WorldWideScience

Sample records for achondroplasia

  1. Achondroplasia

    Science.gov (United States)

    ... growth that causes the most common type of dwarfism. Causes Achondroplasia is one of a group of ... the condition. Symptoms The typical appearance of achondroplastic dwarfism can be seen at birth. Symptoms may include: ...

  2. Genetics Home Reference: achondroplasia

    Science.gov (United States)

    ... Share: Email Facebook Twitter Home Health Conditions Achondroplasia Achondroplasia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Achondroplasia is a form of short-limbed dwarfism. The ...

  3. Achondroplasia and Macular Coloboma.

    Science.gov (United States)

    Ahoor, M H; Amizadeh, Y; Sorkhabi, R

    2015-01-01

    Achondroplasia is an autosomal dominant congenital disorder of enchondral ossification. It is clinically characterized by low stature, craniofacial deformity, and vertebral malformation. Associated ophthalmic features include telecanthus, exotropia, angle anomalies, and cone-rod dystrophy. A 24-year-old male presented with decreased vision bilaterally and typical achondroplasia. The best corrected visual acuity was 20/70 in both eyes. Anterior segment examination was normal. Fundus examination revealed a well-demarcated circular paramacular lesion in both eyes. As macular coloboma and achondroplasia are developmental disorders, the funduscopic examination is required in patients with achondroplasia.

  4. Neurologic manifestations of achondroplasia.

    Science.gov (United States)

    Hecht, Jacqueline T; Bodensteiner, John B; Butler, Ian J

    2014-01-01

    Achondroplasia is the best described and most common form of the congenital short-limbed dwarfing conditions. Achondroplasia is apparent at birth and has a birth prevalence of 1 in 20000-30000 live-born infants. Achondroplasia is inherited as an autosomal dominant condition, although 80% of cases occur sporadically as new events in their families. Achondroplasia is caused, in virtually all of the cases, by a G380R mutation in fibroblast growth factor receptor 3 (FGFR3). Patients with achondroplasia should be evaluated by a multidisciplinary team of clinicians including geneticists, neurologists, and orthopedists, since there are numerous bony and neurological complications. The most severe complication results from craniocervical stenosis and medullary and upper spinal cord compression, which can have devastating and even lethal sequelae during early childhood. In subsequent decades, including adolescence, spinal cord and nerve compression are more prominent. The neurological complications of achondroplasia have been recognized in adults for more than a century and are attributed to bony defects, connective tissue structures, or both. Similar neurological complications are now appreciated in infants, young children, and teenagers with achondroplasia. Defective connective tissue elements in achondroplasia frequently lead to ligamentous laxity, which can aggravate the complications associated with bony stenosis. Bony abnormalities are known to cause neurological morbidity and lead to a shortened lifespan. Neurological complications associated with achondroplasia are reviewed, including recommendations for the evaluation and management of these clinical problems. © 2014 Elsevier B.V. All rights reserved.

  5. Achondroplasia: Really rhizomelic?

    Science.gov (United States)

    Shelmerdine, Susan Cheng; Brittain, Helen; Arthurs, Owen J; Calder, Alistair D

    2016-08-01

    Achondroplasia is the most common form of short limb dwarfism in humans. The shortening of the limb lengths in achondroplasia is widely described as "rhizomelic." While this appearance may be convincing clinically, the description is not necessarily true or helpful radiologically. The aims of this study, were therefore, to determine whether rhizomelic shortening is a true feature of achondroplasia at diagnosis in infancy. Humeral, radial, femoral, and tibial diaphyseal lengths were recorded by two independent observers from 22 skeletal surveys of infants with achondroplasia and compared with 150 normal age-matched control subjects. Upper and lower limb bone length ratios (radial/humeral and tibial/femoral lengths, respectively) in both groups were compared using an unpaired t-test. Mean upper limb length ratios were statistically higher within the achondroplasia group at 0.87 ± 0.04 (n = 22, mean age 70 ± 94 days) compared to normal controls at 0.79 ± 0.02 (n = 150, mean age 113 days ± 88 days; P achondroplasia demonstrate statistically significant rhizomelic shortening within the upper limbs, but not lower limbs at diagnosis, compared to normal controls. The term "rhizomelic shortening" in relation to achondroplasia should be reserved when describing upper limb proportions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Clinical management of achondroplasia.

