with 2D and 3D culture systems may provide a platform to understand the molecular basis for defective amelogenesis caused by Sp6 mutation. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. 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

  15. Circadian rhythms regulate amelogenesis.

    Science.gov (United States)

    Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

    2013-07-01

    Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of the development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24 h) intervals both at RNA and protein levels. This study also reveals that the two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory stage ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation stage ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stages of amelogenesis might be under circadian control. Changes in clock gene expression patterns might result in significant alterations of enamel apposition and mineralization. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. 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, ...

  17. 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

  18. Transcriptional factor DLX3 promotes the gene expression of enamel matrix proteins during amelogenesis.

    Science.gov (United States)

    Zhang, Zhichun; Tian, Hua; Lv, Ping; Wang, Weiping; Jia, Zhuqing; Wang, Sainan; Zhou, Chunyan; Gao, Xuejun

    2015-01-01

    Mutation of distal-less homeobox 3 (DLX3) is responsible for human tricho-dento-osseous syndrome (TDO) with amelogenesis imperfecta, indicating a crucial role of DLX3 in amelogenesis. However, the expression pattern of DLX3 and its specific function in amelogenesis remain largely unknown. The aim of this study was to investigate the effects of DLX3 on enamel matrix protein (EMP) genes. By immunohistochemistry assays of mouse tooth germs, stronger immunostaining of DLX3 protein was identified in ameloblasts in the secretory stage than in the pre-secretory and maturation stages, and the same pattern was found for Dlx3 mRNA using Realtime PCR. In a mouse ameloblast cell lineage, forced expression of DLX3 up-regulated the expression of the EMP genes Amelx, Enam, Klk4, and Odam, whereas knockdown of DLX3 down-regulated these four EMP genes. Further, bioinformatics, chromatin immunoprecipitation, and luciferase assays revealed that DLX3 transactivated Enam, Amelx, and Odam through direct binding to their enhancer regions. Particularly, over-expression of mutant-DLX3 (c.571_574delGGGG, responsible for TDO) inhibited the activation function of DLX3 on expression levels and promoter activities of the Enam, Amelx, and Odam genes. Together, our data show that DLX3 promotes the expression of the EMP genes Amelx, Enam, Klk4, and Odam in amelogenesis, while mutant-DLX3 disrupts this regulatory function, thus providing insights into the molecular mechanisms underlying the enamel defects of TDO disease.

  19. Dentinogenesis imperfecta in adults with osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Gjørup, Hans; Hald, Jannie Dahl; Schmidt, Malene

    Aims: To describe the prevalence and the clinical variation of dentinogenesis imperfecta (DI) in adults with various types of osteogenesis imperfecta (OI). Methods: A total of 72 patients with a medically confirmed diagnosis of OI were recruited from Aarhus University Hospital, Department...

  20. The Unfolded Protein Response in Amelogenesis and Enamel Pathologies

    Directory of Open Access Journals (Sweden)

    Steven J. Brookes

    2017-09-01

    Full Text Available During the secretory phase of their life-cycle, ameloblasts are highly specialized secretory cells whose role is to elaborate an extracellular matrix that ultimately confers both form and function to dental enamel, the most highly mineralized of all mammalian tissues. In common with many other “professional” secretory cells, ameloblasts employ the unfolded protein response (UPR to help them cope with the large secretory cargo of extracellular matrix proteins transiting their ER (endoplasmic reticulum/Golgi complex and so minimize ER stress. However, the UPR is a double-edged sword, and, in cases where ER stress is severe and prolonged, the UPR switches from pro-survival to pro-apoptotic mode. The purpose of this review is to consider the role of the ameloblast UPR in the biology and pathology of amelogenesis; specifically in respect of amelogenesis imperfecta (AI and fluorosis. Some forms of AI appear to correspond to classic proteopathies, where pathological intra-cellular accumulations of protein tip the UPR toward apoptosis. Fluorosis also involves the UPR and, while not of itself a classic proteopathic disease, shares some common elements through the involvement of the UPR. The possibility of therapeutic intervention by pharmacological modulation of the UPR in AI and fluorosis is also discussed.

  1. The Unfolded Protein Response in Amelogenesis and Enamel Pathologies.

    Science.gov (United States)

    Brookes, Steven J; Barron, Martin J; Dixon, Michael J; Kirkham, Jennifer

    2017-01-01

    During the secretory phase of their life-cycle, ameloblasts are highly specialized secretory cells whose role is to elaborate an extracellular matrix that ultimately confers both form and function to dental enamel, the most highly mineralized of all mammalian tissues. In common with many other "professional" secretory cells, ameloblasts employ the unfolded protein response (UPR) to help them cope with the large secretory cargo of extracellular matrix proteins transiting their ER (endoplasmic reticulum)/Golgi complex and so minimize ER stress. However, the UPR is a double-edged sword, and, in cases where ER stress is severe and prolonged, the UPR switches from pro-survival to pro-apoptotic mode. The purpose of this review is to consider the role of the ameloblast UPR in the biology and pathology of amelogenesis; specifically in respect of amelogenesis imperfecta (AI) and fluorosis. Some forms of AI appear to correspond to classic proteopathies, where pathological intra-cellular accumulations of protein tip the UPR toward apoptosis. Fluorosis also involves the UPR and, while not of itself a classic proteopathic disease, shares some common elements through the involvement of the UPR. The possibility of therapeutic intervention by pharmacological modulation of the UPR in AI and fluorosis is also discussed.

  2. 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

  3. Congenital adrenal hyperplasia with localized aggressive periodontitis and amelogenesis imperfecta.

    Science.gov (United States)

    Ajlan, Sumaiah Abdulbaqi

    2015-11-01

    Congenital adrenal hyperplasia (CAH) is an inherited medical condition that implies defects in steroid biosynthesis. The dental findings of a female patient with CAH are reported. The patient suffered from severe periodontal tissue destruction, obvious enamel defects, as well as some occlusal problems. The management approach is presented and the possibility of interrelation of her dental findings with her medical condition is discussed. © 2015 Japanese Teratology 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. Osteogenesis Imperfecta Foundation

    Science.gov (United States)

    ... Wheel Regional Conference 50,000 Laps, One Unbreakable Spirit® OI Golf Classic Awareness Week Fine Wines Strong Bones Bone China Tea Blue Jeans for Better Bones Upcoming Events Online Store What is Osteogenesis Imperfecta? Osteogenesis Imperfecta (OI) is a ...

  6. Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis.

    Science.gov (United States)

    Bardet, Claire; Ribes, Sandy; Wu, Yong; Diallo, Mamadou Tidiane; Salmon, Benjamin; Breiderhoff, Tilman; Houillier, Pascal; Müller, Dominik; Chaussain, Catherine

    2017-01-01

    Claudins are a family of proteins that forms paracellular barriers and pores determining tight junctions (TJ) permeability. Claudin-16 and -19 are pore forming TJ proteins allowing calcium and magnesium reabsorption in the thick ascending limb of Henle's loop (TAL). Loss-of-function mutations in the encoding genes, initially identified to cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC), were recently shown to be also involved in Amelogenesis Imperfecta (AI). In addition, both claudins were expressed in the murine tooth germ and Claudin-16 knockout (KO) mice displayed abnormal enamel formation. Claudin-3, an ubiquitous claudin expressed in epithelia including kidney, acts as a barrier-forming tight junction protein. We determined that, similarly to claudin-16 and claudin-19, claudin-3 was expressed in the tooth germ, more precisely in the TJ located at the apical end of secretory ameloblasts. The observation of Claudin-3 KO teeth revealed enamel defects associated to impaired TJ structure at the secretory ends of ameloblasts and accumulation of matrix proteins in the forming enamel. Thus, claudin-3 protein loss-of-function disturbs amelogenesis similarly to claudin-16 loss-of-function, highlighting the importance of claudin proteins for the TJ structure. These findings unravel that loss-of-function of either pore or barrier-forming TJ proteins leads to enamel defects. Hence, the major structural function of claudin proteins appears essential for amelogenesis.

  7. Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis

    Directory of Open Access Journals (Sweden)

    Claire Bardet

    2017-05-01

    Full Text Available Claudins are a family of proteins that forms paracellular barriers and pores determining tight junctions (TJ permeability. Claudin-16 and -19 are pore forming TJ proteins allowing calcium and magnesium reabsorption in the thick ascending limb of Henle's loop (TAL. Loss-of-function mutations in the encoding genes, initially identified to cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC, were recently shown to be also involved in Amelogenesis Imperfecta (AI. In addition, both claudins were expressed in the murine tooth germ and Claudin-16 knockout (KO mice displayed abnormal enamel formation. Claudin-3, an ubiquitous claudin expressed in epithelia including kidney, acts as a barrier-forming tight junction protein. We determined that, similarly to claudin-16 and claudin-19, claudin-3 was expressed in the tooth germ, more precisely in the TJ located at the apical end of secretory ameloblasts. The observation of Claudin-3 KO teeth revealed enamel defects associated to impaired TJ structure at the secretory ends of ameloblasts and accumulation of matrix proteins in the forming enamel. Thus, claudin-3 protein loss-of-function disturbs amelogenesis similarly to claudin-16 loss-of-function, highlighting the importance of claudin proteins for the TJ structure. These findings unravel that loss-of-function of either pore or barrier-forming TJ proteins leads to enamel defects. Hence, the major structural function of claudin proteins appears essential for amelogenesis.

  8. 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.

  9. FAM20A Gene Mutation: Amelogenesis or Ectopic Mineralization?

    Directory of Open Access Journals (Sweden)

    Guilhem Lignon

    2017-05-01

    Full Text Available Background and objective:FAM20A gene mutations result in enamel renal syndrome (ERS associated with amelogenesis imperfecta (AI, nephrocalcinosis, gingival fibromatosis, and impaired tooth eruption. FAM20A would control the phosphorylation of enamel peptides and thus enamel mineralization. Here, we characterized the structure and chemical composition of unerupted tooth enamel from ERS patients and healthy subjects.Methods: Tooth sections were analyzed by Scanning Electron Microscopy (SEM, Energy Dispersive Spectroscopy (EDS, X-Ray Diffraction (XRD, and X-Ray Fluorescence (XRF.Results: SEM revealed that prisms were restricted to the inner-most enamel zones. The bulk of the mineralized matter covering the crown was formed by layers with varying electron-densities organized into lamellae and micronodules. Tissue porosity progressively increased at the periphery, ending with loose and unfused nanonodules also observed in the adjoining soft tissues. Thus, the enamel layer covering the dentin in all ERS patients (except a limited layer of enamel at the dentino-enamel junction displayed an ultrastructural globular pattern similar to one observed in ectopic mineralization of soft tissue, notably in the gingiva of Fam20a knockout mice. XRD analysis confirmed the existence of alterations in crystallinity and composition (vs. sound enamel. XRF identified lower levels of calcium and phosphorus in ERS enamel. Finally, EDS confirmed the reduced amount of calcium in ERS enamel, which appeared similar to dentin.Conclusion: This study suggests that, after an initial normal start to amelogenesis, the bulk of the tissue covering coronal dentin would be formed by different mechanisms based on nano- to micro-nodule aggregation. This evocated ectopic mineralization process is known to intervene in several soft tissues in FAM20A gene mutant.

  10. FAM20A Gene Mutation: Amelogenesis or Ectopic Mineralization?

    Science.gov (United States)

    Lignon, Guilhem; Beres, Fleur; Quentric, Mickael; Rouzière, Stephan; Weil, Raphael; De La Dure-Molla, Muriel; Naveau, Adrien; Kozyraki, Renata; Dessombz, Arnaud; Berdal, Ariane

    2017-01-01

    Background and objective: FAM20A gene mutations result in enamel renal syndrome (ERS) associated with amelogenesis imperfecta (AI), nephrocalcinosis, gingival fibromatosis, and impaired tooth eruption. FAM20A would control the phosphorylation of enamel peptides and thus enamel mineralization. Here, we characterized the structure and chemical composition of unerupted tooth enamel from ERS patients and healthy subjects. Methods: Tooth sections were analyzed by Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-Ray Diffraction (XRD), and X-Ray Fluorescence (XRF). Results: SEM revealed that prisms were restricted to the inner-most enamel zones. The bulk of the mineralized matter covering the crown was formed by layers with varying electron-densities organized into lamellae and micronodules. Tissue porosity progressively increased at the periphery, ending with loose and unfused nanonodules also observed in the adjoining soft tissues. Thus, the enamel layer covering the dentin in all ERS patients (except a limited layer of enamel at the dentino-enamel junction) displayed an ultrastructural globular pattern similar to one observed in ectopic mineralization of soft tissue, notably in the gingiva of Fam20a knockout mice. XRD analysis confirmed the existence of alterations in crystallinity and composition (vs. sound enamel). XRF identified lower levels of calcium and phosphorus in ERS enamel. Finally, EDS confirmed the reduced amount of calcium in ERS enamel, which appeared similar to dentin. Conclusion: This study suggests that, after an initial normal start to amelogenesis, the bulk of the tissue covering coronal dentin would be formed by different mechanisms based on nano- to micro-nodule aggregation. This evocated ectopic mineralization process is known to intervene in several soft tissues in FAM20A gene mutant.

  11. Transcriptional factor DLX3 promotes the gene expression of enamel matrix proteins during amelogenesis.

    Directory of Open Access Journals (Sweden)

    Zhichun Zhang

    Full Text Available Mutation of distal-less homeobox 3 (DLX3 is responsible for human tricho-dento-osseous syndrome (TDO with amelogenesis imperfecta, indicating a crucial role of DLX3 in amelogenesis. However, the expression pattern of DLX3 and its specific function in amelogenesis remain largely unknown. The aim of this study was to investigate the effects of DLX3 on enamel matrix protein (EMP genes. By immunohistochemistry assays of mouse tooth germs, stronger immunostaining of DLX3 protein was identified in ameloblasts in the secretory stage than in the pre-secretory and maturation stages, and the same pattern was found for Dlx3 mRNA using Realtime PCR. In a mouse ameloblast cell lineage, forced expression of DLX3 up-regulated the expression of the EMP genes Amelx, Enam, Klk4, and Odam, whereas knockdown of DLX3 down-regulated these four EMP genes. Further, bioinformatics, chromatin immunoprecipitation, and luciferase assays revealed that DLX3 transactivated Enam, Amelx, and Odam through direct binding to their enhancer regions. Particularly, over-expression of mutant-DLX3 (c.571_574delGGGG, responsible for TDO inhibited the activation function of DLX3 on expression levels and promoter activities of the Enam, Amelx, and Odam genes. Together, our data show that DLX3 promotes the expression of the EMP genes Amelx, Enam, Klk4, and Odam in amelogenesis, while mutant-DLX3 disrupts this regulatory function, thus providing insights into the molecular mechanisms underlying the enamel defects of TDO disease.

  12. Osteogenesis Imperfecta Overview

    Science.gov (United States)

    ... caused by a dominant mutation in a gene coding for type 1 collagen (Types I, II, III, ... more information on OI inheritance, see the fact sheet, Genetics , from the Osteogenesis Imperfecta Foundation. Treatment There ...

  13. 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 ...

  14. Myths about OI (Osteogenesis Imperfecta)

    Science.gov (United States)

    ... Based on the OI Foundation publication Introduction to Osteogenesis Imperfecta: A Guide for Medical Professionals, Individuals and Families ... for Children, editor, 2013. Page updated August, 2015. © Osteogenesis Imperfecta Foundation, 2015 Privacy Policy

  15. 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.

  16. 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...

  17. 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 parents are unable to explain how ... the fractures is not child abuse. It is osteogenesis imperfecta , or OI. OI is a genetic disorder characterized ...

  18. Osteogenesis imperfecta in Holstein-Friesian calves

    International Nuclear Information System (INIS)

    Agerholm, J.S.; Lund, A.M.; Bloch, B.; Reibel, J.; Basse, A.; Arnbjerg, J.

    1994-01-01

    Eight calves with osteogenesis imperfecta were born in a Danish Holstein-Friesian herd during a two-year period. In total 92 calves were born (84 normal), and all were sired by a clinically normal Holstein-Friesian bull. The defect was probably due to a de novo dominant mutation present as a gonadal mosaicism in the bull. Affected calves were characterised by multiple fractures, congenital bone deformations, generaljoint laxity, dentinogenesis imperfecta, and light blue sclerae. The skin seemed normal. Electron microscopical studies revealed slightly decreased average diameter of cutaneous collagen fibrils, while the diameter of collagen fibrils in tendons and ligaments was severely reduced. Abnormalities of collagen type I from skin and compact bone were not detected by biochemical analyses

  19. 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.

  20. Pleiotropic function of DLX3 in amelogenesis: from regulating pH and keratin expression to controlling enamel rod decussation.

    Science.gov (United States)

    Duverger, Olivier; Morasso, Maria I

    2018-12-01

    DLX3 is essential for tooth enamel development and is so far the only transcription factor known to be mutated in a syndromic form of amelogenesis imperfecta. Through conditional deletion of Dlx3 in the dental epithelium in mouse, we have previously established the involvement of DLX3 in enamel pH regulation, as well as in controlling the expression of sets of keratins that contribute to enamel rod sheath formation. Here, we show that the decussation pattern of enamel rods was lost in conditional knockout animals, suggesting that DLX3 controls the coordinated migration of ameloblasts during enamel secretion. We further demonstrate that DLX3 regulates the expression of some components of myosin II complexes potentially involved in driving the movement of ameloblasts that leads to enamel rod decussation.

  1. Genetics Home Reference: osteogenesis imperfecta

    Science.gov (United States)

    ... 2008 Jul;40(7):927. Citation on PubMed Cole WG. Advances in osteogenesis imperfecta. Clin Orthop Relat ... medicine? What is newborn screening? New Pages Lyme disease Fibromyalgia White-Sutton syndrome All New & Updated Pages ...

  2. 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

  3. 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.

  4. 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…

  5. 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.

  6. Bmp2 deletion causes an amelogenesis imperfecta phenotype via regulating enamel gene expression.

    Science.gov (United States)

    Guo, Feng; Feng, Junsheng; Wang, Feng; Li, Wentong; Gao, Qingping; Chen, Zhuo; Shoff, Lisa; Donly, Kevin J; Gluhak-Heinrich, Jelica; Chun, Yong Hee Patricia; Harris, Stephen E; MacDougall, Mary; Chen, Shuo

    2015-08-01

    Although Bmp2 is essential for tooth formation, the role of Bmp2 during enamel formation remains unknown in vivo. In this study, the role of Bmp2 in regulation of enamel formation was investigated by the Bmp2 conditional knock out (Bmp2 cKO) mice. Teeth of Bmp2 cKO mice displayed severe and profound phenotypes with asymmetric and misshaped incisors as well as abrasion of incisors and molars. Scanning electron microscopy analysis showed that the enamel layer was hypoplastic and enamel lacked a typical prismatic pattern. Teeth from null mice were much more brittle as tested by shear and compressive moduli. Expression of enamel matrix protein genes, amelogenin, enamelin, and enamel-processing proteases, Mmp-20 and Klk4 was reduced in the Bmp2 cKO teeth as reflected in a reduced enamel formation. Exogenous Bmp2 up-regulated those gene expressions in mouse enamel organ epithelial cells. This result for the first time indicates Bmp2 signaling is essential for proper enamel development and mineralization in vivo. © 2015 Wiley Periodicals, Inc.

  7. 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."

  8. 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

  9. Metaphyseal bands in osteogenesis imperfecta

    International Nuclear Information System (INIS)

    Suresh, SS; Thomas, John K

    2010-01-01

    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.”

  10. 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.

  11. 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.

  12. Orthopaedic complications of osteogenesis imperfecta

    International Nuclear Information System (INIS)

    Azrak, S.; Ksyar, R.; Ben Rais, N.

    2009-01-01

    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)

  13. 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.

  14. 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)

  15. 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.

  16. 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.

  17. 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.

  18. Osteogenesis imperfecta type V, spot diagnosis

    International Nuclear Information System (INIS)

    Kozlowski, K.

    2010-01-01

    Background: The first case of Osteogenesis Imperfecta Type V in the Polish literature is reported. Case Report: Skeletal survey of an 8 year old girl with a history of multiple fractures and bilateral dislocation of radial heads was received for consultation. Conclusions: Generalised osteoporosis with multiple fractures, periosteal thickening and bilateral dislocation of the radial heads are characteristic signs of osteogenesis imperfecta Type V. The Nosology and Classification of Genetic Skeletal Disorders 2006 Revision classified Osteogenesis Imperfecta into 8 major types. Type V is recognizable on the basis of skeletal survey alone. (author)

  19. 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.

  20. 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

  1. 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

  2. Differential expression of syndecan isoforms during mouse incisor amelogenesis.

    Science.gov (United States)

    Muto, Taro; Miyoshi, Keiko; Munesue, Seiichi; Nakada, Hiroshi; Okayama, Minoru; Matsuo, Takashi; Noma, Takafumi

    2007-08-01

    Syndecans are transmembranous heparan sulfate proteoglycans (HSPGs) with covalently attached glycosaminoglycan side-chains located on the cell surface. The mammalian syndecan family is composed of four types of syndecans (syndecan-1 to -4). Syndecans interact with the intracellular cytoskeleton through the cytoplasmic domains of their core proteins and membrane proteins, extracellular enzymes, growth factors, and matrix components, through their heparan-sulfate chains, to regulate developmental processes.Here, as a first step to assess the possible roles of syndecan proteins in amelogenesis, we examined the expression patterns of all syndecan isoforms in continuously growing mouse incisors, in which we can overview major differentiation stages of amelogenesis at a glance. Understanding the expression domain of each syndecan isoform during specific developmental stages seems useful for investigating their physiological roles in amelogenesis. Immunohistochemical analysis of syndecan core proteins in the lower incisors from postnatal day 1 mice revealed spatially and temporally specific expression patterns, with syndecan-1 expressed in undifferentiated epithelial and mesenchymal cells, and syndecan-2, -3, and -4 in more differentiated cells. These findings suggest that each syndecan isoform functions distinctly during the amelogenesis of the incisors of mice.

  3. Imaging Findings in Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Matheus Dorigatti Soldatelli

    2017-09-01

    Full Text Available A 14 months -old male patient is brought to the outpatient clinic with a history of multiple bone fractures, he was born with fractures in left femur and humerus and presented 3 more fractures until the first consultation. There was no family history of genetic disorders and consanguinity. At physical examination, short stature for his age, discolored and translucent teeth, triangular face shape and bluish color of eye sclera were noticed. Initial radiographic studies of bones showed diffuse signs of osteoporosis, deformed limb bones and multiple long bone fractures with different ages. The radiograph of the skull showed small intra-sutural bones in between the cranial sutures, known as Wormian bones (figure 1. Diagnosis of osteogenesis imperfecta (OI was confirmed and treatment with cyclic sodium pamidronate was started. At 3 years old a total of ten fractures were reported on tibias, femurs and proximal left humerus. The following radiographic studies showed the “zebra stripe sign” - sclerotic growth recovery lines in the metaphysis of long bones (figures 2 and 3.  Palavras-chave: Osteogenesis imperfecta; pediatrics; radiology

  4. Cardiovascular disease in patients with osteogenesis imperfecta - a nationwide, register-based cohort study

    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...

  5. 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

  6. 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.

  7. 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.

  8. Disease: H00618 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00618 Amelogenesis imperfecta hypoplastic-hypomaturation with taurodontism (AIHHT) Amelogenesis...t trait. Mouth and dental disease DLX3 [HSA:1747] [KO:K09315] ... Amelogenesis imperfecta and trichodentoos

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

    Science.gov (United States)

    ... Issues: Type I—Understanding the Mildest Form of Osteogenesis Imperfecta Type I OI Osteogenesis imperfecta (OI) is a ... 223-0344 Toll free: 800-624-BONE (2663) Osteogenesis Imperfecta Foundation Website: http://www.oif.org The National ...

  10. 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.

  11. Ras Signaling Regulates Stem Cells and Amelogenesis in the Mouse Incisor.

    Science.gov (United States)

    Zheng, X; Goodwin, A F; Tian, H; Jheon, A H; Klein, O D

    2017-11-01

    The role of Ras signaling during tooth development is poorly understood. Ras proteins-which are activated by many upstream pathways, including receptor tyrosine kinase cascades-signal through multiple effectors, such as the mitogen-activated protein kinase (MAPK) and PI3K pathways. Here, we utilized the mouse incisor as a model to study how the MAPK and PI3K pathways regulate dental epithelial stem cells and amelogenesis. The rodent incisor-which grows continuously throughout the life of the animal due to the presence of epithelial and mesenchymal stem cells-provides a model for the study of ectodermal organ renewal and regeneration. Utilizing models of Ras dysregulation as well as inhibitors of the MAPK and PI3K pathways, we found that MAPK and PI3K regulate dental epithelial stem cell activity, transit-amplifying cell proliferation, and enamel formation in the mouse incisor.

  12. 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

  13. Dental phenotype in Jalili syndrome due to a c.1312 dupC homozygous mutation in the CNNM4 gene.

    Directory of Open Access Journals (Sweden)

    Hans U Luder

    Full Text Available Jalili syndrome denotes a recessively inherited combination of an eye disease (cone-rod dystrophy and a dental disorder (amelogenesis imperfecta, which is caused by mutations in the CNNM4 gene. Whereas the ophthalmic consequences of these mutations have been studied comprehensively, the dental phenotype has obtained less attention. A defective transport of magnesium ions by the photoreceptors of the retina is assumed to account for the progressive visual impairment. Since magnesium is also incorporated in the mineral of dental hard tissues, we hypothesized that magnesium concentrations in defective enamel resulting from mutations in CNNM4 would be abnormal, if a similar deficiency of magnesium transport also accounted for the amelogenesis imperfecta. Thus, a detailed analysis of the dental hard tissues was performed in two boys of Kosovan origin affected by Jalili syndrome. Retinal dystrophy of the patients was diagnosed by a comprehensive eye examination and full-field electroretinography. A mutational analysis revealed a c.1312 dupC homozygous mutation in CNNM4, a genetic defect which had already been identified in other Kosovan families and putatively results in loss-of-function of the protein. The evaluation of six primary teeth using light and scanning electron microscopy as well as energy-dispersive X-ray spectroscopy showed that dental enamel was thin and deficient in mineral, suggesting a hypoplastic/hypomineralized type of amelogenesis imperfecta. The reduced mineral density of enamel was accompanied by decreased amounts of calcium, but significantly elevated levels of magnesium. In dentin, however, a similar mineral deficiency was associated with reduced magnesium and normal calcium levels. It is concluded that the c.1312 dupC mutation of CNNM4 results in mineralization defects of both enamel and dentin, which are associated with significantly abnormal magnesium concentrations. Thus, we could not disprove the hypothesis that a

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. Osteogenesis imperfecta with joint contractures: Bruck syndrome

    International Nuclear Information System (INIS)

    Blacksin, M.F.; Pletcher, B.A.; David, M.

    1998-01-01

    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.)

  1. 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...

  2. PPIB mutations cause severe osteogenesis imperfecta

    NARCIS (Netherlands)

    van Dijk, Fleur S.; Nesbitt, Isabel M.; Zwikstra, Eline H.; Nikkels, Peter G. J.; Piersma, Sander R.; Fratantoni, Silvina A.; Jimenez, Connie R.; Huizer, Margriet; Morsman, Alice C.; Cobben, Jan M.; van Roij, Mirjam H. H.; Elting, Mariet W.; Verbeke, Jonathan I. M. L.; Wijnaendts, Liliane C. D.; Shaw, Nick J.; Högler, Wolfgang; McKeown, Carole; Sistermans, Erik A.; Dalton, Ann; Meijers-Heijboer, Hanne; Pals, Gerard

    2009-01-01

    Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI). CRTAP, P3H1, and cyclophilin B (CyPB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position

  3. PPIB mutations cause severe osteogenesis imperfecta.

    Science.gov (United States)

    van Dijk, Fleur S; Nesbitt, Isabel M; Zwikstra, Eline H; Nikkels, Peter G J; Piersma, Sander R; Fratantoni, Silvina A; Jimenez, Connie R; Huizer, Margriet; Morsman, Alice C; Cobben, Jan M; van Roij, Mirjam H H; Elting, Mariet W; Verbeke, Jonathan I M L; Wijnaendts, Liliane C D; Shaw, Nick J; Högler, Wolfgang; McKeown, Carole; Sistermans, Erik A; Dalton, Ann; Meijers-Heijboer, Hanne; Pals, Gerard

    2009-10-01

    Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI). CRTAP, P3H1, and cyclophilin B (CyPB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position 986 (P986) in the alpha1 chains of collagen type I. This 3-prolyl hydroxylation is decreased in patients with CRTAP and P3H1 deficiency. It was suspected that mutations in the PPIB gene encoding CyPB would also cause OI with decreased collagen 3-prolyl hydroxylation. To our knowledge we present the first two families with recessive OI caused by PPIB gene mutations. The clinical phenotype is compatible with OI Sillence type II-B/III as seen with COL1A1/2, CRTAP, and LEPRE1 mutations. The percentage of 3-hydroxylated P986 residues in patients with PPIB mutations is decreased in comparison to normal, but it is higher than in patients with CRTAP and LEPRE1 mutations. This result and the fact that CyPB is demonstrable independent of CRTAP and P3H1, along with reported decreased 3-prolyl hydroxylation due to deficiency of CRTAP lacking the catalytic hydroxylation domain and the known function of CyPB as a cis-trans isomerase, suggest that recessive OI is caused by a dysfunctional P3H1/CRTAP/CyPB complex rather than by the lack of 3-prolyl hydroxylation of a single proline residue in the alpha1 chains of collagen type I.

  4. The dynamics of DNA methylation and hydroxymethylation during amelogenesis.

    Science.gov (United States)

    Yoshioka, Hirotaka; Minamizaki, Tomoko; Yoshiko, Yuji

    2015-11-01

    Amelogenesis is a multistep process that relies on specific temporal and spatial signaling networks between the dental epithelium and mesenchymal tissues. Epigenetic modifications of key developmental genes in this process may be closely linked to a network of molecular events. However, the role of epigenetic regulation in amelogenesis remains unclear. Here, we have uncovered the spatial distributions of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) to determine epigenetic events in the mandibular incisors of mice. Immunohistochemistry and dot blotting showed that 5-hmC in ameloblasts increased from the secretory stage to the later maturation stage. We also demonstrated the distribution of 5-mC-positive ameloblasts with punctate nuclear labeling from sometime after the initiation of the secretory stage to the later maturation stage; however, dot blotting failed to detect this change. No obvious alteration of 5-mC/5-hmC staining in odontoblasts and dental pulp cells was observed. Concomitant with quantitative expression data, immunohistochemistry showed that maintenance DNA methyltransferase DNMT1 was highly expressed in immature dental epithelial cells and subsequently decreased at later stages of development. Meanwhile, de novo DNA methyltransferase Dnmt3a and Dnmt3b and DNA demethylase Tet family genes were universally expressed, except Tet1 that was highly expressed in immature dental epithelial cells. Thus, DNMT1 may sustain the undifferentiated status of dental epithelial cells through the maintenance of DNA methylation, while the hydroxylation of 5-mC may occur through the whole differentiation process by TET activity. Taken together, these data indicate that the dynamic changes of 5-mC and 5-hmC may be critical for the regulation of amelogenesis.

  5. 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.

  6. 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

  7. 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

  8. Cardiovascular disease in patients with osteogenesis imperfecta — a nationwide, register-based cohort study

    OpenAIRE

    Folkestad, Lars; Hald, Jannie Dahl; Gram, Jeppe; Langdahl, Bente L.; Hermann, Anne Pernille; Diederichsen, Axel CP; Abrahamsen, Bo; Brixen, Kim

    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.OBJECTIVE: To investigate the risk of symptomatic CVD in OI.DESIGN: A Danish nationwide, population-based and register-based longitudinal open cohort study.PARTICIPANTS: All patients registered with the diag...

  9. Osteogenesis imperfecta in combination with Graves disease

    Directory of Open Access Journals (Sweden)

    Marina S. Sheremeta

    2017-12-01

    Full Text Available Osteogenesis imperfecta (OI – is a group of genetically disorders, which are charaterized by a disturbed bone formation. In turn, the excess of thyroid hormones in Graves' disease (GD also posses a negative effect on bone tissue, thereby aggravating OI. That requires from the endocrinologist the most careful management of patients with the combination of these pathologies. In this article, we present a unique clinical case of a combination of GD and OI.

  10. 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.

  11. Quantitative electron microscopical autoradiography of calcium during amelogenesis

    International Nuclear Information System (INIS)

    Nagai, Yoshinori; Frank, R.M.

    1975-01-01

    The migration of 45 Ca through the stratum intermedium and through the secreting ameloblasts towards enamel has been studied by electron microscopical autoradiography in the toothgerms of newborn cats. A quantitative procedure was applied to the study of the 45 Ca migration in amelogenesis and two pathways were demonstrated. The relatively more important direct route passed through the stratum intermedium and the ameloblast intercellular spaces and reached the enamel directly. The second pathway consisted of an intracellular migration through the ameloblast. 45 Ca penetrated the cell through its basal pole. The mitochondrias were the most highly labeled organelles at the different experimental time intervals studied. A total absence of silver grains was noted over the secretory ameloblastic bodies. At 6 hours, the highest labeling was observed over enamel. (auth.)

  12. Structure of initial crystals formed during human amelogenesis

    Science.gov (United States)

    Cuisinier, F. J. G.; Voegel, J. C.; Yacaman, J.; Frank, R. M.

    1992-02-01

    X-ray diffraction analysis revealed only the existence of carbonated hydroxyapatite (c.HA) during amelogenesis, whereas conventional transmission electron microscopy investigations showed that developing enamel crystals have a ribbon-like habit. The described compositional changes could be an indication for the presence of minerals different from c.HA. However, the absence of identification of such a mineral shows the need of studies by high resolution electron microscopy (HREM) of initial formed human enamel crystals. We demonstrate the existence of two crystal families involved in the early stages of biomineralization: (a) nanometer-size particles which appeared as a precursor phase; (b) ribbon-like crystals, with a structure closely related to c.HA, which by a progressive thickening process tend to attain the mature enamel crystal habit.

  13. 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.

  14. Possible linkage of SP6 transcriptional activity with amelogenesis by protein stabilization.

    Science.gov (United States)

    Utami, Trianna W; Miyoshi, Keiko; Hagita, Hiroko; Yanuaryska, Ryna Dwi; Horiguchi, Taigo; Noma, Takafumi

    2011-01-01

    Ameloblasts produce enamel matrix proteins such as amelogenin, ameloblastin, and amelotin during tooth development. The molecular mechanisms of ameloblast differentiation (amelogenesis) are currently not well understood. SP6 is a transcription factor of the Sp/KLF family that was recently found to regulate cell proliferation in a cell-type-specific manner. Sp6-deficient mice demonstrate characteristic tooth anomalies such as delayed eruption of the incisors and supernumerary teeth with disorganized amelogenesis. However, it remains unclear how Sp6 controls amelogenesis. In this study, we used SP6 high producer cells to identify SP6 target genes. Based on the observations that long-term culture of SP6 high producer cells reduced SP6 protein expression but not Sp6 mRNA expression, we found that SP6 is short lived and specifically degraded through a proteasome pathway. We established an in vitro inducible SP6 expression system coupled with siRNA knockdown and found a possible linkage between SP6 and amelogenesis through the regulation of amelotin and Rock1 gene expression by microarray analysis. Our findings suggest that the regulation of SP6 protein stability is one of the crucial steps in amelogenesis.

  15. Possible Linkage of SP6 Transcriptional Activity with Amelogenesis by Protein Stabilization

    Directory of Open Access Journals (Sweden)

    Trianna W. Utami

    2011-01-01

    Full Text Available Ameloblasts produce enamel matrix proteins such as amelogenin, ameloblastin, and amelotin during tooth development. The molecular mechanisms of ameloblast differentiation (amelogenesis are currently not well understood. SP6 is a transcription factor of the Sp/KLF family that was recently found to regulate cell proliferation in a cell-type-specific manner. Sp6-deficient mice demonstrate characteristic tooth anomalies such as delayed eruption of the incisors and supernumerary teeth with disorganized amelogenesis. However, it remains unclear how Sp6 controls amelogenesis. In this study, we used SP6 high producer cells to identify SP6 target genes. Based on the observations that long-term culture of SP6 high producer cells reduced SP6 protein expression but not Sp6 mRNA expression, we found that SP6 is short lived and specifically degraded through a proteasome pathway. We established an in vitro inducible SP6 expression system coupled with siRNA knockdown and found a possible linkage between SP6 and amelogenesis through the regulation of amelotin and Rock1 gene expression by microarray analysis. Our findings suggest that the regulation of SP6 protein stability is one of the crucial steps in amelogenesis.

  16. 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.