    Science.gov (United States)

    Wright, M J; Irving, M D

    2012-02-01

    Achondroplasia, one of the skeletal dysplasias and the commonest form of disproportionate short stature, has a different developmental and growth profile compared to average stature children. In addition, a specific group of complications occur more frequently in children with achondroplasia. These include common but usually relatively minor complications such as recurrent otitis media, and rarer but more severe problems such as cervicomedullary compression. Knowledge of these complications, appropriate surveillance strategies and treatment options is essential for the paediatrician. The authors review the published literature in this area and provide a system based approach to the management of the healthcare needs of the child with achondroplasia.

  7. Growth Modulation in Achondroplasia.

    Science.gov (United States)

    McClure, Philip K; Kilinc, Eray; Birch, John G

    2017-09-01

    Achondroplasia is the most common skeletal dysplasia with a rate of nearly 1/10,000. The development of lower extremity deformity is well documented, and various modes of correction have been reported. There are no reports on the use of growth modulation to correct angular deformity in achondroplasia. Medical Records from 1985 to 2015 were reviewed for the diagnosis of achondroplasia and growth modulation procedures. Patients who had been treated for angular deformity of the legs by growth modulation were identified. A detailed analysis of their medical record and preoperative and final lower extremity radiographs was completed. Four patients underwent growth modulation procedures, all to correct existing varus deformity of the legs. Three of the 4 patients underwent bilateral distal femoral and proximal tibial growth modulation. The remaining patient underwent tibial correction only. Two of the 4 patients had a combined proximal fibular epiphysiodesis. All limbs had some improvement of alignment; however, 1 patient went on to bilateral osteotomies. Only 1 limb corrected to a neutral axis with growth modulation alone at last follow-up, initial implantation was done before 5 years of age. Growth modulation is an effective means for deformity correction in the setting of achondroplasia. However implantation may need to be done earlier than would be typical for patients without achondroplasia. Osteotomy may still be required after growth modulation for incomplete correction.

  8. Molecular studies of achondroplasia

    Directory of Open Access Journals (Sweden)

    Nahar Risha

    2009-01-01

    Full Text Available Background: Achondroplasia (ACH is the most frequent form of short-limbed dwarfi sm, caused by mutations in the FGFR3 gene. It follows an autosomal dominant inheritance, though most cases are sporadic. The molecular techniques are the only available methods to confi rm the diagnosis of a skeletal dysplasia. Clinical and radiological features are only suggestive and not confi rmatory. The present study was conducted to fi nd out how often the clinical diagnosis of achondroplasia is verifi ed on molecular studies. Materials and Methods: From 1998 through 2007, we carried out molecular analysis for the two common mutations in the FGFR3 gene in 130 cases clinically suspected to have ACH. Results: A diagnostic mutation was identifi ed in 53 (40.8% cases. The common mutation (1138G>A was present in 50 (94.7% of the positive cases, while the rare 1138 G>C substitution was found in three (5.3%. Conclusion: This study shows that confi rmation of clinical diagnosis of ACH by molecular genetic testing is essential to distinguish it from other skeletal dysplasias, to plan therapeutic options, and to offer genetic counseling. Management (medical and surgical in patients confi rmed to have ACH, is briefl y discussed.