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

    International Nuclear Information System (INIS)

    Burchardt, A.J.; Wagner, A.A.; Basse, P.

    1994-01-01

    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.)

  18. 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.).

  19. 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.

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

    African Journals Online (AJOL)

    A case of osteogenesis imperfecta type II, a diagnosis made almost too late in a resource ... Nigerian Journal of Paediatrics ... A working diagnosis of osteogenesis imperfecta type II was made and baby was placed on oxygen via face mask.

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

    Science.gov (United States)

    ... Links Key Signaling Molecule to Underlying Cause of Osteogenesis Imperfecta By Kirstie Saltsman, Ph.D. | September 5, 2014 Vertebra from a mouse engineered to have osteogenesis imperfecta (upper panel). Following eight weeks of treatment with ...

  2. Single Molecule Effects of Osteogenesis Imperfecta Mutations in Tropocollagen Protein Domains

    Science.gov (United States)

    2008-12-02

    Single molecule effects of osteogenesis imperfecta mutations in tropocollagen protein domains Alfonso Gautieri,1,2 Simone Vesentini,2 Alberto...2008 proteinscience.org Abstract: Osteogenesis imperfecta (OI) is a genetic disease characterized by fragile bones, skeletal deformities and, in severe...diagnosis and treatment, an effort referred to as materiomics. Keywords: steered molecular dynamics; osteogenesis imperfecta ; Young’s modulus; collagen

  3. The specific role of FAM20C in amelogenesis.

    Science.gov (United States)

    Wang, X; Jung, J; Liu, Y; Yuan, B; Lu, Y; Feng, J Q; Qin, C

    2013-11-01

    Previously, we showed that Sox2-Cre;Fam20C(fl/fl) mice in which Fam20C was ubiquitously inactivated had severe defects in dentin, enamel, and bone, along with hypophosphatemia. It remains to be determined if the enamel defects in the mice with universal inactivation of Family with sequence similarity 20-C (FAM20C) were associated with the dentin defects and whether hypophosphatemia in the knockout mice contributed to the enamel defects. In this study, we crossed Fam20C(fl/fl) mice with keratin 14-Cre (K14-Cre) transgenic mice to specifically inactivate Fam20C in the epithelial cells, including the dental epithelial cells that are responsible for forming tooth enamel. X-ray, backscattered scanning electron microscopic, and histological analyses showed that the K14-Cre;Fam20C(fl/fl) mice had severe enamel and ameloblast defects, while their dentin and alveolar bone were not significantly affected. Accordingly, serum biochemistry of the K14-Cre;Fam20C(fl/fl) mice showed normal phosphate and FGF23 levels in the circulation. Analysis of these data indicates that, while FAM20C is a molecule essential to amelogenesis, its inactivation in the dental epithelium does not significantly affect dentinogenesis. Hypophosphatemia makes no significant contribution to the enamel defects in the mice with the ubiquitous deletion of Fam20C.

  4. WHOLE-BODY VIBRATION EXERCISE IMPROVES FUNCTIONAL PARAMETERS IN PATIENTS WITH OSTEOGENESIS IMPERFECTA: A SYSTEMATIC REVIEW WITH A SUITABLE APPROACH

    OpenAIRE

    S?-Caputo, Danubia C; Dionello, Carla da F; Frederico, ?ric Heleno F. F; Paineiras-Domingos, Laisa L; Sousa-Gon?alves, Cintia Renata; Morel, Danielle S; Moreira-Marconi, Elo?; Unger, Marianne; Bernardo-Filho, Mario

    2017-01-01

    Background: Patients with osteogenesis imperfecta (OI) have abnormal bone modelling and resorption. The bone tissue adaptation and responsivity to dynamic and mechanical loading may be of therapeutic use under controlled circumstances. Improvements due to the wholebody vibration (WBV) exercises have been reported in strength, motion, gait, balance, posture and bone density in several osteopenic individuals, as in post-menopausal women or children with disabling conditions, as patients with OI...

  5. Comparative temporospatial expression profiling of murine amelotin protein during amelogenesis.

    Science.gov (United States)

    Somogyi-Ganss, Eszter; Nakayama, Yohei; Iwasaki, Kengo; Nakano, Yukiko; Stolf, Daiana; McKee, Marc D; Ganss, Bernhard

    2012-01-01

    Tooth enamel is formed in a typical biomineralization process under the guidance of specific organic components. Amelotin (AMTN) is a recently identified, secreted protein that is transcribed predominantly during the maturation stage of enamel formation, but its protein expression profile throughout amelogenesis has not been described in detail. The main objective of this study was to define the spatiotemporal expression profile of AMTN during tooth development in comparison with other known enamel proteins. A peptide antibody against AMTN was raised in rabbits, affinity purified and used for immunohistochemical analyses on sagittal and transverse paraffin sections of decalcified mouse hemimandibles. The localization of AMTN was compared to that of known enamel proteins amelogenin, ameloblastin, enamelin, odontogenic ameloblast-associated/amyloid in Pindborg tumors and kallikrein 4. Three-dimensional images of AMTN localization in molars at selected ages were reconstructed from serial stained sections, and transmission electron microscopy was used for ultrastructural localization of AMTN. AMTN was detected in ameloblasts of molars in a transient fashion, declining at the time of tooth eruption. Prominent expression in maturation stage ameloblasts of the continuously erupting incisor persisted into adulthood. In contrast, amelogenin, ameloblastin and enamelin were predominantly found during the early secretory stage, while odontogenic ameloblast-associated/amyloid in Pindborg tumors and kallikrein 4 expression in maturation stage ameloblasts paralleled that of AMTN. Secreted AMTN was detected at the interface between ameloblasts and the mineralized enamel. Recombinant AMTN protein did not mediate cell attachment in vitro. These results suggest a primary role for AMTN in the late stages of enamel mineralization. Copyright © 2011 S. Karger AG, Basel.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.)

  11. Pseudomass of the sternal manubrium in osteogenesis imperfecta

    International Nuclear Information System (INIS)

    Yekeler, Ensar; Kumbasar, Basak; Dursun, Memduh; Tunaci, Mehtap; Cantez, Serdar; Emiroglu, Halil Haldun

    2003-01-01

    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.)

  12. Skeletal muscle weakness in osteogenesis imperfecta mice.

    Science.gov (United States)

    Gentry, Bettina A; Ferreira, J Andries; McCambridge, Amanda J; Brown, Marybeth; Phillips, Charlotte L

    2010-09-01

    Exercise intolerance, muscle fatigue and weakness are often-reported, little-investigated concerns of patients with osteogenesis imperfecta (OI). OI is a heritable connective tissue disorder hallmarked by bone fragility resulting primarily from dominant mutations in the proα1(I) or proα2(I) collagen genes and the recently discovered recessive mutations in post-translational modifying proteins of type I collagen. In this study we examined the soleus (S), plantaris (P), gastrocnemius (G), tibialis anterior (TA) and quadriceps (Q) muscles of mice expressing mild (+/oim) and moderately severe (oim/oim) OI for evidence of inherent muscle pathology. In particular, muscle weight, fiber cross-sectional area (CSA), fiber type, fiber histomorphology, fibrillar collagen content, absolute, relative and specific peak tetanic force (P(o), P(o)/mg and P(o)/CSA respectively) of individual muscles were evaluated. Oim/oim mouse muscles were generally smaller, contained less fibrillar collagen, had decreased P(o) and an inability to sustain P(o) for the 300-ms testing duration for specific muscles; +/oim mice had a similar but milder skeletal muscle phenotype. +/oim mice had mild weakness of specific muscles but were less affected than their oim/oim counterparts which demonstrated readily apparent skeletal muscle pathology. Therefore muscle weakness in oim mice reflects inherent skeletal muscle pathology. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Physical training in children with osteogenesis imperfecta.

    Science.gov (United States)

    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 or care as usual for 3 months. Exercise capacity and muscle force were studied; subjective fatigue, perceived competence, and health-related quality of life were secondary outcomes. All outcomes were measured at baseline (T = 0), after intervention (T = 1), and after 6 and 9 months (T = 2 and T = 3, respectively). After intervention (T = 1), peak oxygen consumption (VO2peak), relative VO2peak (VO2peak/kg), maximal working capacity (Wmax), and muscle force were significantly improved (17%, 18%, 10%, and 12%, respectively) compared with control values. Subjective fatigue decreased borderline statistically significantly. Follow-up at T = 2 showed a significant decrease of the improvements measured at T = 1 of VO2peak, but VO2peak/kg, Wmax, and subjective fatigue showed no significant difference. At T = 3, we found a further decrease of the gained improvements. A supervised training program can improve aerobic capacity and muscle force and reduces levels of subjective fatigue in children with OI type I and IV in a safe and effective manner.

  14. 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

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

    NARCIS (Netherlands)

    Janus, G. J. M.; Engelbert, R. H. H.; Beek, E.; Gooskens, R. H. J. M.; Pruijs, J. E. H.

    2003-01-01

    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). In a cohort study of 130 patients with

  16. 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...

  17. Radiation therapy of hyperplastic heterotopic ossifications in osteogenesis imperfecta

    International Nuclear Information System (INIS)

    Micke, O.; Wagner, W.; Poetter, R.; Prott, F.J.; Karbowski, A.

    1994-01-01

    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.) [de

  18. 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

    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

  19. 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...

  20. 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...

  1. Wormian bones in osteogenesis imperfecta and other disorders

    International Nuclear Information System (INIS)

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

    1982-01-01

    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. (orig.)

  2. CRANIOFACIAL MORPHOLOGY AND DENTAL OCCLUSION IN ADULTS WITH OSTEOGENESIS IMPERFECTA

    DEFF Research Database (Denmark)

    Gjørup, Hans; Hald, Jannie Dahl; Harsløf, Torben

    AIMS: To compare craniofacial characteristics and variation in dental occlusion according to severity of osteogenesis imperfecta (OI). OI is a rare inherited disease with fragility of bone and teeth because of abnormalities in the formation of collagen. METHODS: A total of 73 patients...

  3. 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.

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

    DEFF Research Database (Denmark)

    Folkestad, Lars

    2018-01-01

    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...

  5. 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

  6. [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.

  7. 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.

  8. GEP, a local growth factor, is critical for odontogenesis and amelogenesis.

    Science.gov (United States)

    Cao, Zhengguo; Jiang, Baichun; Xie, Yixia; Liu, Chuan-ju; Feng, Jian Q

    2010-11-25

    Granulin epithelin precursor (GEP) is a new growth factor that functions in brain development, chondrogenesis, tissue regeneration, tumorigenesis, and inflammation. The goal of this study was to study whether GEP was critical for odontogenesis and amelogenesis both in vivo and in vitro. The in situ hybridization and immunohistochemistry data showed that GEP was expressed in both odontoblast and ameloblast cells postnatally. Knockdown of GEP by crossing U6-ploxPneo-GEP and Sox2-Cre transgenic mice led to a reduction of dentin thickness, an increase in predentin thickness, and a reduction in mineral content in enamel. The in vitro application of recombinant GEP up-regulated molecular markers important for odontogenesis (DMP1, DSPP, and ALP) and amelogenesis (ameloblastin, amelogenin and enamelin). In conclusion, both the in vivo and the in vivo data support an important role of GEP in tooth formation during postnatal development.

  9. Radiation effect on the stages of amelogenesis in the rat incisor

    International Nuclear Information System (INIS)

    Choi, Hyun Bae; Choi, Soon Chul; Park, Tae Won; You, Dong Soo

    1997-01-01

    The purpose of this study was to investigate the radiation effect on the stages of amelogenesis. Twenty 11-day-old rats which were irradiated by 4 GY of gamma radiation on the 19th prenatal day were used for the experimental group and twenty 11-day-old rats which were not irradiated were used for the control group. The length of each zone of amelogenesis were measured on the sagittal section using a light microscopic enlargement at 400X the normal view while the morphologic changes of ameloblasts of each zone were observed electron-microscopically. The obtained results were as followed : 1. The length of the region of facing pulp and facing dentin of the zone of presecretion were increased by 11.5% (P 0.01). 3. The total length of the zone of amelogenesis was not changed significantly (P>0.05). 4. Electron-microscopically, enlargement of the cell membrane, rER, mitochondria, and nuclear membrane were observed. These changes were mostly severe in the zone of maturation.

  10. Stable Isotopes Reveal Rapid Enamel Elongation (Amelogenesis) Rates for the Early Cretaceous Iguanodontian Dinosaur Lanzhousaurus magnidens.

    Science.gov (United States)

    Suarez, Celina A; You, Hai-Lu; Suarez, Marina B; Li, Da-Qing; Trieschmann, J B

    2017-11-10

    Lanzhousaurus magnidens, a large non-hadrosauriform iguanodontian dinosaur from the Lower Cretaceous Hekou Group of Gansu Province, China has the largest known herbivorous dinosaur teeth. Unlike its hadrosauriform relatives possessing tooth batteries of many small teeth, Lanzhousaurus utilized a small number (14) of very large teeth (~10 cm long) to create a large, continuous surface for mastication. Here we investigate the significance of Lanzhousaurus in the evolutionary history of iguanodontian-hadrosauriform transition by using a combination of stable isotope analysis and CT imagery. We infer that Lanzhousaurus had a rapid rate of tooth enamel elongation or amelogenesis at 0.24 mm/day with dental tissues common to other Iguanodontian dinosaurs. Among ornithopods, high rates of amelogenesis have been previously observed in hadrosaurids, where they have been associated with a sophisticated masticatory apparatus. These data suggest rapid amelogenesis evolved among non-hadrosauriform iguanodontians such as Lanzhousaurus, representing a crucial step that was exapted for the evolution of the hadrosaurian feeding mechanism.

  11. Radiation effect on the stages of amelogenesis in the rat incisor

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hyun Bae; Choi, Soon Chul; Park, Tae Won; You, Dong Soo [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1997-02-15

    The purpose of this study was to investigate the radiation effect on the stages of amelogenesis. Twenty 11-day-old rats which were irradiated by 4 GY of gamma radiation on the 19th prenatal day were used for the experimental group and twenty 11-day-old rats which were not irradiated were used for the control group. The length of each zone of amelogenesis were measured on the sagittal section using a light microscopic enlargement at 400X the normal view while the morphologic changes of ameloblasts of each zone were observed electron-microscopically. The obtained results were as followed : 1. The length of the region of facing pulp and facing dentin of the zone of presecretion were increased by 11.5% (P<0.01) and 17.7% (P<0.01), respectively. 2. The length of the zone of secretion was increased by 17.3% (P<0.01), but the zone of maturation was decreased by 15.3% (P>0.01). 3. The total length of the zone of amelogenesis was not changed significantly (P>0.05). 4. Electron-microscopically, enlargement of the cell membrane, rER, mitochondria, and nuclear membrane were observed. These changes were mostly severe in the zone of maturation.

  12. 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

  13. 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…

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

    International Nuclear Information System (INIS)

    Rieker, O.; Kreitner, K.F.; Karbowski, A.

    1998-01-01

    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.)

  15. 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.

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

    OpenAIRE

    Mehtap Çakır; Mine Öztürk

    2011-01-01

    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-ol...

  17. 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.

  18. 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.

  19. Severe Osteogenesis Imperfecta in Cyclophilin B–Deficient Mice

    Science.gov (United States)

    Choi, Jae Won; Sutor, Shari L.; Lindquist, Lonn; Evans, Glenda L.; Madden, Benjamin J.; Bergen, H. Robert; Hefferan, Theresa E.; Yaszemski, Michael J.; Bram, Richard J.

    2009-01-01

    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. PMID:19997487

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

    Science.gov (United States)

    Choi, Jae Won; Sutor, Shari L; Lindquist, Lonn; Evans, Glenda L; Madden, Benjamin J; Bergen, H Robert; Hefferan, Theresa E; Yaszemski, Michael J; Bram, Richard J

    2009-12-01

    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.

  1. Severe early onset retinitis pigmentosa in a Moroccan patient with Heimler syndrome due to novel homozygous mutation of PEX1 gene.

    Science.gov (United States)

    Ratbi, Ilham; Jaouad, Imane Cherkaoui; Elorch, Hamza; Al-Sheqaih, Nada; Elalloussi, Mustapha; Lyahyai, Jaber; Berraho, Amina; Newman, William G; Sefiani, Abdelaziz

    2016-10-01

    Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. It is the mildest form known to date of peroxisome biogenesis disorder caused by hypomorphic mutations of PEX1 and PEX6 genes. We report on a second Moroccan family with Heimler syndrome with early onset, severe visual impairment and important phenotypic overlap with Usher syndrome. The patient carried a novel homozygous missense variant c.3140T > C (p.Leu1047Pro) of PEX1 gene. As standard biochemical screening of blood for evidence of a peroxisomal disorder did not provide a diagnosis in the individuals with HS, patients with SNHL and retinal pigmentation should have mutation analysis of PEX1 and PEX6 genes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

    International Nuclear Information System (INIS)

    Kaissi, Ali Al; Klaushofer, Klaus; Grill, Franz

    2010-01-01

    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)

  3. 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)

  4. 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.

  5. 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.

  6. 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.

  7. The overview of channels, transporters, and calcium signaling molecules during amelogenesis.

    Science.gov (United States)

    Kim, Hee-Eun; Hong, Jeong Hee

    2018-05-20

    Enamel is a highly calcified tissue. Its formation requires a progressive and dynamic system for the regulation of electrolyte concentration by enamel epithelia. A critical function of enamel epithelial cells, ameloblasts, is the secretion and movement of electrolytes via various channels and transporters to develop the enamel tissue. Enamel formation generates protons, which need to be neutralised. Thus, ameloblasts possess a buffering system to sustain mineral accretion. Normal tooth formation involves stage-dependent net fluctuations in pH during amelogenesis. To date, all of our information about ion transporters in dental enamel tissue is based solely on immunostaining-expression techniques. This review critically evaluates the current understanding and recent discoveries and physiological role of ion channels and transporters, Mg 2+ transporters, and Ca 2+ regulatory proteins during amelogenesis in enamel formation. The ways in which ameloblasts modulate ions are discussed in the context of current research for developing a novel morphologic-functional model of enamel maturation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. The Role of Epithelial Stat3 in Amelogenesis during Mouse Incisor Renewal.

    Science.gov (United States)

    Zhang, Bin; Meng, Bo; Viloria, Edward; Naveau, Adrien; Ganss, Bernhard; Jheon, Andrew H

    2018-03-16

    The aim of this study was to evaluate the role of epithelial signal transducer and activator of transcription 3 (STAT3) in mouse incisor amelogenesis. Since Stat3 is expressed in the epithelial component of developing and adult mouse teeth, we generated and analyzed Krt14Cre/+;Stat3fl/fl mutant mice in which Stat3 was inactivated in epithelia including ameloblast progenitors and ameloblasts, the cells responsible for enamel formation. Histological analysis showed little enamel matrix in mutant incisors compared to controls. Delayed incisor enamel mineralization was demonstrated using micro-computed X-ray tomography analysis and was supported by an increase in the pre-expression distance of enamel-enriched proteins such as amelogenin, ameloblastin, and kallikrein-4. Lastly, scanning electron microscopy analysis showed little enamel mineralization in mutant incisors underneath the mesial root of the 1st molar; however, the micro-architecture of enamel mineralization was similar in the erupted portion of control and mutant incisors. Taken together, our findings demonstrate for the first time that the absence of epithelial Stat3 in mice leads to delayed incisor amelogenesis. © 2018 S. Karger AG, Basel.

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

    Directory of Open Access Journals (Sweden)

    Elena Monti

    2010-08-01

    Full Text Available Elena Monti1, Monica Mottes1, Paolo Fraschini2, PierCarlo Brunelli3, Antonella Forlino4, Giacomo Venturi1, Francesco Doro1, Silvia Perlini1, Paolo Cavarzere1, Franco Antoniazzi11Department of Life Sciences and Reproduction, Pediatric Clinic University of Verona, Verona, Italy; 2Istituto Di Ricovero e Cura a Carattere Scientifico, ‘E. Medea’, Associazione La Nostra Famiglia, Bosisio Parini (LC, Italy; 3Divisione di Ortopedia Pediatrica, Spedali Civili, Brescia, Italy; 4Department of Biochemistry “A. Castellani”, University of Pavia, ItalyAbstract: 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.Keywords: osteogenesis imperfecta, bone genetic disorder, bone brittleness, “brittle bone disease”, connective tissue malfunction, short

  10. 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)

  11. 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....

  12. 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.

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

    International Nuclear Information System (INIS)

    Ziyeh, S.; Berger, R.; Reisner, K.

    2000-01-01

    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.)

  14. 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.

  15. 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.)

  16. 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.

  17. 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.

  18. WHOLE-BODY VIBRATION EXERCISE IMPROVES FUNCTIONAL PARAMETERS IN PATIENTS WITH OSTEOGENESIS IMPERFECTA: A SYSTEMATIC REVIEW WITH A SUITABLE APPROACH.

    Science.gov (United States)

    Sá-Caputo, Danubia C; Dionello, Carla da F; Frederico, Éric Heleno F F; Paineiras-Domingos, Laisa L; Sousa-Gonçalves, Cintia Renata; Morel, Danielle S; Moreira-Marconi, Eloá; Unger, Marianne; Bernardo-Filho, Mario

    2017-01-01

    Patients with osteogenesis imperfecta (OI) have abnormal bone modelling and resorption. The bone tissue adaptation and responsivity to dynamic and mechanical loading may be of therapeutic use under controlled circumstances. Improvements due to the wholebody vibration (WBV) exercises have been reported in strength, motion, gait, balance, posture and bone density in several osteopenic individuals, as in post-menopausal women or children with disabling conditions, as patients with OI. The aim of this investigation was to systematically analyse the current available literature to determine the effect of WBV exercises on functional parameters of OI patients. Three reviewers independently accessed bibliographical databases. Searches were performed in the PubMed, Scopus, Science Direct and PEDro databases using keywords related to possible interventions (including WBV) used in the management of patients with osteogenesis imperfecta . Three eligible studies were identified by searches in the analysed databases. It was concluded that WBV exercises could be an important option in the management of OI patients improving the mobility and functional parameters. However, further studies are necessary for establishing suitable protocols for these patients.

  19. 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

  20. 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.

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

    International Nuclear Information System (INIS)

    Dobrocky, I.; Seidl, G.; Grill, F.

    1999-01-01

    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.)

  2. 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.

  3. 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.)

  4. Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding.

    Science.gov (United States)

    Barnes, Aileen M; Carter, Erin M; Cabral, Wayne A; Weis, MaryAnn; Chang, Weizhong; Makareeva, Elena; Leikin, Sergey; Rotimi, Charles N; Eyre, David R; Raggio, Cathleen L; Marini, Joan C

    2010-02-11

    Osteogenesis imperfecta is a heritable disorder that causes bone fragility. Mutations in type I collagen result in autosomal dominant osteogenesis imperfecta, whereas mutations in either of two components of the collagen prolyl 3-hydroxylation complex (cartilage-associated protein [CRTAP] and prolyl 3-hydroxylase 1 [P3H1]) cause autosomal recessive osteogenesis imperfecta with rhizomelia (shortening of proximal segments of upper and lower limbs) and delayed collagen folding. We identified two siblings who had recessive osteogenesis imperfecta without rhizomelia. They had a homozygous start-codon mutation in the peptidyl-prolyl isomerase B gene (PPIB), which results in a lack of cyclophilin B (CyPB), the third component of the complex. The proband's collagen had normal collagen folding and normal prolyl 3-hydroxylation, suggesting that CyPB is not the exclusive peptidyl-prolyl cis-trans isomerase that catalyzes the rate-limiting step in collagen folding, as is currently thought. 2010 Massachusetts Medical Society

  5. 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

  6. 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),

  7. 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.

  8. Genome-wide analysis of miRNA and mRNA transcriptomes during amelogenesis.

    Science.gov (United States)

    Yin, Kaifeng; Hacia, Joseph G; Zhong, Zhe; Paine, Michael L

    2014-11-19

    In the rodent incisor during amelogenesis, as ameloblast cells transition from secretory stage to maturation stage, their morphology and transcriptome profiles change dramatically. Prior whole genome transcriptome analysis has given a broad picture of the molecular activities dominating both stages of amelogenesis, but this type of analysis has not included miRNA transcript profiling. In this study, we set out to document which miRNAs and corresponding target genes change significantly as ameloblasts transition from secretory- to maturation-stage amelogenesis. Total RNA samples from both secretory- and maturation-stage rat enamel organs were subjected to genome-wide miRNA and mRNA transcript profiling. We identified 59 miRNAs that were differentially expressed at the maturation stage relative to the secretory stage of enamel development (False Discovery Rate (FDR)<0.05, fold change (FC)≥1.8). In parallel, transcriptome profiling experiments identified 1,729 mRNA transcripts that were differentially expressed in the maturation stage compared to the secretory stage (FDR<0.05, FC≥1.8). Based on bioinformatics analyses, 5.8% (629 total) of these differentially expressed genes (DEGS) were highlighted as being the potential targets of 59 miRNAs that were differentially expressed in the opposite direction, in the same tissue samples. Although the number of predicted target DEGs was not higher than baseline expectations generated by examination of stably expressed miRNAs, Gene Ontology (GO) analysis showed that these 629 DEGS were enriched for ion transport, pH regulation, calcium handling, endocytotic, and apoptotic activities. Seven differentially expressed miRNAs (miR-21, miR-31, miR-488, miR-153, miR-135b, miR-135a and miR298) in secretory- and/or maturation-stage enamel organs were confirmed by in situ hybridization. Further, we used luciferase reporter assays to provide evidence that two of these differentially expressed miRNAs, miR-153 and miR-31, are potential

  9. 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.

  10. 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

  11. 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.

  12. Surgical treatment in Osteogenesis Imperfecta – 10 years experience

    Science.gov (United States)

    Georgescu, I; Vlad, C; Gavriliu, TȘ; Dan, S; Pârvan, AA

    2013-01-01

    Introduction. Osteogenesis imperfecta (OI) is a very rare disease compared to other afflictions, running the risk of social isolation for children and their parents, due to the problems specific to the disease. All the social, psychological and physical disadvantages must be removed or at least mitigated, all within the society’s limited resources. In Romania, this situation has led in the last couple of years to the selection of a number of extremely severe cases, which could not be solved by orthopedic and classic surgical treatment methods. These patients exhibit gracile long bones, which are distorted, often with cystic degeneration at the level of the extremities, pseudarthroses, limb length discrepancies, most of them being unable to walk, being condemned to sitting in a wheelchair. Aim. This paper deals with the experience of the Orthopedics Department of "Maria Sklodowska Curie" Clinical Emergency Hospital for Children, in Bucharest, in the field of surgical treatment for moderate and severe forms of OI, within the time frame of May 2002-May 2012. For the first time in Romania, on May 20, 2002, the team led by Professor Gh. Burnei, MD, has implanted telescopic rods in the femur and tibia of a patient with OI. One of the most important themes, of great interest in the orthopedic surgery, is the osteoarticular regularization and reconstruction in severe forms of OI, which should allow the patients to stand and walk. These cases are a challenge for the surgeon, who is in the position of applying new, complex procedures, or perfecting, modifying and adapting techniques that have already been established. The aim of the surgical treatment is the increase of the quality of life of these children and adolescents and of their social integration. Methods and results. In the above-mentioned period, from the OI patients who are in the evidence of our clinic, 32 were operated on, totaling 81 surgeries. Out of these, 28 patients, aged 2-27 years, have benefited from

  13. Surgical treatment in Osteogenesis Imperfecta - 10 years experience.

    Science.gov (United States)

    Georgescu, I; Vlad, C; Gavriliu, T Ş; Dan, S; Pârvan, A A

    2013-06-15

    Osteogenesis imperfecta (OI) is a very rare disease compared to other afflictions, running the risk of social isolation for children and their parents, due to the problems specific to the disease. All the social, psychological and physical disadvantages must be removed or at least mitigated, all within the society's limited resources. In Romania, this situation has led in the last couple of years to the selection of a number of extremely severe cases, which could not be solved by orthopedic and classic surgical treatment methods. These patients exhibit gracile long bones, which are distorted, often with cystic degeneration at the level of the extremities, pseudarthroses, limb length discrepancies, most of them being unable to walk, being condemned to sitting in a wheelchair. This paper deals with the experience of the Orthopedics Department of "Maria Sklodowska Curie" Clinical Emergency Hospital for Children, in Bucharest, in the field of surgical treatment for moderate and severe forms of OI, within the time frame of May 2002-May 2012. For the first time in Romania, on May 20, 2002, the team led by Professor Gh. Burnei, MD, has implanted telescopic rods in the femur and tibia of a patient with OI. One of the most important themes, of great interest in the orthopedic surgery, is the osteoarticular regularization and reconstruction in severe forms of OI, which should allow the patients to stand and walk. These cases are a challenge for the surgeon, who is in the position of applying new, complex procedures, or perfecting, modifying and adapting techniques that have already been established. The aim of the surgical treatment is the increase of the quality of life of these children and adolescents and of their social integration. In the above-mentioned period, from the OI patients who are in the evidence of our clinic, 32 were operated on, totaling 81 surgeries. Out of these, 28 patients, aged 2-27 years, have benefited from reconstructive surgery of the pelvic limbs

  14. 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.

  15. Osteogenesis imperfecta with ectopic mineralizations in dentin and cementum and a COL1A2 mutation.

    Science.gov (United States)

    Kantaputra, Piranit Nik; Sirirungruangsarn, Yuddhasert; Intachai, Worrachet; Ngamphiw, Chumpol; Tongsima, Sissades; Dejkhamron, Prapai

    2018-04-10

    We report a Thai father (patient 1) and his daughter (patient 2) affected with osteogenesis imperfecta type IV and dentinogenesis imperfecta. Both were heterozygous for the c.1451G>A (p.Gly484Glu) mutation in COL1A2. The father, a Thai boxer, had very mild osteogenesis imperfecta with no history of low-trauma bone fractures. Scanning electron micrography of the primary teeth with DI of the patient 2, and the primary teeth with DI of another OI patient with OI showed newly recognized dental manifestations of teeth with DI. Normal dentin and cementum might have small areas of ectopic mineralizations. Teeth affected with DI have well-organized ectopic mineralizations in dentin and cementum. The "French-fries-appearance" of the crystals at the cemento-dentinal junction and abnormal cementum have never been reported to be associated with dentinogenesis imperfecta, either isolated or osteogenesis imperfecta-associated. Our study shows for the first time that abnormal collagen fibers can lead to ectopic mineralization in dentin and cementum and abnormal cementum can be a part of osteogenesis imperfecta.

  16. Androgen Receptor Involvement in Rat Amelogenesis: An Additional Way for Endocrine-Disrupting Chemicals to Affect Enamel Synthesis.

    Science.gov (United States)

    Jedeon, Katia; Loiodice, Sophia; Salhi, Khaled; Le Normand, Manon; Houari, Sophia; Chaloyard, Jessica; Berdal, Ariane; Babajko, Sylvie

    2016-11-01

    Endocrine-disrupting chemicals (EDCs) that interfere with the steroid axis can affect amelogenesis, leading to enamel hypomineralization similar to that of molar incisor hypomineralization, a recently described enamel disease. We investigated the sex steroid receptors that may mediate the effects of EDCs during rat amelogenesis. The expression of androgen receptor (AR), estrogen receptor (ER)-α, and progesterone receptor was dependent on the stage of ameloblast differentiation, whereas ERβ remained undetectable. AR was the only receptor selectively expressed in ameloblasts involved in final enamel mineralization. AR nuclear translocation and induction of androgen-responsive element-containing promoter activity upon T treatment, demonstrated ameloblast responsiveness to androgens. T regulated the expression of genes involved in enamel mineralization such as KLK4, amelotin, SLC26A4, and SLC5A8 but not the expression of genes encoding matrix proteins, which determine enamel thickness. Vinclozolin and to a lesser extent bisphenol A, two antiandrogenic EDCs that cause enamel defects, counteracted the actions of T. In conclusion, we show, for the first time, the following: 1) ameloblasts express AR; 2) the androgen signaling pathway is involved in the enamel mineralization process; and 3) EDCs with antiandrogenic effects inhibit AR activity and preferentially affect amelogenesis in male rats. Their action, through the AR pathway, may specifically and irreversibly affect enamel, potentially leading to the use of dental defects as a biomarker of exposure to environmental pollutants. These results are consistent with the steroid hormones affecting ameloblasts, raising the issue of the hormonal influence on amelogenesis and possible sexual dimorphism in enamel quality.

  17. Mutant Runx2 regulates amelogenesis and osteogenesis through a miR-185-5p-Dlx2 axis.

    Science.gov (United States)

    Chang, Huaiguang; Wang, Yue; Liu, Haochen; Nan, Xu; Wong, Singwai; Peng, Saihui; Gu, Yajuan; Zhao, Hongshan; Feng, Hailan

    2017-12-14

    Regulation of microRNAs (miRNA) has been extensively investigated in diseases; however, little is known about the roles of miRNAs in cleidocranial dysplasia (CCD). The aim of the present study was to investigate the potential involvement of miRNAs in CCD. In vitro site-directed mutagenesis was performed to construct three mutant Runx2 expression vectors, which were then transfected into LS8 cells and MC3T3-E1 cells, to determine the impact on amelogenesis and osteogenesis, respectively. miRCURY LNA miRNA microarray identify miR-185-5p as a miRNA target commonly induced by all three Runx2 mutants. Real-time quantitative PCR was applied to determine the expression of miR-185-5p and Dlx2 in samples. Dual-luciferase reporter assays were conducted to confirm Dlx2 as a legitimate target of miR-185-5p. The suppressive effect of miR-185-5p on amelogenesis and osteogenesis of miR-185-5p was evaluated by RT-PCR and western blot examination of Amelx, Enam, Klk4, and Mmp20 gene and protein expression, and by Alizarin Red stain. We found that mutant Runx2 suppressed amelogenesis and osteogenesis. miR-185-5p, induced by Runx2, suppressed amelogenesis and osteogenesis. Furthermore, we identified Dlx2 as direct target of miR-185-5p. Consistently, Dlx2 expression was inversely correlated with miR-185-5p levels. This study highlights the molecular etiology and significance of miR-185-5p in CCD, and suggests that targeting miR-185-5p may represent a new therapeutic strategy in prevention or intervention of CCD.

  18. Effect of Intravenous Pamidronate Treatment in Children with Osteogenesis Imperfecta

    International Nuclear Information System (INIS)

    Atta, I.; Iqbal, F.; Lone, S. W.; Ibrahim, M.; Khan, Y. N.; Raza, J.

    2014-01-01

    Objective: To assess the beneficial effect of intravenous pamidronate treatment in children with osteogenesis imperfecta (OI). Study Design: Experimental study. Place and Duration of Study: Endocrine Unit at the National Institute of Child Health, Karachi, Pakistan, from January 2007 to December 2011. Methodology: All children diagnosed with osteogenesis imperfecta on the basis of repeated spontaneous fractures and typical radiological findings registered during the study period, were included in this study. Pamidronate therapy were offered to those with more than 3 fractures per year or had platyspondyly. Pamidronate disodium was diluted in isotonic saline and administered by slow ravenous infusion over 3 hours in a dosage 1 mg/kg/day for 3 consecutive days 3 monthly for 2 years. Fracture rate, bone mineral density (BMD), mobility score, wellbeing and pain episodes were evaluated at baseline and 2 years after the treatment. Good response was defined as less than 2 fractures per year or mobility score improvement and poor response as more than 2 fracture per year with mobility score less than 2. Results: Seventy two patients were included in this study. There were 40 boys and 32 girls with mean age of 3.64 +- 3.2 years. The annual fracture rate decreased overall from 5.8 +- 1.61 to 0.6 +- 0.93 (p < 0.001). BMD Z-score improved from -5.3 +- 1.74 to -1.7 +- 0.72 (p < 0.001). Mobility score was 0.94 +- 1.30 at baseline and 2.5 +- 1.02 at the end of the treatment (p < 0.001). Wellbeing gained from 3.63 +- 1.44 to 7.8 +- 1.18 (p < 0.001) and pain episode improved from 24.1 +- 8.15 to 2.7 +- 8.31 (p < 0.001). Good response was noted in 92% of patients and poor response in 8% patients. Conclusion: Bisphosphonate seems to be an effective symptomatic treatment for children with osteogenesis imperfecta irrespective of severity of mutation or clinical phenotype. Cyclical bisphosphonate therapy has a positive effect on fracture rate, BMD, mobility score, wellbeing and pain

  19. 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

  20. 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

  1. Comprehensive rehabilitation of the child with osteogenesis imperfecta.

    Science.gov (United States)

    Binder, H; Conway, A; Hason, S; Gerber, L H; Marini, J; Berry, R; Weintrob, J

    1993-01-15

    Children with osteogenesis imperfecta (OI) that results in considerable deformity are often viewed as poor candidates for aggressive physical therapy and rehabilitation. To determine if this view is realistic, we have entered almost 50 children with OI type III and OI type IV into a comprehensive graduated rehabilitation program, based at the National Institutes of Health, but designed to be implemented by continuing involvement of community resources. Children are begun in the program early with emphasis on gain of head and trunk control and progression to sitting and walking, if possible, with the aid of a variety of physical supports, including internal and external bracing. Although not conducted in a randomized fashion, the program's success in bringing children into graded exercise regimes and fostering their increased involvement in school and social situations suggest that aggressive physical therapy and rehabilitation have a major place in the overall care of the infants and children with OI.