  9. Achondroplasia Associated with Bilateral Keratoconus

    Directory of Open Access Journals (Sweden)

    Ammar M. Al Mahmood

    2012-01-01

    Full Text Available We report a rare case of bilateral keratoconus in association with achondroplasia. A 26-year-old male, with a known case of achondroplasia, complained of bilateral gradual deterioration in vision for the past few years. Slit lamp biomicroscopy showed bilateral central corneal protrusion and stromal thinning at the apex consistent with keratoconus. a trial of hard contact lens fitting failed to improve VA in the left eye (LE. Right eye (RE improved to 20/25. The patient underwent penetrating keratoplasty (PKP in his LE. Twenty-seven months postoperatively, uncorrected visual acuity (UCVA was 20/30. Ophthalmologists should be aware that patients with achondroplasia who complain of poor vision should be suspected of having keratoconus once other more common conditions are ruled out.

  10. Discoid Meniscus Associated With Achondroplasia.

    Science.gov (United States)

    Hoernschemeyer, Daniel G; Atanda, Alfred; Dean-Davis, Ellen; Gupta, Sumit K

    2016-05-01

    Achondroplasia is the most common skeletal dysplasia. This form of dwarfism is caused by a point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, leading to inhibition of endochondral ossification for these patients. This results in a normal trunk height but shortened limbs. The discoid meniscus may be an important associated finding to better understand the common complaints of leg pain for these patients. Although the incidence for a discoid meniscus is between 3% and 5% for the general population, it is unknown with achondroplasia. This case series includes 4 patients, with ages ranging from adolescence to early adulthood, with symptoms of knee pain that were not attributable to some of the more common findings seen in this patient population. Typically, patients with achondroplasia who experience knee pain are evaluated for more common and well-known etiologies such as genu varum, ligamentous instability, and neurogenic claudication. However, the authors propose that symptomatic discoid lateral meniscus should be added to the differential diagnosis for lower-extremity pain in the achondroplasia population. A thorough history and physical examination, in combination with magnetic resonance imaging, can aid in making the diagnosis. Treatment with arthroscopic debridement, saucerization of the meniscus, and repair for unstable injuries has yielded good outcomes for this patient population. [Orthopedics. 2016; 39(3):e498-e503.]. Copyright 2016, SLACK Incorporated.

  11. Achondroplasia and multiple-suture craniosynostosis.

    Science.gov (United States)

    Albino, Frank P; Wood, Benjamin C; Oluigbo, Chima O; Lee, Angela C; Oh, Albert K; Rogers, Gary F

    2015-01-01

    Genetic mutations in the fibroblast growth factor receptor 3 gene may lead to achondroplasia or syndromic forms of craniosynostosis. Despite sharing a common genetic basis, craniosynostosis has rarely been described in cases of confirmed achondroplasia. We report an infant with achondroplasia who developed progressive multiple-suture craniosynostosis to discuss the genetic link between these clinical entities and to describe the technical challenges associated with the operative management.

  12. Karakteristik Dan perawatan Anomali Ortodonsia Pada Beberapa Penderita Achondroplasia

    OpenAIRE

    Agustina, Nova

    2010-01-01

    Karakteristik dan Perawatan Anomali Ortodonsia pada Beberapa Penderita Achondroplasia xii + 56 halaman Kelainan genetik dapat berpengaruh terhadap gangguan dentofasial. Achondroplasia adalah salah satu kelainan genetik yang mempunyai manifestasi timbulnya gangguan dentofasial. Achondroplasia adalah salah satu bentuk dwarfisme yang sering dijumpai. Achondroplasia disebabkan oleh gangguan osifikasi endokondral akibat mutasi gen FGFR 3 (fibroblast growth factor receptor 3) pada lengan p...