  2. 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.

  3. 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

  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. Multi-element analysis of bone from the osteogenesis imperfecta model (OIM) mouse using thermal and fast neutron activation analysis

    International Nuclear Information System (INIS)

    Huntington, C.E.; Morris, J.S.; Carleton, S.M.; McBride, D.J.; Phillips, C.L.

    2008-01-01

    Osteogenesis imperfecta (OI) is a heritable osteoporotic bone disease, due to defects in either type I procollagen genes (COL1A1 or COL1A2), resulting in abnormal and/or reduced levels of type I procollagen and alterations in bone mineralization. Our long term objectives are to evaluate the impact of proα1(I) and proα2(I) collagen mutations and the role of the genetic background on bone mineralization. Tibias from wildtype, heterozygous (oim/+), and homozygous (oim/oim) animals were subjected to instrumental neutron activation analysis (INAA) to measure F, P, Na, Mg, Cl, Ca, K, and Zn using the University of Missouri Research Reactor (MURR) pneumatic-tube irradiation facility. (author)

  6. 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.

  7. 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 

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  9. [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.

  10. 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.

  11. In-toeing in children with type I osteogenesis imperfecta: an observational descriptive study.

    Science.gov (United States)

    Losa Iglesias, Marta Elena; Becerro de Bengoa Vallejo, Ricardo; Salvadores Fuentes, Paloma

    2009-01-01

    Osteogenesis imperfecta is an autosomal-dominant disorder of the connective tissue. Also known as brittle bone disease, it renders those affected susceptible to fractures after minimal trauma. Therefore, it is important to minimize the risk of falls and subsequent fractures in patients with this disease. In-toeing is a common condition in children that can result from various pathologic entities, including anteversion, internal tibial torsion, and metatarsus adductus. These conditions can result in frequent tripping and other functional problems. A descriptive study was undertaken to determine the prevalence of in-toeing gait attributable to tibial or femoral torsion or metatarsus adductus in children with type I osteogenesis imperfecta. The study involved orthopedic and biomechanical examination of 15 children (9 girls and 6 boys) aged 4 to 9 years with confirmed type I osteogenesis imperfecta. Patients who used assistive ambulatory devices, such as canes, crutches, and wheelchairs, were excluded from the study. Of the 15 children studied, 12 (80%) demonstrated previously undiagnosed in-toeing gait attributable to torsional deformity or metatarsus adductus in all but one child. Many children with confirmed type I osteogenesis imperfecta have in-toeing gait caused by torsional deformity or metatarsus adductus. Detection and control of in-toeing gait in children with osteogenesis imperfecta is important to prevent fractures resulting from trauma directly related to these conditions.

  12. 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.

  13. 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.

  14. 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.

  15. Buffering of protons released by mineral formation during amelogenesis in mice.

    Science.gov (United States)

    Bronckers, Antonius L J J; Lyaruu, Don M; Jalali, Rozita; DenBesten, Pamela K

    2016-10-01

    Regulation of pH by ameloblasts during amelogenesis is critical for enamel mineralization. We examined the effects of reduced bicarbonate secretion and the presence or absence of amelogenins on ameloblast modulation and enamel mineralization. To that end, the composition of fluorotic and non-fluorotic enamel of several different mouse mutants, including enamel of cystic fibrosis transmembrane conductance regulator-deficient (Cftr null), anion exchanger-2-deficient (Ae2a,b null), and amelogenin-deficient (Amelx null) mice, was determined by quantitative X-ray microanalysis. Correlation analysis was carried out to compare the effects of changes in the levels of sulfated-matrix (S) and chlorine (Cl; for bicarbonate secretion) on mineralization and modulation. The chloride (Cl - ) levels in forming enamel determined the ability of ameloblasts to modulate, remove matrix, and mineralize enamel. In general, the lower the Cl - content, the stronger the negative effects. In Amelx-null mice, modulation was essentially normal and the calcium content was reduced least. Retention of amelogenins in enamel of kallikrein-4-deficient (Klk4-null) mice resulted in decreased mineralization and reduced the length of the first acid modulation band without changing the total length of all acidic bands. These data suggest that buffering by bicarbonates is critical for modulation, matrix removal and enamel mineralization. Amelogenins also act as a buffer but are not critical for modulation. © 2016 Eur J Oral Sci.

  16. Importance of bicarbonate transport in pH control during amelogenesis - need for functional studies.

    Science.gov (United States)

    Varga, G; DenBesten, P; Rácz, R; Zsembery, Á

    2017-08-18

    Dental enamel, the hardest mammalian tissue, is produced by ameloblasts. Ameloblasts show many similarities to other transporting epithelia although their secretory product, the enamel matrix, is quite different. Ameloblasts direct the formation of hydroxyapatite crystals, which liberate large quantities of protons that then need to be buffered to allow mineralization to proceed. Buffering requires a tight pH regulation and secretion of bicarbonate by ameloblasts. Many investigations have used immunohistochemical and knockout studies to determine the effects of these genes on enamel formation, but up till recently very little functional data were available for mineral ion transport. To address this, we developed a novel 2D in vitro model using HAT-7 ameloblast cells. HAT-7 cells can be polarized and develop functional tight junctions. Furthermore, they are able to accumulate bicarbonate ions from the basolateral to the apical fluid spaces. We propose that in the future, the HAT-7 2D system along with similar cellular models will be useful to functionally model ion transport processes during amelogenesis. Additionally, we also suggest that similar approaches will allow a better understanding of the regulation of the cycling process in maturation-stage ameloblasts, and the pH sensory mechanisms, which are required to develop sound, healthy enamel. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  17. Successful operative rib fixation of traumatic flail chest in a patient with osteogenesis imperfecta.

    Science.gov (United States)

    Kulaylat, Afif N; Chesnut, Charles H; Santos, Ariel P; Armen, Scott B

    2014-09-01

    Increasing attention has been directed towards operative rib fixation of traumatic flail chest; reported benefits include more rapid weaning from the ventilator, decreased intensive care unit stays, decreased complications and improved functional results. The outcomes of this surgical intervention in patients with osteogenesis imperfecta, a rare condition characterized by low bone density and bone fragility, are unknown. This case demonstrates that, in the management of traumatic flail chest in a patient with osteogenesis imperfecta, surgical fixation can be successful and should be considered early. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  18. 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)

  19. 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.

  20. Radiology of Osteogenesis Imperfecta, Rickets and Other Bony Fragility States.

    Science.gov (United States)

    Calder, Alistair D

    2015-01-01

    This section gives an overview of radiological findings in bony fragility states, with a special focus on osteogenesis imperfecta (OI) and rickets. Conventional radiological assessment of bone density is inaccurate and imprecise and only reliably detects severe osteopaenia. However, other aspects of bone structure and morphology can be assessed, and it is possible to distinguish between osteopaenic and osteomalacic states. OI is a heterogeneous group of disorders of type 1 collagen formation and processing that are characterised by varying degrees of bony fragility, with presentations varying from perinatal lethality to asymptomatic. Radiological diagnosis of severe forms is usually straightforward, but that of milder disease may be challenging because specific features are often absent. However, a multidisciplinary approach is usually successful. Features of OI, including Wormian bones, skull base deformities, vertebral involvement and long bone fractures and deformities, are reviewed in this section. Rickets is best defined as a disorder of the growth plate characterised by the impaired apoptosis of hypertrophied chondrocytes. Vitamin D deficiency is a common cause of rickets. The patho-anatomical basis of radiological findings in rickets is reviewed and illustrated. Rickets is frequently accompanied by hyperparathyroidism and osteomalacia. Rickets used to be classified as calciopaenic or phosphopaenic but is now referred to as parathyroid hormone or fibroblast growth factor 23 mediated, respectively [1]. The radiological features of the two forms are reviewed. © 2015 S. Karger AG, Basel.

  1. 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.

  2. [Vertebral fractures in children with Type I Osteogenesis imperfecta].

    Science.gov (United States)

    Sepúlveda, Andrea M; Terrazas, Claudia V; Sáez, Josefina; Reyes, María L

    2017-06-01

    Osteogenesis imperfecta (OI) is an hereditary disease affecting conective tissue, mainly associated to growth retardation and pathological fractures. OI type I (OI type I), is the mildest, most often, and homogeneous in its fenotype. Vertebral fractures are the most significant complications, associated to skeletical and cardiopulmonary morbidity. To characterize clinically a cohort of children with OI type I. A cohort of OI type I children younger than 20 year old was evaluated. Demographic, clinical, biochemical and radiological data were registered. Sixty seven patients were included, 55% male, 69% resident in the Metropolitan Region. The mean age of diagnose was 2.9 years, 70% presented vertebral fractures on follow-up, mostly thoracic, and 50% before the age of 5 years. Fifty percentage presented vertebral fractures at diagnose, which was about the age of 5 years. Bone metabolic parameters were in the normal range, without significant change at the moment of vertebral fractures. Calcium intake was found to be below American Academy of Pediatrics recommendations at the time of the first fracture. In this study OI type I has an early diagnose, and vertebral fractures show a high incidence, mostly in toddlers. Calcium intake was found to be below reccomended values, and should be closely supervised in these patients.

  3. 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

  4. 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

  5. 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.

  6. Osteogenesis imperfecta: rehabilitation approach with infants and young children.

    Science.gov (United States)

    Binder, H; Hawks, L; Graybill, G; Gerber, N L; Weintrob, J C

    1984-09-01

    A rehabilitation approach, consisting of initial handling and positioning followed by functional and formal strengthening exercises, was developed for the child with severe progressive osteogenesis imperfecta (OI). The program was developed because of the increased life expectancy for infants and children with severe progressive OI, combined with the lack of published reports dealing with their rehabilitation. The program can be followed easily by parents or therapists with regular monitoring by a psychiatrist. The goals are to improve the life span as well as the quality of life of these children by preventing the following: (1) positional contractures and deformities, (2) muscle weakness and osteoporosis, and (3) malalignment of the lower extremity joints prohibiting weight-bearing. Implementation of the program requires full cooperation of the parents. The initial results in four children between the ages of 3 and 11 years are encouraging. The benefits of increased strength and mobility leading to more age-appropriate activities and behaviors outweigh the only observed negative result, that is trauma-related lower extremity fractures in children with milder disease, and therefore greater mobility and higher activity levels.

  7. Comparative expression of the four enamel matrix protein genes, amelogenin, ameloblastin, enamelin and amelotin during amelogenesis in the lizard Anolis carolinensis.

    Science.gov (United States)

    Gasse, Barbara; Sire, Jean-Yves

    2015-01-01

    In a recent study, we have demonstrated that amelotin (AMTN) gene structure and its expression during amelogenesis have changed during tetrapod evolution. Indeed, this gene is expressed throughout enamel matrix deposition and maturation in non-mammalian tetrapods, while in mammals its expression is restricted to the transition and maturation stages of amelogenesis. Previous studies of amelogenin (AMEL) gene expression in a lizard and a salamander have shown similar expression pattern to that in mammals, but to our knowledge there are no data regarding ameloblastin (AMBN) and enamelin (ENAM) expression in non-mammalian tetrapods. The present study aims to look at, and compare, the structure and expression of four enamel matrix protein genes, AMEL, AMBN, ENAM and AMTN during amelogenesis in the lizard Anolis carolinensis. We provide the full-length cDNA sequence of A. carolinensis AMEL and AMBN, and show for the first time the expression of ENAM and AMBN in a non-mammalian species. During amelogenesis in A. carolinensis, AMEL, AMBN and ENAM expression in ameloblasts is similar to that described in mammals. It is noteworthy that AMEL and AMBN expression is also found in odontoblasts. Our findings indicate that AMTN is the only enamel matrix protein gene that is differentially expressed in ameloblasts between mammals and sauropsids. Changes in AMTN structure and expression could be the key to explain the structural differences between mammalian and reptilian enamel, i.e. prismatic versus non-prismatic.

  8. 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.

  9. 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.

  10. 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

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

    International Nuclear Information System (INIS)

    Rami, Parag M.; Heatwole, Eric V.; Boorstein, Jeffrey M.; McGraw, Kevin J.

    2002-01-01

    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.)

  12. 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…

  13. 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.

  14. 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...

  15. 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

  16. Osteogenesis imperfecta - iconographic study of two cases and review of the literature

    International Nuclear Information System (INIS)

    Souza, Ricardo Pires de; Fernandes, Cintia; Hilario, Marcelo Cobra; Barros, Wagner Moraes; Soares, Aldemir Humberto

    1996-01-01

    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)

  17. 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...

  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. 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…

  20. 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.

  1. Osteogenesis imperfecta in childhood: effects of spondylodesis on functional ability, ambulation and perceived competence

    NARCIS (Netherlands)

    Tolboom, N.; Cats, E. A.; Helders, P. J. M.; Pruijs, J. E. H.; Engelbert, R. H. H.

    2004-01-01

    We studied the effects of spondylodesis on spinal curvature, functional outcome, level of ambulation and perceived competence in 11 children with osteogenesis imperfecta (OI). Mean age at surgical intervention was 13.1 years (SD 2.5 years) and follow-up amounted to 3.4 years (SD 2.3 years). Spinal

  2. 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

  3. 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.

  4. 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.

  5. The clinical application of single-sperm-based SNP haplotyping for PGD of osteogenesis imperfecta.

    Science.gov (United States)

    Chen, Linjun; Diao, Zhenyu; Xu, Zhipeng; Zhou, Jianjun; Yan, Guijun; Sun, Haixiang

    2018-05-15

    Osteogenesis imperfecta (OI) is a genetically heterogeneous disorder, presenting either autosomal dominant, autosomal recessive or X-linked inheritance patterns. The majority of OI cases are autosomal dominant and are caused by heterozygous mutations in either the COL1A1 or COL1A2 gene. In these dominant disorders, allele dropout (ADO) can lead to misdiagnosis in preimplantation genetic diagnosis (PGD). Polymorphic markers linked to the mutated genes have been used to establish haplotypes for identifying ADO and ensuring the accuracy of PGD. However, the haplotype of male patients cannot be determined without data from affected relatives. Here, we developed a method for single-sperm-based single-nucleotide polymorphism (SNP) haplotyping via next-generation sequencing (NGS) for the PGD of OI. After NGS, 10 informative polymorphic SNP markers located upstream and downstream of the COL1A1 gene and its pathogenic mutation site were linked to individual alleles in a single sperm from an affected male. After haplotyping, a normal blastocyst was transferred to the uterus for a subsequent frozen embryo transfer cycle. The accuracy of PGD was confirmed by amniocentesis at 19 weeks of gestation. A healthy infant weighing 4,250 g was born via vaginal delivery at the 40th week of gestation. Single-sperm-based SNP haplotyping can be applied for PGD of any monogenic disorders or de novo mutations in males in whom the haplotype of paternal mutations cannot be determined due to a lack of affected relatives. ADO: allele dropout; DI: dentinogenesis imperfect; ESHRE: European Society of Human Reproduction and Embryology; FET: frozen embryo transfer; gDNA: genomic DNA; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; MDA: multiple displacement amplification; NGS: next-generation sequencing; OI: osteogenesis imperfect; PBS: phosphate buffer saline; PCR: polymerase chain reaction; PGD: preimplantation genetic diagnosis; SNP: single-nucleotide polymorphism; STR

  6. 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.

  7. X-ray micro-analysis of the mineralization patterns in developing enamel in hamster tooth germs exposed to fluoride in vitro during the secretory phase of amelogenesis

    International Nuclear Information System (INIS)

    Lyaruu, D.M.; Blijleven, N.; Hoeben-Schornagel, K.; Bronckers, A.L.; Woeltgens, J.H.

    1989-01-01

    The developing enamel from three-day-old hamster first maxillary (M1) molar tooth germs exposed to fluoride (F-) in vitro was analyzed for its mineral content by means of the energy-dispersive x-ray microanalysis technique. The aim of this study was to obtain semi-quantitative data on the F(-)-induced hypermineralization patterns in the enamel and to confirm that the increase in electron density observed in micrographs of F(-)-treated enamel is indeed due to an increase in mineral content in the fluorotic enamel. The tooth germs were explanted during the early stages of secretory amelogenesis and initially cultured for 24 hr in the presence of 10 ppm F- in the culture medium. The germs were then cultured for another 24 hr without F-. In order to compare the ultrastructural results directly with the microprobe data, we used the same specimens for both investigations. The net calcium counts (measurement minus background counts) in the analyses were used as a measure of the mineral content in the enamel. The aprismatic pre-exposure enamel, deposited in vivo before the onset of culture, was the most hypermineralized region in the fluorotic enamel, i.e., it contained the highest amount of calcium measured. The degree of the F(-)-induced hypermineralization gradually decreased (but was not abolished) in the more mature regions of the enamel. The unmineralized enamel matrix secreted during the initial F- treatment in vitro mineralized during the subsequent culture without F-. The calcium content in this enamel layer was in the same order of magnitude as that recorded for the newly deposited enamel in control tooth germs cultured without F-

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

    International Nuclear Information System (INIS)

    Janus, G.J.M.; Engelbert, R.H.H.; Beek, E.; Gooskens, R.H.J.M.; Pruijs, J.E.H.

    2003-01-01

    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 signs of

  9. 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

  10. 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.

  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. 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.

  13. 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.

  14. 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.

  15. 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

  16. Enamel renal syndrome: A rare case report

    Directory of Open Access Journals (Sweden)

    S V Kala Vani

    2012-01-01

    Full Text Available Enamel renal syndrome is a very rare disorder associating amelogenesis imperfecta with nephrocalcinosis. It is known by various synonyms such as amelogenesis imperfecta nephrocalcinosis syndrome, MacGibbon syndrome, Lubinsky syndrome, and Lubinsky-MacGibbon syndrome. It is characterized by enamel agenesis and medullary nephrocalcinosis. This paper describes enamel renal syndrome in a female patient born in a consanguineous family.

  17. 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.

  18. 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

  19. Altered corneal biomechanical properties in children with osteogenesis imperfecta.

    Science.gov (United States)

    Lagrou, Lisa M; Gilbert, Jesse; Hannibal, Mark; Caird, Michelle S; Thomas, Inas; Moroi, Sayoko E; Bohnsack, Brenda L

    2018-04-07

    To evaluate biomechanical corneal properties in children with osteogenesis imperfecta (OI). A prospective, observational, case-control study was conducted on children 6-19 years of age diagnosed with OI. Patients with OI and healthy control subjects underwent complete ophthalmic examinations. Additional tests included Ocular Response Analyzer (ORA) and ultrasonic pachymetry. Primary outcomes were central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF). Intraocular pressure (IOP) was measured directly by either iCare or Goldmann applanation and indirectly by the ORA (Goldmann-correlated and corneal-compensated IOP). Statistically significant differences between OI and control groups were determined using independent samples t test. A total of 10 of 18 OI cases (mean age, 13 ± 4.37 years; 8 males) and 30 controls (mean age, 12.76 ± 2.62 years; 16 males) were able to complete the corneal biomechanics and pachymetry testing. Children with OI had decreased CH (8.5 ± 1.0 mm Hg vs 11.6 ± 1.2 mm Hg [P < 0.001]), CRF (9.0 ± 1.9 mm Hg vs 11.5 ± 1.5 [P < 0.001]) and CCT (449.8 ± 30.8 μm vs 568 ± 47.6 μm [P < 0.001]) compared to controls. The corneal-compensated IOP was significantly higher in OI cases (18.8 ± 3.1 mm Hg) than in controls (15.0 ± 1.6 mm Hg, P < 0.004), but there was no significant difference in Goldmann-correlated IOP (16.3 ± 4.2 mm Hg vs 15.8 ± 2.2 mm Hg). Collagen defects in OI alter corneal structure and biomechanics. Children with OI have decreased CH, CRF, and CCT, resulting in IOPs that are likely higher than measured by tonometry. These corneal alterations are present at a young age in OI. Affected individuals should be routinely screened for glaucoma and corneal pathologies. Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  20. U.S. Army Medical Department Journal, January-March 2006

    Science.gov (United States)

    2006-03-01

    Caries Detection z MAJ Jerry Carbone, DC, USA, et al Prosthodontic Rehabilitation of a Patient with Amelogenesis Imperfecta: 41 A Clinical Report LTC...Rehabilitation of a having) posterior restorations you’ll enjoy LTC Patient with Amelogenesis Inpecta: A Clinical Nicholas Coppola’s "A Policy...Prosthodontic Rehabilitation of a Patient with Amelogenesis Imperfecta: A Clinical Report LTC Minaxi I. Patel, DC, USA LTC David A. Mott, DC, USA COL

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

    Directory of Open Access Journals (Sweden)

    Eugênia R. Valadares

    2014-11-01

    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. Resumo: Objetivo: Revisão da literatura sobre novos genes relacionados à osteogênese imperfeita (OI e atualização da sua classificação. Fonte dos dados: Revisão nas bases de dados do PUBMED e OMIM com seleção de referências relevantes. Síntese dos

  2. Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation.

    Science.gov (United States)

    Blouin, Stéphane; Fratzl-Zelman, Nadja; Glorieux, Francis H; Roschger, Paul; Klaushofer, Klaus; Marini, Joan C; Rauch, Frank

    2017-09-01

    In contrast to "classical" forms of osteogenesis imperfecta (OI) types I to IV, caused by a mutation in COL1A1/A2, OI type V is due to a gain-of-function mutation in the IFITM5 gene, encoding the interferon-induced transmembrane protein 5, or bone-restricted interferon-inducible transmembrane (IFITM)-like protein (BRIL). Its phenotype distinctly differs from OI types I to IV by absence of blue sclerae and dentinogenesis imperfecta, by the occurrence of ossification disorders such as hyperplastic callus and forearm interosseous membrane ossification. Little is known about the impact of the mutation on bone tissue/material level in untreated and bisphosphonate-treated patients. Therefore, investigations of transiliac bone biopsy samples from a cohort of OI type V children (n = 15, 8.7 ± 4 years old) untreated at baseline and a subset (n = 8) after pamidronate treatment (2.6 years in average) were performed. Quantitative backscattered electron imaging (qBEI) was used to determine bone mineralization density distribution (BMDD) as well as osteocyte lacunar density. The BMDD of type V OI bone was distinctly shifted toward a higher degree of mineralization. The most frequently occurring calcium concentration (CaPeak) in cortical (Ct) and cancellous (Cn) bone was markedly increased (+11.5%, +10.4%, respectively, p < 0.0001) compared to healthy reference values. Treatment with pamidronate resulted in only a slight enhancement of mineralization. The osteocyte lacunar density derived from sectioned bone area was elevated in OI type V Ct and Cn bone (+171%, p < 0.0001; +183.3%, p < 0.01; respectively) versus controls. The high osteocyte density was associated with an overall immature primary bone structure ("mesh-like") as visualized by polarized light microscopy. In summary, the bone material from OI type V patients is hypermineralized, similar to other forms of OI. The elevated osteocyte lacunar density in connection with lack of regular bone

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

    International Nuclear Information System (INIS)

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

    1987-01-01

    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. (orig.)

  4. 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.

  5. 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.

  6. 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

  7. Dentinogenesis imperfecta: a case report of comprehensive treatment for a teenager.

    Science.gov (United States)

    Biethman, Rick; Capati, Laura Richards; Eldger, Nicole

    2014-01-01

    Improving a smile can change a person's self-image. This case report describes treatment for an adolescent boy with dentinogenesis imperfecta. Soon to begin high school, the 14-year-old patient was severely obese and disliked his stained teeth. A combination of surgical periodontal treatment, endodontic treatment, and veneers improved both his smile and self-perception-which may have played a role in achieving his weight loss goal of 125 lb at 12 months post-treatment.

  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.

    Directory of Open Access Journals (Sweden)

    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: 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.

  12. 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)

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

  15. 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.

  16. Cytoskeleton and nuclear lamina affection in recessive osteogenesis imperfecta: A functional proteomics perspective.

    Science.gov (United States)

    Gagliardi, Assunta; Besio, Roberta; Carnemolla, Chiara; Landi, Claudia; Armini, Alessandro; Aglan, Mona; Otaify, Ghada; Temtamy, Samia A; Forlino, Antonella; Bini, Luca; Bianchi, Laura

    2017-09-07

    Osteogenesis imperfecta (OI) is a collagen-related disorder associated to dominant, recessive or X-linked transmission, mainly caused by mutations in type I collagen genes or in genes involved in type I collagen metabolism. Among the recessive forms, OI types VII, VIII, and IX are due to mutations in CRTAP, P3H1, and PPIB genes, respectively. They code for the three components of the endoplasmic reticulum complex that catalyzes 3-hydroxylation of type I collagen α1Pro986. Under-hydroxylation of this residue leads to collagen structural abnormalities and results in moderate to lethal OI phenotype, despite the exact molecular mechanisms are still not completely clear. To shed light on these recessive forms, primary fibroblasts from OI patients with mutations in CRTAP (n=3), P3H1 (n=3), PPIB (n=1) genes and from controls (n=4) were investigated by a functional proteomic approach. Cytoskeleton and nucleoskeleton asset, protein fate, and metabolism were delineated as mainly affected. While western blot experiments confirmed altered expression of lamin A/C and cofilin-1, immunofluorescence analysis using antibody against lamin A/C and phalloidin showed an aberrant organization of nucleus and cytoskeleton. This is the first report describing an altered organization of intracellular structural proteins in recessive OI and pointing them as possible novel target for OI treatment. OI is a prototype for skeletal dysplasias. It is a highly heterogeneous collagen-related disorder with dominant, recessive and X-linked transmission. There is no definitive cure for this disease, thus a better understanding of the molecular basis of its pathophysiology is expected to contribute in identifying potential targets to develop new treatments. Based on this concept, we performed a functional proteomic study to delineate affected molecular pathways in primary fibroblasts from recessive OI patients, carrying mutations in CRTAP (OI type VII), P3H1 (OI type VIII), and PPIB (OI type IX) genes

  17. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Short-term intravenous zoledronic acid in severe osteogenesis imperfecta : A report of three siblings of children

    Directory of Open Access Journals (Sweden)

    Hadyanto Lim

    2008-06-01

    Full Text Available This report documented the clinical and biochemical side effects on the first dose of intravenous zoledronic acid therapy in three siblings with severe osteogenesis imperfecta. Zoledronic acid was administered in 50 ml 0.9% saline solution over a period of 30 minutes. All patients had fever during the first 6 to 48 hours after the first infusion. There were no renal side effects, apart from asymptomatic hypocalcemia and hypophosphatemia at 48 and 72 hours after zoledronic acid infusion. The minimal clinical side effects were easily manageable. (Med J Indones 2008; 17: 127-30Keywords: zoledronic acid, osteogenesis imperfecta, side effects

  20. Severely impaired bone material quality in Chihuahua zebrafish resembles classical dominant human osteogenesis imperfecta.

    Science.gov (United States)

    Fiedler, Imke A K; Schmidt, Felix N; Wölfel, Eva M; Plumeyer, Christine; Milovanovic, Petar; Gioia, Roberta; Tonelli, Francesca; Bale, Hrishikesh A; Jähn, Katharina; Besio, Roberta; Forlino, Antonella; Busse, Björn

    2018-04-17

    Excessive skeletal deformations and brittle fractures in the vast majority of patients suffering from osteogenesis imperfecta (OI) are a result of substantially reduced bone quality. Since the mechanical competence of bone is dependent on the tissue characteristics at small length scales, it is of crucial importance to assess how osteogenesis imperfecta manifests at the micro- and nanoscale of bone. In this context, the Chihuahua (Chi/ +) zebrafish, carrying a heterozygous glycine substitution in the α1 chain of collagen type I, has recently been proposed as suitable animal model of classical dominant OI, showing skeletal deformities, altered mineralization patterns and a smaller body size. This study assessed the bone quality properties of Chi/+ at multiple length scales using micro-computed tomography (micro-CT), histomorphometry, quantitative back-scattered electron imaging, Fourier transform infrared spectroscopy, nanoindentation and X-ray microscopy. At the skeletal level, Chi/+ display smaller body size, deformities and fracture calli in the ribs. Morphological changes at the whole bone level showed that the vertebrae in Chi/+ had a smaller size, smaller thickness and distorted shape. At the tissue level, Chi/+ displayed a higher degree of mineralization, lower collagen maturity, lower mineral maturity, altered osteoblast morphology, and lower osteocyte lacunar density compared to WT. The alterations in the cellular, compositional and structural properties of Chi/+ bones bear an explanation for the impaired local mechanical properties, which promote an increase in overall bone fragility in Chi/ +. The quantitative assessment of bone quality in Chi/+ thus further validates this mutant as an important model reflecting osseous characteristics associated with human classical dominant osteogenesis imperfecta. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Osteogenesis imperfecta and hearing loss--description of three case reports.

    Science.gov (United States)

    Pereira da Silva, Ana; Feliciano, Telma; Figueirinhas, Rosário; Almeida E Sousa, Cecília

    2013-01-01

    Osteogenesis imperfecta is the commonest connective tissue hereditary disease. Its clinical presentation has a wide spectrum of characteristics, which includes skeletal deformities and hearing loss. We describe three case reports of individuals carriers of this disease presenting with different patterns of hearing loss. Hearing loss prevalence and patterns are variable and have no clear relation with genotype. Its assessment at initial evaluation and posterior monitoring is essential to provide the best therapeutic alternatives. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  6. Ultrastructural and immunocytochemical characterization of ameloblast-enamel adhesion at maturation stage in amelogenesis in Macaca fuscata tooth germ.

    Science.gov (United States)

    Sawada, Takashi

    2015-12-01

    Maturation-stage ameloblasts are firmly bound to the tooth enamel by a basal lamina-like structure. The mechanism underlying this adhesion, however, remains to be fully clarified. The goal of this study was to investigate the mechanism underlying adhesion between the basal lamina-like structure and the enamel in monkey tooth germ. High-resolution immunogold labeling was performed to localize amelotin and laminin 332 at the interface between ameloblasts and tooth enamel. Minute, electron-dense strands were observed on the enamel side of the lamina densa, extending into the degrading enamel matrix to produce a well-developed fibrous layer (lamina fibroreticularis). In un-demineralized tissue sections, mineral crystals smaller than those in the bulk of the enamel were observed adhering to these strands where they protruded into the surface enamel. Immunogold particles reactive for amelotin were preferentially localized on these strands in the fibrous layer. On the other hand, those for laminin 332 were localized solely in the lamina densa; none were observed in the fibrous layer. These results suggest that the fibrous layer of the basal lamina-like structure is partly composed of amelotin molecules, and that these molecules facilitate ameloblast-enamel adhesion by promoting mineralization of the fibrous layer during the maturation stage of amelogenesis.

  7. Scoliosis in children with osteogenesis imperfecta: influence of severity of disease and age of reaching motor milestones

    NARCIS (Netherlands)

    Engelbert, Raoul H. H.; Uiterwaal, Cuno S. P. M.; van der Hulst, Annelies; Witjes, Baukje; Helders, Paul J. M.; Pruijs, Hans E. H.

    2003-01-01

    We studied the relationship between the age of reaching motor milestones, especially anti-gravity activities, and the age of development of pathological spinal curvatures in children with osteogenesis imperfecta (OI). We hypothesized that earlier achievement of anti-gravity motor milestones predicts

  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. Fracture Rates and Fracture Sites in Patients With Osteogenesis Imperfecta: A Nationwide Register-Based Cohort Study

    DEFF Research Database (Denmark)

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

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  11. 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…

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

    International Nuclear Information System (INIS)

    Vieira, R.L.V.; Amaral, D.T.; Jesus-Garcia, Filho R.; Saraiva, G.; Fernandes, A.R.C.; Resnick, D.

    2006-01-01

    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.)

  13. 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.

  14. Intravenous pamidronate treatment in children with moderate-to-severe osteogenesis imperfecta started under three years of age

    NARCIS (Netherlands)

    Alcausin, M.B.; Briody, J.; Pacey, V.; Ault, J.; McQuade, M.; Bridge, C.; Engelbert, R.H.H.; Sillence, D.O.; Munns, C.F.

    OBJECTIVE: Evaluate clinical outcome of early cyclic intravenous pamidronate treatment in children with moderate-to-severe osteogenesis imperfecta (OI), commenced before three years of age. METHODS: A retrospective review of 17 patients with moderate-to-severe OI. Development, anthropometry,

  15. 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.

  16. Mutational analysis of COL1A1 and COL1A2 genes among Estonian osteogenesis imperfecta patients.

    Science.gov (United States)

    Zhytnik, Lidiia; Maasalu, Katre; Reimann, Ene; Prans, Ele; Kõks, Sulev; Märtson, Aare

    2017-08-15

    Osteogenesis imperfecta (OI) is a rare bone disorder. In 90% of cases, OI is caused by mutations in the COL1A1/2 genes, which code procollagen α1 and α2 chains. The main aim of the current research was to identify the mutational spectrum of COL1A1/2 genes in Estonian patients. The small population size of Estonia provides a unique chance to explore the collagen I mutational profile of 100% of OI families in the country. We performed mutational analysis of peripheral blood gDNA of 30 unrelated Estonian OI patients using Sanger sequencing of COL1A1 and COL1A2 genes, including all intron-exon junctions and 5'UTR and 3'UTR regions, to identify causative OI mutations. We identified COL1A1/2 mutations in 86.67% of patients (26/30). 76.92% of discovered mutations were located in the COL1A1 (n = 20) and 23.08% in the COL1A2 (n = 6) gene. Half of the COL1A1/2 mutations appeared to be novel. The percentage of quantitative COL1A1/2 mutations was 69.23%. Glycine substitution with serine was the most prevalent among missense mutations. All qualitative mutations were situated in the chain domain of pro-α1/2 chains. Our study shows that among the Estonian OI population, the range of collagen I mutations is quite high, which agrees with other described OI cohorts of Northern Europe. The Estonian OI cohort differs due to the high number of quantitative variants and simple missense variants, which are mostly Gly to Ser substitutions and do not extend the chain domain of COL1A1/2 products.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Mutational characterization of the P3H1/CRTAP/CypB complex in recessive osteogenesis imperfecta.

    Science.gov (United States)

    Barbirato, C; Trancozo, M; Almeida, M G; Almeida, L S; Santos, T O; Duarte, J C G; Rebouças, M R G O; Sipolatti, V; Nunes, V R R; Paula, F

    2015-12-03

    Osteogenesis imperfecta (OI) is a genetic disease characterized by bone deformities and fractures. Most cases are caused by autosomal dominant mutations in the type I collagen genes COL1A1 and COL1A2; however, an increasing number of recessive mutations in other genes have been reported. The LEPRE1, CRTAP, and PPIB genes encode proteins that form the P3H1/CRTAP/CypB complex, which is responsible for posttranslational modifications of type I collagen. In general, mutations in these genes lead to severe and lethal phenotypes of recessive OI. Here, we describe sixteen genetic variations detected in LEPRE1, CRTAP, and PPIB from 25 Brazilian patients with OI. Samples were screened for mutations on single-strand conformation polymorphism gels and variants were determined by automated sequencing. Seven variants were detected in patients but were absent in control samples. LEPRE1 contained the highest number of variants, including the previously described West African allele (c.1080+1G>T) found in one patient with severe OI as well as a previously undescribed p.Trp675Leu change that is predicted to be disease causing. In CRTAP, one patient carried the c.558A>G homozygous mutation, predicted as disease causing through alteration of a splice site. Genetic variations detected in the PPIB gene are probably not pathogenic due to their localization or because of their synonymous effect. This study enhances our knowledge about the mutational pattern of the LEPRE1, CRTAP, and PPIB genes. In addition, the results strengthen the proposition that LEPRE1 should be the first gene analyzed in mutation detection studies in patients with recessive OI.

  19. 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.

  20. 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.

  1. 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.

  2. Combined treatment with laser sintering and zirconium: a case report of dentinogenesis imperfecta.

    Science.gov (United States)

    Ayyildiz, Simel; Sahin, Cem; Akgün, Ozlem Marti; Basak, Feridun

    2013-01-01

    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.

  3. 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.)