  13. Achondroplasia in sibs of normal parents.

    Science.gov (United States)

    Philip, N; Auger, M; Mattei, J F; Giraud, F

    1988-01-01

    A new case of recurrent achondroplasia in sibs of normal parents is reported. Two sisters and a half sister were affected. Various mechanisms can be postulated to account for unexpected recurrence of achondroplasia in the same sibship. Germinal mosaicism and unstable premutation are discussed here. Images PMID:3236371

  14. Achondroplasia in sibs of normal parents.

    OpenAIRE

    Philip, N; Auger, M; Mattei, J F; Giraud, F

    1988-01-01

    A new case of recurrent achondroplasia in sibs of normal parents is reported. Two sisters and a half sister were affected. Various mechanisms can be postulated to account for unexpected recurrence of achondroplasia in the same sibship. Germinal mosaicism and unstable premutation are discussed here.

  15. Intracranial MR imaging of achondroplasia

    International Nuclear Information System (INIS)

    Ueno, Shinichi; Ootsuka, Ryouichi; Hayashi, Yoshinori; Nishitani, Hiromu; Shirakawa, Norihisa; Hashimoto, Toshiaki

    1992-01-01

    Intracranial MR imaging was performed in five patients with achondroplasia. All patients had narrowing of the subarachnoid space at the level of the formen magnum that was mainly due to protrusion of the posterior aspect. Three patients had compressive deformities of the brainstem and/or upper cervical spine. Among them, two patients had deformities of the pons. Relative upward displacement of the brainstem was seen in all patients. Hydrocephalus was seen in three patients. (author)

  16. Intracranial MR imaging of achondroplasia

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Shinichi; Ootsuka, Ryouichi; Hayashi, Yoshinori; Nishitani, Hiromu; Shirakawa, Norihisa; Hashimoto, Toshiaki (Tokushima Univ. (Japan). School of Medicine)

    1992-10-01

    Intracranial MR imaging was performed in five patients with achondroplasia. All patients had narrowing of the subarachnoid space at the level of the formen magnum that was mainly due to protrusion of the posterior aspect. Three patients had compressive deformities of the brainstem and/or upper cervical spine. Among them, two patients had deformities of the pons. Relative upward displacement of the brainstem was seen in all patients. Hydrocephalus was seen in three patients. (author).

  17. Achondroplasia and enchondromatosis: report of three boys

    Energy Technology Data Exchange (ETDEWEB)

    Numakura, Chikahiko [Yamagata University School of Medicine, Department of Pediatrics, Yamagata (Japan); Tokyo Metropolitan Kiyose Children' s Hospital, Endocrinology and Metabolism Unit, Tokyo (Japan); Kobayashi, Hironori [Shimane University School of Medicine, Department of Pediatrics, Shimane (Japan); Hasegawa, Yukihiro [Tokyo Metropolitan Kiyose Children' s Hospital, Endocrinology and Metabolism Unit, Tokyo (Japan); Adachi, Masanori [Kanagawa Children' s Medical Center, Department of Endocrinology and Metabolism, Clinical Research Institute, Kanagawa (Japan); Kim, Ok Hwa [Ajou University Hospital, Department of Radiology, Seoul (Korea); Nishimura, Gen [Tokyo Metropolitan Kiyose Children' s Hospital, Department of Radiology, Tokyo (Japan)

    2007-06-15

    We report on three boys suffering from achondroplasia concurrent with enchondromatosis-like metaphyseal changes. Two boys who were examined by molecular analysis harbored a mutation of FGFR3, which occurs in most achondroplastic individuals. Given the prevalence of achondroplasia and enchondromatosis, the metaphyseal changes in these patients are less likely to represent the coincidence of both disorders, but rather to result from a rare consequence of the FGFR3 mutation. Impaired FGFs/FGFR3 signaling pathway in achondroplasia inhibits chondrocytic proliferation, which accounts for most characteristics of achondroplasia. On the other hand, it causes conflicting biological consequences that can suppress or stimulate chondrocytic maturation. In a small subset of achondroplastic individuals, the suppression of chondrocytic maturation may outweigh the stimulation, which leads to cartilaginous overgrowth into the metaphysis, eventually causing the metaphyseal dysplasia found in the present patients. (orig.)