  4. Osteogenesis Imperfecta Diagnosed from Mandibular and Lower Limb Fractures: A Case Report.

    Science.gov (United States)

    Kobayashi, Yoshikazu; Satoh, Koji; Mizutani, Hideki

    2016-06-01

    Osteogenesis imperfecta (OI) is a congenital disease characterized by bone fragility and low bone mass. Despite the variety of its manifestation and severity, facial fractures occur very infrequently. Here, we report a case of an infant diagnosed with OI after mandibular and lower limb fractures. A boy aged 1 year and 3 months was brought to his neighboring hospital with a complaint of facial injury. He was transferred to our hospital to undergo operation 3 days later. Computed tomography images revealed multiple mandibular fractures including complete fracture in the symphysis and dislocated condylar fracture on the right side. Open reduction and internal fixation with absorbable implants was performed 7 days after injury. He fractured his right lower limb 2 months later. He was diagnosed with OI type IA by an orthopedist. He will be administered bone-modifying agents if he suffers from frequent fractures.

  5. 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.

  6. 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.

  7. Clinical application of quantitative computed tomography in osteogenesis imperfecta-suspected cat.

    Science.gov (United States)

    Won, Sungjun; Chung, Woo-Jo; Yoon, Junghee

    2017-09-30

    One-year-old male Persian cat presented with multiple fractures and no known traumatic history. Marked decrease of bone radiopacity and thin cortices of all long bones were identified on radiography. Tentative diagnosis was osteogenesis imperfecta, a congenital disorder characterized by fragile bone. To determine bone mineral density (BMD), quantitative computed tomography (QCT) was performed. The QCT results revealed a mean trabecular BMD of vertebral bodies of 149.9 ± 86.5 mg/cm 3 . After bisphosphonate therapy, BMD of the same site increased significantly (218.5 ± 117.1 mg/cm 3 , p < 0.05). QCT was a useful diagnostic tool to diagnose osteopenia and quantify response to medical treatment.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Splenomegaly, myeloid lineage expansion and increased osteoclastogenesis in osteogenesis imperfecta murine.

    Science.gov (United States)

    Matthews, Brya G; Roeder, Emilie; Wang, Xi; Aguila, Hector Leonardo; Lee, Sun-Kyeong; Grcevic, Danka; Kalajzic, Ivo

    2017-10-01

    Osteogenesis imperfecta (OI) is a disease caused by defects in type I collagen production that results in brittle bones. While the pathology is mainly caused by defects in the osteoblast lineage, there is also elevated bone resorption by osteoclasts resulting in high bone turnover in severe forms of the disease. Osteoclasts originate from hematopoietic myeloid cells, however changes in hematopoiesis have not been previously documented in OI. In this study, we evaluated hematopoietic lineage distribution and osteoclast progenitor cell frequency in bone marrow, spleen and peripheral blood of osteogenesis imperfecta murine (OIM) mice, a model of severe OI. We found splenomegaly in all ages examined, and expansion of myeloid lineage cells (CD11b + ) in bone marrow and spleen of 7-9week old male OIM animals. OIM spleens also showed an increased frequency of purified osteoclast progenitors. This phenotype is suggestive of chronic inflammation. Isolated osteoclast precursors from both spleen and bone marrow formed osteoclasts more rapidly than wild-type controls. We found that serum TNFα levels were increased in OIM, as was IL1α in OIM females. We targeted inflammation therapeutically by treating growing animals with murine TNFR2:Fc, a compound that blocks TNFα activity. Anti-TNFα treatment marginally decreased spleen mass in OIM females, but failed to reduce bone resorption, or improve bone parameters or fracture rate in OIM animals. We have demonstrated that OIM mice have changes in their hematopoietic system, and form osteoclasts more rapidly even in the absence of OI osteoblast signals, however therapy targeting TNFα did not improve disease parameters. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. 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

  14. Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Oestreich, Arin K; Kamp, William M; McCray, Marcus G; Carleton, Stephanie M; Karasseva, Natalia; Lenz, Kristin L; Jeong, Youngjae; Daghlas, Salah A; Yao, Xiaomei; Wang, Yong; Pfeiffer, Ferris M; Ellersieck, Mark R; Schulz, Laura C; Phillips, Charlotte L

    2016-11-22

    During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstn tm1Sjl/+ ) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstn tm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2 oim ), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2 oim/+ offspring from natural mating of Mstn tm1Sjl/+ dams to Col1a2 oim/+ sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2 oim/+ dams to Col1a2 oim/+ sires. Finally, increased bone biomechanical strength of Col1a2 oim/+ offspring that had been transferred into Mstn tm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta.

  15. 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

  16. 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.

  17. Novel compound heterozygous mutations in SERPINH1 cause rare autosomal recessive osteogenesis imperfecta type X.

    Science.gov (United States)

    Song, Y; Zhao, D; Xu, X; Lv, F; Li, L; Jiang, Y; Wang, O; Xia, W; Xing, X; Li, M

    2018-03-09

    We identified novel compound heterozygous mutations in SERPINH1 in a Chinese boy suffering from recurrent fractures, femoral deformities, and growth retardation, which resulted in extremely rare autosomal recessive OI type X. Long-term treatment of BPs was effective in increasing BMD Z-score, reducing fracture incidence and reshaping vertebrae compression. Osteogenesis imperfecta (OI) is a heritable bone disorder characterized by low bone mineral density, recurrent fractures, and progressive bone deformities. Mutation in serpin peptidase inhibitor clade H, member 1 (SERPINH1), which encodes heat shock protein 47 (HSP47), leads to rare autosomal recessive OI type X. We aimed to detect the phenotype and the pathogenic mutation of OI type X in a boy from a non-consanguineous Chinese family. We investigated the pathogenic mutations and analyzed their relationship with the phenotype in the patient using next-generation sequencing (NGS) and Sanger sequencing. Moreover, the efficacy of long-term bisphosphonate treatment in this patient was evaluated. The patient suffered from multiple fractures, low bone mass, and bone deformities in the femur, without dentinogenesis imperfecta or hearing loss. Compound heterozygous variants were found in SERPINH1 as follows: c.149 T>G in exon 2 and c.1214G>A in exon 5. His parents were heterozygous carriers of each of these mutations, respectively. Bisphosphonates could be helpful in increasing BMD Z-score, reducing bone fracture risk and reshaping the compressed vertebral bodies of this patient. We reported novel compound heterozygous mutations in SERPINH1 in a Chinese OI patient for the first time, which expanded the spectrum of phenotype and genotype of extremely rare OI type X.

  18. 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

  19. 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.

  20. 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...

  1. 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

  2. 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

  3. Osteogenesis Imperfecta

    Science.gov (United States)

    ... cure, but you can manage symptoms. Treatments include exercise, pain medicine, physical therapy, wheelchairs, braces, and surgery. NIH: National Institute of Arthritis and Musculoskeletal and Skin Diseases

  4. Osteogenesis imperfecta type 3 in South Africa: Causative mutations in FKBP10

    Directory of Open Access Journals (Sweden)

    Alvera Vorster

    2017-05-01

    Full Text Available Background. A relatively high frequency of autosomal recessively inherited osteogenesis imperfecta (OI type 3 (OI-3 is present in the indigenous black southern African population. Affected persons may be severely handicapped as a result of frequent fractures, progressive deformity of the tubular bones and spinal malalignment. Objective. To delineate the molecular basis for the condition. Methods. Molecular investigations were performed on 91 affected persons from seven diverse ethnolinguistic groups in this population. Results. Following polymerase chain reaction amplification and direct cycle sequencing, FKBP10 mutations were identified in 45.1% (41/91 OI-3-affected persons. The homozygous FKBP10 c.831dupC frameshift mutation was confirmed in 35 affected individuals in the study cohort. Haplotype analysis suggests that this mutation is identical among these OI-3-affected persons by descent, thereby confirming that they had a common ancestor. Compound heterozygosity of this founder mutation was observed, in combination with three different deleterious FKBP10 mutations, in six additional persons in the cohort. Four of these individuals had the c.831delC mutation. Conclusion. The burden of the disorder, both in frequency and severity, warrants the establishment of a dedicated service for molecular diagnostic confirmation and genetic management of persons and families with OI in southern Africa.

  5. 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.)

  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. Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice.

    Science.gov (United States)

    Vanleene, Maximilien; Porter, Alexandra; Guillot, Pascale-Valerie; Boyde, Alan; Oyen, Michelle; Shefelbine, Sandra

    2012-06-01

    Bone is a complex material with a hierarchical multi-scale organization from the molecule to the organ scale. The genetic bone disease, osteogenesis imperfecta, is primarily caused by mutations in the collagen type I genes, resulting in bone fragility. Because the basis of the disease is molecular with ramifications at the whole bone level, it provides a platform for investigating the relationship between structure, composition, and mechanics throughout the hierarchy. Prior studies have individually shown that OI leads to: 1. increased bone mineralization, 2. decreased elastic modulus, and 3. smaller apatite crystal size. However, these have not been studied together and the mechanism for how mineral structure influences tissue mechanics has not been identified. This lack of understanding inhibits the development of more accurate models and therapies. To address this research gap, we used a mouse model of the disease (oim) to measure these outcomes together in order to propose an underlying mechanism for the changes in properties. Our main finding was that despite increased mineralization, oim bones have lower stiffness that may result from the poorly organized mineral matrix with significantly smaller, highly packed and disoriented apatite crystals. Using a composite framework, we interpret the lower oim bone matrix elasticity observed as the result of a change in the aspect ratio of apatite crystals and a disruption of the crystal connectivity. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. 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.

  9. Standardized X-ray reports of the spine in osteogenesis imperfecta

    International Nuclear Information System (INIS)

    Koerber, Friederike; Demant, A.W.; Koerber, S.; Semler, O.; Schoenau, E.; Lackner, K.J.

    2011-01-01

    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.)

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Rehabilitation of children and infants with osteogenesis imperfecta. A program for ambulation.

    Science.gov (United States)

    Gerber, L H; Binder, H; Weintrob, J; Grange, D K; Shapiro, J; Fromherz, W; Berry, R; Conway, A; Nason, S; Marini, J

    1990-02-01

    Management of children and infants with osteogenesis imperfecta (OI) poses difficult decisions for pediatricians, orthopedists, and physiatrists. These children are frequently frail with disabling bone and joint deformities and fractures. In an eight-year cumulative management of 12 children with OI, a comprehensive program included strengthening exercises to the pelvic girdle and lower extremity muscles, in addition to pool exercises and molded seating to support upright posture. Long leg braces were fitted when the children were able to sit unsupported. All 12 were fitted with braces; nine were functional ambulators, and three were home ambulators. Six children required femoral plating or rodding, two of whom subsequently had the metal removed. Lower extremity fractures averaged one and one-half per year prior to bracing for nine children who had fractures. There was 0.83 fracture per year for the ten children who had fractures after bracing. The degree of femoral bowing increased in four, decreased in four, and remained unchanged in four, while the degree of tibial bowing increased in two, decreased in nine, and remained unchanged in one during the observation period. A comprehensive rehabilitation program and long leg bracing with surgical operations on the femur result in a high level of functional activity for children with OI with an acceptable level of risk for fracture.

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

    Science.gov (United States)

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

    2004-12-01

    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, electrocardiography, and echocardiography. Exercise capacity was measured using a maximal exercise test on a bicycle ergometer and an expired gas analysis system. Muscle strength in shoulder abductors, hip flexors, ankle dorsal flexor, and grip strength were measured. All results were compared with reference values. Cardiopulmonary function at rest was within normal ranges, but when it was compared with normal height for age and sex, vital capacities were reduced. Mean absolute and relative VO 2 peak were respectively -1.17 (+/- 0.67) and -1.41 (+/- 1.52) standard deviations lower compared with reference values ( P exercise tolerance and muscle strength were significantly reduced in patients with OI, which might account for their increased levels of fatigue during activities of daily living.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Pregnancy- and lactation-associated transient osteoporosis of both hips in a 32 year old patient with osteogenesis imperfecta.

    Science.gov (United States)

    Pabinger, C; Heu, C; Frohner, A; Dimai, H P

    2012-07-01

    Combination of osteogenesis imperfecta (OI), pregnancy, and transient osteoporosis (TO) of the hip is rare, only a few cases have been published so far. We report a 32 year old woman with OI, with TO on the right hip in her late third trimester. Non-pharmacological measures such as non-weight-bearing resulted in complete remission. Shortly after weaning, TO of the contralateral hip developed and non-pharmacological measures remained ineffective this time. Under treatment with a prostaglandin I(2) analog (iloprost), i.v. bisphosphonate (pamidronate), calcium and vitamin D supplementation rapid improvement of pain and complete remission was achieved. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. 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.

  8. 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...

  9. 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.

  10. Skeletal phenotypes in adult patients with osteogenesis imperfecta-correlations with COL1A1/COL1A2 genotype and collagen structure

    DEFF Research Database (Denmark)

    Hald, J D; 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...

  11. Bone geometry, density, and microarchitecture in the distal radius and tibia in adults with osteogenesis imperfecta type I assessed by high-resolution 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 type I collagen that leads to decreased bone mass and increased bone fragility. We hypothesized that patients with OI have altered bone microstructure and bone geometry...

  12. Specific entities affecting the craniocervical region: osteogenesis imperfecta and related osteochondrodysplasias: medical and surgical management of basilar impression.

    Science.gov (United States)

    Menezes, Arnold H

    2008-10-01

    Osteogenesis imperfecta (OI) is an inheritable disorder of bone development caused by defective collagen synthesis. The attendant basilar impression or secondary basilar invagination is uncommon but can be devastating. Fifty-two patients with osteochondrodysplasia (28 with OI, six with Hajdu-Cheney syndrome, six with Paget's disease, and 12 with spondyloepiphyseal dysplasia) with basilar impression were evaluated between 1985 and 2005. The male/female ratio in this cohort was 1:1. The mean age at presentation was 12.2 years. Symptoms and signs included headache, lower cranial nerve dysfunction, dysphagia, respiratory embarrassment, weakness, and ataxia. In the earlier part of the series (1985-1995), all patients with hydrocephalus were shunted and a ventral transoral decompression made for ventral compression of the pontomedullary junction followed by a dorsal occipitocervical fusion. As a result of this evaluation, it was felt that most patients would benefit by early bracing after the hydrocephalus was shunted if it existed. However, 20% of patients still required an anterior ventral decompression and the occipitocervical fusion. The results showed that the fusions were stable but over a period of time, there was progressive forward bending with osteogenesis imperfecta as well as with the Hajdu-Cheney syndrome. All patients with spondyloepiphyseal dysplasia had a good strong stable fusion which stood the test of time. In conclusion, we feel that early intervention with occipitocervical bracing can prevent the progressive march of significant basilar impression which leads to mortality.

  13. Fluoroscopy-guided Sacroiliac Joint Steroid Injection for Low Back Pain in a Patient with Osteogenesis Imperfecta.

    Science.gov (United States)

    Dawson, P U; Rose, R E; Wade, N A

    2015-09-01

    Osteogenesis imperfecta, also known as 'brittle bone disease', is a genetic connective tissue disease. It is characterized by bone fragility and osteopenia (low bone density). In this case, a 57-year old female presented to the University Hospital of the West Indies (UHWI), Physical Medicine and Rehabilitation Clinic with left low back pain rated 6/10 on the numeric rating scale (NRS). Clinically, the patient had sacroiliac joint mediated pain although X-rays did not show the sacroiliac joint changes. Fluoroscopy-guided left sacroiliac joint steroid injection was done. Numeric rating scale and Oswestry Disability Index (ODI) questionnaire were used to evaluate outcome. This was completed at baseline, one week follow-up and at eight weeks post fluoroscopy-guided sacroiliac joint steroid injection. Numeric rating scale improved from 6/10 before the procedure to 0/10 post procedure, and ODI questionnaire score improved from a moderate disability score of 40% to a minimal disability score of 13%. Up to eight weeks, the NRS was 0/10 and ODI remained at minimal disability of 15%. Fluoroscopy-guided sacroiliac joint injection is a known diagnostic and treatment method for sacroiliac joint mediated pain. To our knowledge, this is the first case published on the use of fluoroscopy-guided sacroiliac joint steroid injection in the treatment of sacroiliac joint mediated low back pain in a patient with osteogenesis imperfecta.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Macroscopic anisotropic bone material properties in children with severe osteogenesis imperfecta.

    Science.gov (United States)

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

    2017-11-07

    Children with severe osteogenesis imperfecta (OI) typically experience numerous fractures and progressive skeletal deformities over their lifetime. Recent studies proposed finite element models to assess fracture risk and guide clinicians in determining appropriate intervention in children with OI, but lack of appropriate material property inputs remains a challenge. This study aimed to characterize macroscopic anisotropic cortical bone material properties and investigate relationships with bone density measures in children with severe OI. Specimens were obtained from tibial or femoral shafts of nine children with severe OI and five controls. The specimens were cut into beams, characterized in bending, and imaged by synchrotron radiation X-ray micro-computed tomography. Longitudinal modulus of elasticity, yield strength, and bending strength were 32-65% lower in the OI group (p<0.001). Yield strain did not differ between groups (p≥0.197). In both groups, modulus and strength were lower in the transverse direction (p≤0.009), but anisotropy was less pronounced in the OI group. Intracortical vascular porosity was almost six times higher in the OI group (p<0.001), but no differences were observed in osteocyte lacunar porosity between the groups (p=0.086). Volumetric bone mineral density was lower in the OI group (p<0.001), but volumetric tissue mineral density was not (p=0.770). Longitudinal OI bone modulus and strength were correlated with volumetric bone mineral density (p≤0.024) but not volumetric tissue mineral density (p≥0.099). Results indicate that cortical bone in children with severe OI yields at the same strain as normal bone, and that their decreased bone material strength is associated with reduced volumetric bone mineral density. These results will enable the advancement of fracture risk assessment capability in children with severe OI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Occlusal features and need for orthodontic treatment in persons with osteogenesis imperfecta

    Science.gov (United States)

    Binh, Ho Duy; Nguyen, Khac Minh; Maasalu, Katre; Kõks, Sulev; Märtson, Aare; Saag, Mare; Jagomägi, Triin

    2017-01-01

    Abstract The aim of the study was to (a) analyse dental occlusion and determine the need for orthodontic treatment of persons with osteogenesis imperfecta (OI) in comparison with the healthy population and (b) investigate the associations between OI and malocclusion. A case‐control study included 26 OI persons and 400 healthy participants (control group). Occlusal features and the need for orthodontic treatment were defined according to Dental Health Component‐Index of Orthodontic Treatment Need and Dental Aesthetic Index. Results showed that Angle Class I, II, and III relationship was found in 23.1%, 3.8%, and 73.1% of OI group, and in the control group, it was 67%, 17.5%, and 15.5%, respectively. OI group had significantly higher prevalence of reverse overjet >1 mm (76.9%), missing teeth (42.3%), posterior crossbite (34.6%), and open bite >2 mm (19.2%) compared to the control group (8.5%, 2.2%, 6.2%, and 3.5%, respectively). OI group had less incisal segment crowding and more incisal segment spacing than the control group (p  1 mm (OR = 13.3, 95% CI = 3.9–44.7, p < .001), Angle Class III malocclusion (OR = 8.0, 95% CI = 2.0–30.8, p = .003), and missing teeth (OR = 4.7, 95% CI = 1.0–22.4, p = .049). In conclusion, there is the high probability of malocclusion in OI persons. Persons with OI require early orthodontic treatment because of significant correlation of OI disease with Angle Class III malocclusion, reverse overjet, and missing teeth. PMID:29744175

  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. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Deficiency of CRTAP in non-lethal recessive osteogenesis imperfecta reduces collagen deposition into matrix.