  18. Anaesthetic Challenges Associated with Achondroplasia: A Case ...

    African Journals Online (AJOL)

    IFEOMA

    KEYWORDS: Emergency cesarean section, achondroplasia, difficult airway, subarachnoid block, General ... thesia, with delivery of a live female child. Details of the .... in the lateral position. ... ture during epidurals, inability to advance the.

  19. Achondroplasia and enchondromatosis: report of three boys

    International Nuclear Information System (INIS)

    Numakura, Chikahiko; Kobayashi, Hironori; Hasegawa, Yukihiro; Adachi, Masanori; Kim, Ok Hwa; Nishimura, Gen

    2007-01-01

    We report on three boys suffering from achondroplasia concurrent with enchondromatosis-like metaphyseal changes. Two boys who were examined by molecular analysis harbored a mutation of FGFR3, which occurs in most achondroplastic individuals. Given the prevalence of achondroplasia and enchondromatosis, the metaphyseal changes in these patients are less likely to represent the coincidence of both disorders, but rather to result from a rare consequence of the FGFR3 mutation. Impaired FGFs/FGFR3 signaling pathway in achondroplasia inhibits chondrocytic proliferation, which accounts for most characteristics of achondroplasia. On the other hand, it causes conflicting biological consequences that can suppress or stimulate chondrocytic maturation. In a small subset of achondroplastic individuals, the suppression of chondrocytic maturation may outweigh the stimulation, which leads to cartilaginous overgrowth into the metaphysis, eventually causing the metaphyseal dysplasia found in the present patients. (orig.)

  20. Achondroplasia: Development, pathogenesis, and therapy.

    Science.gov (United States)

    Ornitz, David M; Legeai-Mallet, Laurence

    2017-04-01

    Autosomal dominant mutations in fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include hypochondroplasia (Hch), severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia (TD). FGFR3 is expressed in chondrocytes and mature osteoblasts where it functions to regulate bone growth. Analysis of the mutations in FGFR3 revealed increased signaling through a combination of mechanisms that include stabilization of the receptor, enhanced dimerization, and enhanced tyrosine kinase activity. Paradoxically, increased FGFR3 signaling profoundly suppresses proliferation and maturation of growth plate chondrocytes resulting in decreased growth plate size, reduced trabecular bone volume, and resulting decreased bone elongation. In this review, we discuss the molecular mechanisms that regulate growth plate chondrocytes, the pathogenesis of Ach, and therapeutic approaches that are being evaluated to improve endochondral bone growth in people with Ach and related conditions. Developmental Dynamics 246:291-309, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Respiratory difficulties and breathing disorders in achondroplasia.

    Science.gov (United States)

    Afsharpaiman, S; Saburi, A; Waters, Karen A

    2013-12-01

    Respiratory difficulties and breathing disorders in achondroplasia are thought to underlie the increased risk for sudden infant death and neuropsychological deficits seen in this condition. This review evaluates literature regarding respiratory dysfunctions and their sequelae in patients with achondroplasia. The limited number of prospective studies of respiratory disease in achondroplasia means that observational studies and case series provide a large proportion of the data regarding the spectrum of respiratory diseases in achondroplasia and their treatments. Amongst clinical respiratory problems described, snoring is the commonest observed abnormality, but the reported incidence of obstructive sleep apnoea (OSA) shows wide variance (10% to 75%). Reported treatments of OSA include adenotonsillectomy, the use of CPAP, and surgical improvement of the airway, including mid-face advancement. Otolaryngologic manifestations are also common. Respiratory failure due to small thoracic volumes is reported, but uncommon. Mortality rate at all ages was 2.27 (CI: 1.7-3.0) with age-specific mortality increased at all ages. Sudden death was most common in infants and children. Cardiovascular events are the main cause of mortality in adults. Despite earlier recognition and treatment of respiratory complications of achondroplasia, increased mortality rates and other complications remain high. Future and ongoing evaluation of the prevalence and impact of respiratory disorders, particularly OSA, in achondroplasia is recommended. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  2. Analysis of sagittal spinopelvic parameters in achondroplasia.

    Science.gov (United States)

    Hong, Jae-Young; Suh, Seung-Woo; Modi, Hitesh N; Park, Jong-Woong; Park, Jung-Ho

    2011-08-15

    Prospective radiological analysis of patients with achondroplasia. To analyze sagittal spinal alignment and pelvic orientation in achondroplasia patients. Knowledge of sagittal spinopelvic parameters is important for the treatment of achondroplasia, because they differ from those of the normal population and can induce pain. The study and control groups were composed of 32 achondroplasia patients and 24 healthy volunteers, respectively. All underwent lateral radiography of the whole spine including hip joints. The radiographic parameters examined were sacral slope (SS), pelvic tilt, pelvic incidence (PI), S1 overhang, thoracic kyphosis, T10-L2 kyphosis, lumbar lordosis (LL1, LL2), and sagittal balance. Statistical analysis was performed to identify significant differences between the two groups. In addition, correlations between parameters and symptoms were sought. Sagittal spinopelvic parameters, namely, pelvic tilt, pelvic incidence, S1 overhang, thoracic kyphosis, T10-L2 kyphosis, lumbar lordosis 1 and sagittal balance were found to be significantly different in the patient and control groups (P achondroplasia patients and normal healthy controls. The present study shows that sagittal spinal and pelvic parameters can assist the treatment of spinal disorders in achondroplasia patients.

  3. Manifestasi Penyakit Achondroplasia Di Rongga Mulut Ditinjau Dari Gambaran Radiografi

    OpenAIRE

    Tengku Ayu Masitah

    2009-01-01

    Achondroplasia merupakan penyakit pertumbuhan tulang yang genetik (turunan) dan biasanya terjadi satu dari setiap 20.000 kelahiran. Achondroplasia sebagian besar berasal dari tipe dwarfism (kekerdilan). Gambaran radiografi pada penderita Achondroplasia menunjukkan adanya pembesaran tengkorak, penyempitan foramen magnum, frontal bossing, penekanan nasal bridge, hipoplasia maksila, protrusi mandibula melebihi jarak normal, garis tengah muka hipoplasia, maloklusi, beberapa gigi permanen yang te...

  4. Achondroplasia: pathogenesis and implications for future treatment.

    Science.gov (United States)

    Laederich, Melanie B; Horton, William A

    2010-08-01

    Although the genetic defect underlying achondroplasia has been known for over a decade, no effective therapies to stimulate bone growth have emerged. Here we review the recent literature and summarize the molecular mechanisms underlying disease pathology and examine their potential as therapeutic targets. Currently used preclinical models are discussed in the context of recent advances with a special focus on C-type natriuretic peptide. Research on the mutation in Fibroblast Growth Factor Receptor 3 (FGFR3) that causes achondroplasia suggests that disease results from increased signal transduction from the mutant receptor. Thus, current therapeutic strategies have focused on reducing signals emanating from FGFR3. First-generation therapies directly targeting FGFR3, such as kinase inhibitors and neutralizing antibodies, designed for targeting FGFR3 in cancer, are still in the preclinical phase and have yet to translate into the management of achondroplasia. Counteracting signal transduction pathways downstream of FGFR3 holds promise with the discovery that administration of C-type natriuretic peptide to achondroplastic mice ameliorates their clinical phenotype. However, more research into long-term effectiveness and safety of this strategy is needed. Direct targeting of therapeutic agents to growth plate cartilage may enhance efficacy and minimize side effects of these and future therapies. Current research into the pathogenesis of achondroplasia has expanded our understanding of the mechanisms of FGFR3-induced disease and has increased the number of approaches that we may use to potentially correct it. Further research is needed to validate these approaches in preclinical models of achondroplasia.