    Science.gov (United States)

    Valli, M; Barnes, A M; Gallanti, A; Cabral, W A; Viglio, S; Weis, M A; Makareeva, E; Eyre, D; Leikin, S; Antoniazzi, F; Marini, J C; Mottes, M

    2012-11-01

    Deficiency of any component of the ER-resident collagen prolyl 3-hydroxylation complex causes recessive osteogenesis imperfecta (OI). The complex modifies the α1(I)Pro986 residue and contains cartilage-associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1) and cyclophilin B (CyPB). Fibroblasts normally secrete about 10% of CRTAP. Most CRTAP mutations cause a null allele and lethal type VII OI. We identified a 7-year-old Egyptian boy with non-lethal type VII OI and investigated the effects of his null CRTAP mutation on collagen biochemistry, the prolyl 3-hydroxylation complex, and collagen in extracellular matrix. The proband is homozygous for an insertion/deletion in CRTAP (c.118_133del16insTACCC). His dermal fibroblasts synthesize fully overmodified type I collagen, and 3-hydroxylate only 5% of α1(I)Pro986. CRTAP transcripts are 10% of control. CRTAP protein is absent from proband cells, with residual P3H1 and normal CyPB levels. Dermal collagen fibril diameters are significantly increased. By immunofluorescence of long-term cultures, we identified a severe deficiency (10-15% of control) of collagen deposited in extracellular matrix, with disorganization of the minimal fibrillar network. Quantitative pulse-chase experiments corroborate deficiency of matrix deposition, rather than increased matrix turnover. We conclude that defects of extracellular matrix, as well as intracellular defects in collagen modification, contribute to the pathology of type VII OI. © 2011 John Wiley & Sons A/S.

  10. 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.

  11. Intrafibrillar Mineral May be Absent in Dentinogenesis Imperfecta Type II (DI-II); TOPICAL

    International Nuclear Information System (INIS)

    Pople, John A.

    2001-01-01

    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

  12. EPIDEMIOLOGÍA DE LA OSTEOGÉNESIS IMPERFECTA: UNA ENFERMEDAD RARA EN LA COMUNITAT VALENCIANA

    Directory of Open Access Journals (Sweden)

    Silvia Gimeno-Marto

    2017-01-01

    Full Text Available Fundamentos: La Osteogénesis Imperfecta (OI es una enfermedad rara del tejido conectivo y óseo que resulta en una fragilidad ósea de diversa severidad. El objetivo fue determinar y describir la situación de la OI en la Comunitat Valenciana (CV durante el periodo 2004-2014. Métodos: A partir del Sistema de Información de Enfermedades Raras de la CV (SIER-CV se identificaron los pacientes con los códigos de la Cla - sificación Internacional de Enfermedades pertenecientes a la OI: el 756.51 de la 9ª y/o el Q78.0 de la 10ª revisión, durante el período 2004-2014. Se va - lidaron los datos mediante la revisión de documentación clínica (historia clí - nica electrónica principalmente y de los casos confirmados (diagnóstico de OI presente en la documentación clínica se elaboró un análisis descriptivo. Resultados: Se identificaron 162 pacientes con código de OI. Se con - firmaron 145 casos de los 161 con la documentación clínica accesible. La prevalencia fue de 0,29 por 10.000 habitantes. El 93,1% eran españoles, el 54,5% mujeres y fueron atendidos en 25 hospitales diferentes de la CV. Se identificó el tipo de OI en el 24,8% de los casos, siendo el tipo I el más habitual (9,7%. Fallecieron el 6,2% con una edad media al fallecimiento de 60,8 años. El 44,8% de pacientes recibió tratamiento con bifosfonatos y el 10,4% tenían familiares afectados. Conclusión: Se ha establecido la situación real de la OI en la CV, lo que permitirá una mejor planificación en las acciones sanitarias para mejorar la calidad de vida de los afectados y sus familiares.

  13. Splicing defect in FKBP10 gene causes autosomal recessive osteogenesis imperfecta disease: a case report.

    Science.gov (United States)

    Maghami, Fatemeh; Tabei, Seyed Mohammad Bagher; Moravej, Hossein; Dastsooz, Hassan; Modarresi, Farzaneh; Silawi, Mohammad; Faghihi, Mohammad Ali

    2018-05-25

    Osteogenesis imperfecta (OI) is a group of connective tissue disorder caused by mutations of genes involved in the production of collagen and its supporting proteins. Although the majority of reported OI variants are in COL1A1 and COL1A2 genes, recent reports have shown problems in other non-collagenous genes involved in the post translational modifications, folding and transport, transcription and proliferation of osteoblasts, bone mineralization, and cell signaling. Up to now, 17 types of OI have been reported in which types I to IV are the most frequent cases with autosomal dominant pattern of inheritance. Here we report an 8- year- old boy with OI who has had multiple fractures since birth and now he is wheelchair-dependent. To identify genetic cause of OI in our patient, whole exome sequencing (WES) was carried out and it revealed a novel deleterious homozygote splice acceptor site mutation (c.1257-2A > G, IVS7-2A > G) in FKBP10 gene in the patient. Then, the identified mutation was confirmed using Sanger sequencing in the proband as homozygous and in his parents as heterozygous, indicating its autosomal recessive pattern of inheritance. In addition, we performed RT-PCR on RNA transcripts originated from skin fibroblast of the proband to analyze the functional effect of the mutation on splicing pattern of FKBP10 gene and it showed skipping of the exon 8 of this gene. Moreover, Real-Time PCR was carried out to quantify the expression level of FKBP10 in the proband and his family members in which it revealed nearly the full decrease in the level of FKBP10 expression in the proband and around 75% decrease in its level in the carriers of the mutation, strongly suggesting the pathogenicity of the mutation. Our study identified, for the first time, a private pathogenic splice site mutation in FKBP10 gene and further prove the involvement of this gene in the rare cases of autosomal recessive OI type XI with distinguished clinical manifestations.

  14. Assessment of quality of life of parents of children with osteogenesis imperfecta.

    Science.gov (United States)

    Szczepaniak-Kubat, Anna; Kurnatowska, Olga; Jakubowska-Pietkiewicz, Elzbieta; Chlebna-Sokół, Danuta

    2012-01-01

    The aim of the work was an objective assessment of the quality of life of parents of children with osteogenesis imperfecta (OI) and of its determinant factors. The survey answers of 25 parents were analyzed and contained demographic parameters, socioeconomic status information, quality of life of responses and type of support they have been receiving. In order to assess the effects of this children's disease on the quality of life of the parents, families were divided into two groups depending on the OI severity: group M--mild (type I and IV OI), group S--severe (type III OI). The objective of the work was carried out based on the WHOQOL-BREF quality of life questionnaire and measures of family status: education degree based on the International Standard Classification of Education (ISCED), a subjective assessment of the family's wealth (Perceived Family Wealth, PFW), and the family's financial resources (Family Affluence Scale, FAS). 56% of respondents assessed their global quality of life (Quality of Life, QL) as good, whereas 8% answered poor. Perception of general health status was similar. Life domains assessed in the WHOQOL-BREF questionnaire received the following mean values on a scale from 4 to 20 points: physical--12.2 +/- 1.2, psychological--15.04 +/- 2.2, environmental--13.32 +/- 2, social relationships--14.28 +/- 1.5. In the severe OI group, the environmental domain was assessed as worse than in the mild OI group and this assessment was statistically significant, despite the fact that the group of families with severe cases of OI received more support from the appropriate institutions. Indicators of socioeconomic status did not affect the respondents' assessment of their global quality of life. In the tested group of families, the child's disease did not affect either the global quality of life assessment or health of the respondents or their quality of life in terms of physical and mental status and social relationships. The parents of children with

  15. 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

  16. 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

  17. 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

  18. Hyperplastic callus formation in osteogenesis imperfecta type V: follow-up of three generations over ten years

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  19. 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.

  20. 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.)

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Molecular Basis of Human Enamel Defects

    Directory of Open Access Journals (Sweden)

    Chatzopoulos Georgios

    2014-03-01

    Full Text Available During eruption of teeth in the oral cavity, the effect of gene variations and environmental factors can result in morphological and structural changes in teeth. Amelogenesis imperfecta is a failure which is detected on the enamel of the teeth and clinical picture varies by the severity and type of the disease. Classification of the types of amelogenesis imperfecta is determined by histological, genetic, clinical and radiographic criteria. Specifically, there are 4 types of amelogenesis imperfecta (according to Witkop: hypoplastic form, hypo-maturation form, hypo-calcified form, and hypo-maturation/hypoplasia form with taurodontism and 14 subcategories. The diagnosis and classification of amelogenesis imperfecta has traditionally been based on clinical presentation or phenotype and the inheritance pattern. Several genes can be mutated and cause the disease. Millions of genes, possibly more than 10,000 genes produce proteins that regulate synthesis of enamel. Some of the genes and gene products that are likely associated with amelogenesis imperfecta are: amelogenin (AMELX, AMELY genes, ameloblastin (AMBN gene, enamelin (ENAM gene, enamelysin (MMP20 gene, kalikryn 4 (KLK 4 gene, tuftelins (Tuftelin gene, FAM83H (FAM83H gene and WDR72 (WDR72 gene. Particular attention should be given by the dentist in recognition and correlation of phenotypes with genotypes, in order to diagnose quickly and accurately such a possible disease and to prevent or treat it easily and quickly. Modern dentistry should restore these lesions in order to guarantee aesthetics and functionality, usually in collaboration with a group of dentists.

  8. Adaptor protein complex 2-mediated, clathrin-dependent endocytosis, and related gene activities, are a prominent feature during maturation stage amelogenesis.

    Science.gov (United States)

    Lacruz, Rodrigo S; Brookes, Steven J; Wen, Xin; Jimenez, Jaime M; Vikman, Susanna; Hu, Ping; White, Shane N; Lyngstadaas, S Petter; Okamoto, Curtis T; Smith, Charles E; Paine, Michael L

    2013-03-01

    Molecular events defining enamel matrix removal during amelogenesis are poorly understood. Early reports have suggested that adaptor proteins (AP) participate in ameloblast-mediated endocytosis. Enamel formation involves the secretory and maturation stages, with an increase in resorptive function during the latter. Here, using real-time PCR, we show that the expression of clathrin and adaptor protein subunits are upregulated in maturation stage rodent enamel organ cells. AP complex 2 (AP-2) is the most upregulated of the four distinct adaptor protein complexes. Immunolocalization confirms the presence of AP-2 and clathrin in ameloblasts, with strongest reactivity at the apical pole. These data suggest that the resorptive functions of enamel cells involve AP-2 mediated, clathrin-dependent endocytosis, thus implying the likelihood of specific membrane-bound receptor(s) of enamel matrix protein debris. The mRNA expression of other endocytosis-related gene products is also upregulated during maturation including: lysosomal-associated membrane protein 1 (Lamp1); cluster of differentiation 63 and 68 (Cd63 and Cd68); ATPase, H(+) transporting, lysosomal V0 subunit D2 (Atp6v0d2); ATPase, H(+) transporting, lysosomal V1 subunit B2 (Atp6v1b2); chloride channel, voltage-sensitive 7 (Clcn7); and cathepsin K (Ctsk). Immunohistologic data confirms the expression of a number of these proteins in maturation stage ameloblasts. The enamel of Cd63-null mice was also examined. Despite increased mRNA and protein expression in the enamel organ during maturation, the enamel of Cd63-null mice appeared normal. This may suggest inherent functional redundancies between Cd63 and related gene products, such as Lamp1 and Cd68. Ameloblast-like LS8 cells treated with the enamel matrix protein complex Emdogain showed upregulation of AP-2 and clathrin subunits, further supporting the existence of a membrane-bound receptor-regulated pathway for the endocytosis of enamel matrix proteins. These data

  9. Adaptor Protein Complex 2 (AP-2) Mediated, Clathrin Dependent Endocytosis, And Related Gene Activities, Are A Prominent Feature During Maturation Stage Amelogenesis

    Science.gov (United States)

    LACRUZ, Rodrigo S.; BROOKES, Steven J.; WEN, Xin; JIMENEZ, Jaime M.; VIKMAN, Susanna; HU, Ping; WHITE, Shane N.; LYNGSTADAAS, S. Petter; OKAMOTO, Curtis T.; SMITH, Charles E.; PAINE, Michael L.

    2012-01-01

    Molecular events defining enamel matrix removal during amelogenesis are poorly understood. Early reports have suggested that adaptor proteins (AP) participate in ameloblast-mediated endocytosis. Enamel formation involves the secretory and maturation stages, with an increase in resorptive function during the latter. Here, using real time PCR, we show that the expression of clathrin and adaptor protein subunits are up-regulated in maturation stage rodent enamel organ cells. AP-2 is the most up-regulated of the four distinct adaptor protein complexes. Immunolocalization confirms the presence of AP-2 and clathrin in ameloblasts with strongest reactivity at the apical pole. These data suggest that the resorptive functions of enamel cells involve AP-2 mediated, clathrin dependent endocytosis, thus implying the likelihood of a specific membrane-bound receptor(s) of enamel matrix protein debris. The mRNA expression of other endocytosis-related gene products is also up-regulated during maturation including: lysosomal-associated membrane protein 1 (Lamp1), cluster of differentiation 63 and 68 (Cd63 and Cd68), ATPase, H+ transporting, lysosomal V0 subunit D2 (Atp6v0d2), ATPase, H+ transporting, lysosomal V1 subunit B2 (Atp6v1b2), chloride channel, voltage-sensitive 7 (Clcn7) and cathepsin K (Ctsk). Immunohistological data confirms the expression of a number of these proteins in maturation stage ameloblasts. The enamel of Cd63-null mice was also examined. Despite increased mRNA and protein expression in the enamel organ during maturation, the enamel of Cd63-null mice appeared normal. This may suggest inherent functional redundancies between Cd63 and related gene products, such as Lamp1 and Cd68. Ameloblast-like LS8 cells treated with the enamel matrix protein complex Emdogain® showed up-regulation of AP-2 and clathrin subunits, further supporting the existence of a membrane-bound receptor regulated pathway for the endocytosis of enamel matrix proteins. These data together

  10. 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.

  11. 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.

  12. Mortality and Causes of Death in Patients With Osteogenesis Imperfecta: A Register-Based Nationwide Cohort Study

    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...... five to one to the OI cohort. We calculated hazard ratios for all-cause mortality and subhazard ratios for cause-specific mortality in a comparison of the OI cohort and the reference population. We also calculated all-cause mortality hazard ratios for males, females, and age groups (0 to 17.99 years......, 18.00 to 34.99 years, 35.00 to 54.99 years, 55.00 to 74.99 years, and >75 years). We identified 687 cases of OI (379 women) and included 3435 reference persons (1895 women). A total of 112 patients with OI and 257 persons in the reference population died during the observation period. The all-cause...

  13. Anesthetic management of an 8-month-old infant with osteogenesis imperfecta undergoing liver transplantation: a case report.

    Science.gov (United States)

    Lee, Jiwon; Ryu, Ho-Geol; Kim, Anna; Yoo, Seokha; Shin, Seung-Yeon; Kang, Sun-Hye; Jeong, Jinyoung; Yoo, Yongjae

    2014-06-01

    Anesthetic management of pediatric liver transplantation in a patient with osteogenesis imperfecta (OI) requires tough decisions and comprehensive considerations of the cascade of effects that may arise and the required monitoring. Total intravenous anesthesia (TIVA) with propofol and remifentanil was chosen as the main anesthetic strategy. Malignant hyperthermia (MH), skeletal fragility, anhepatic phase during liver transplantation, uncertainties of TIVA in children, and propofol infusion syndrome were considered and monitored. There were no adverse events during the operation. Despite meticulous precautions with regard to the risk of MH, there was an episode of high fever (40℃) in the ICU a few hours after the operation, which was initially feared as MH. Fortunately, MH was ruled out as the fever subsided soon after hydration and antipyretics were given. Although the delivery of supportive care and the administration of dantrolene are the core principles in the management of MH, perioperative fever does not always mean a MH in patients at risk for MH, and other common causes of fever should also be considered.

  14. Multi-scale analysis of bone chemistry, morphology and mechanics in the oim model of osteogenesis imperfecta.

    Science.gov (United States)

    Bart, Zachary R; Hammond, Max A; Wallace, Joseph M

    2014-08-01

    Osteogenesis imperfecta is a congenital disease commonly characterized by brittle bones and caused by mutations in the genes encoding Type I collagen, the single most abundant protein produced by the body. The oim model has a natural collagen mutation, converting its heterotrimeric structure (two α1 and one α2 chains) into α1 homotrimers. This mutation in collagen may impact formation of the mineral, creating a brittle bone phenotype in animals. Femurs from male wild type (WT) and homozygous (oim/oim) mice, all at 12 weeks of age, were assessed using assays at multiple length scales with minimal sample processing to ensure a near-physiological state. Atomic force microscopy (AFM) demonstrated detectable differences in the organization of collagen at the nanoscale that may partially contribute to alterations in material and structural behavior obtained through mechanical testing and reference point indentation (RPI). Changes in geometric and chemical structure obtained from µ-Computed Tomography and Raman spectroscopy indicate a smaller bone with reduced trabecular architecture and altered chemical composition. Decreased tissue material properties in oim/oim mice are likely driven by changes in collagen fibril structure, decreasing space available for mineral nucleation and growth, as supported by a reduction in mineral crystallinity. Multi-scale analyses of this nature offer much in assessing how molecular changes compound to create a degraded, brittle bone phenotype.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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