  5. Optimal management of complications associated with achondroplasia

    Science.gov (United States)

    Ireland, Penny J; Pacey, Verity; Zankl, Andreas; Edwards, Priya; Johnston, Leanne M; Savarirayan, Ravi

    2014-01-01

    Achondroplasia is the most common form of skeletal dysplasia, resulting in disproportionate short stature, and affects over 250,000 people worldwide. Individuals with achondroplasia demonstrate a number of well-recognized anatomical features that impact on growth and development, with a complex array of medical issues that are best managed through a multidisciplinary team approach. The complexity of this presentation, whereby individual impairments may impact upon multiple activity and participation areas, requires consideration and discussion under a broad framework to gain a more thorough understanding of the experience of this condition for individuals with achondroplasia. This paper examines the general literature and research evidence on the medical and health aspects of individuals with achondroplasia and presents a pictorial model of achondroplasia based on The International Classification of Functioning, Disability, and Health (ICF). An expanded model of the ICF will be used to review and present the current literature pertaining to the musculoskeletal, neurological, cardiorespiratory, and ear, nose, and throat impairments and complications across the lifespan, with discussion on the impact of these impairments upon activity and participation performance. Further research is required to fully identify factors influencing participation and to help develop strategies to address these factors. PMID:25053890

  6. Achondroplasia

    Science.gov (United States)

    ... Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Careers Archives Health Topics Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...

  7. Optimal management of complications associated with achondroplasia

    Directory of Open Access Journals (Sweden)

    Irel

    2014-06-01

    Full Text Available Penny J Ireland,1 Verity Pacey,2,3 Andreas Zankl,4 Priya Edwards,1 Leanne M Johnston,5 Ravi Savarirayan6 1Queensland Paediatric Rehabilitation Service, Royal Children’s Hospital, Herston, Brisbane, Queensland, 2Physiotherapy Department, The Children’s Hospital at Westmead, Sydney, New South Wales, 3Department of Health Professions, Macquarie University, Sydney, New South Wales, 4Genetic Medicine, Children’s Hospital, Westmead, Sydney, New South Wales, 5School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, Queensland, 6Victorian Clinical Genetics Service, Royal Children’s Hospital, Melbourne, Victoria, Australia Abstract: Achondroplasia is the most common form of skeletal dysplasia, resulting in disproportionate short stature, and affects over 250,000 people worldwide. Individuals with achondroplasia demonstrate a number of well-recognized anatomical features that impact on growth and development, with a complex array of medical issues that are best managed through a multidisciplinary team approach. The complexity of this presentation, whereby individual impairments may impact upon multiple activity and participation areas, requires consideration and discussion under a broad framework to gain a more thorough understanding of the experience of this condition for individuals with achondroplasia. This paper examines the general literature and research evidence on the medical and health aspects of individuals with achondroplasia and presents a pictorial model of achondroplasia based on The International Classification of Functioning, Disability, and Health (ICF. An expanded model of the ICF will be used to review and present the current literature pertaining to the musculoskeletal, neurological, cardiorespiratory, and ear, nose, and throat impairments and complications across the lifespan, with discussion on the impact of these impairments upon activity and participation performance. Further research is required to

  8. A RARE CASE OF ACHONDROPLASIA- SHORT LIMB

    Directory of Open Access Journals (Sweden)

    B. Ravichander

    2017-03-01

    Full Text Available BACKGROUND A 6-year-old boy was presented to the paediatric department with shortening of all the limbs and delay in growth. Clinical examinations revealed height less than third percentile along with other abnormalities like frontal bossing, midfacial hypoplasia, flattened nasal bridge, short neck and rhizomelic type of shortening of all the limbs. These clinical features raised the diagnosis towards achondroplasia, which was further supported by radiologic evidence. Achondroplasia is a disorder involving growth of bone. The conversion of cartilage to bone is hampered. The affection is particularly seen in the long bones of arms and legs. The characterising features of this disorder are dwarfism, limitation in range of motion at the elbows, enlarged size of head, small fingers, but with normal intelligence. Other complications like apnoea, obesity, recurrent ear infections and lordosis of the spine are often associated with achondroplasia. The basic defect in achondroplasia lies in mutations of the FGFR3 gene. It is an autosomal dominant disorder.

  9. Airway malacia in children with achondroplasia.

    Science.gov (United States)

    Dessoffy, Kimberly E; Modaff, Peggy; Pauli, Richard M

    2014-02-01

    This study was undertaken to assess the frequency of airway malacia in infants and young children with achondroplasia, a population well known to be at risk for a variety of respiratory problems. We also wished to evaluate what, if any, contribution airway malacia makes to the complex respiratory issues that may be present in those with achondroplasia. Retrospective chart review of all infants and young children with achondroplasia who were assessed through the Midwest Regional Bone Dysplasia Clinics from 1985 through 2012 (n = 236) was completed. Records of comprehensive clinical examinations, polysomnographic assessments, and airway visualization were reviewed and abstracted using a data collection form. Analyses were completed comparing the group with and those without evidence for airway malacia. Thirteen of 236 patients (5.5%) were found to have airway malacia. Most of those affected had lower airway involvement (9/13). The presence of airway malacia was correlated with an increased occurrence of obstructive sleep apnea as well as need for oxygen supplementation, airway surgeries and tracheostomy placement. Although estimates of the frequency of airway malacia in the general population are limited, its frequency in children with achondroplasia appears to be much higher than any published general population estimate. The presence of airway malacia appears to confound other breathing abnormalities in this population and results in the need for more invasive airway treatments. © 2013 Wiley Periodicals, Inc.

  10. Current Care and Investigational Therapies in Achondroplasia.

    Science.gov (United States)

    Unger, Sheila; Bonafé, Luisa; Gouze, Elvire

    2017-04-01

    The goal of this review is to evaluate the management options for achondroplasia, the most common non-lethal skeletal dysplasia. This disease is characterized by short stature and a variety of complications, some of which can be quite severe. Despite several attempts to standardize care, there is still no widely accepted consensus. This is in part due to absence of concrete data on the incidence of sudden unexplained death in infants with achondroplasia and the best investigation for ascertaining which individuals could benefit from foramen magnum decompression surgery. In this review, we identify the different options of care and management for the various orthopedic, neurologic, and respiratory complications. In parallel, several innovative or drug repositioning therapies are being investigated that would restore bone growth but may also prevent complications. Achondroplasia is the most common non-lethal skeletal dysplasia. It is characterized by short stature and a variety of complications, some of which can be quite severe. Despite several attempts to standardize care, there is still no widely accepted consensus. This is in part due to absence of concrete data on the incidence of sudden unexplained death in infants with achondroplasia and the best investigation for ascertaining which individuals could benefit from foramen magnum decompression surgery. In this review, we identify the different options of care and management for the various orthopedic, neurologic, and respiratory complications. In parallel, several innovative or drug repositioning therapies are being investigated that would restore bone growth but may also prevent complications.

  11. Unilateral frontosphenoidal craniosynostosis with achondroplasia: a case report.

    Science.gov (United States)

    Hubbard, Bradley A; Gorski, Jerome L; Muzaffar, Arshad R

    2011-09-01

    Isolated, premature fusion of the frontosphenoidal suture is rare. This report describes an unusual combination of frontosphenoidal craniosynostosis and achondroplasia. Although craniosynostosis is known to occur in allelic conditions such as thanatophoric dysplasia, craniosynostosis in individuals with achondroplasia is exceedingly rare. Due to the distracting diagnosis of achondroplasia or inadequate knowledge of craniosynostosis, the abnormal head shape was initially treated by other physicians with helmet molding. Plastic surgery consultation was obtained at 2 years of age and surgical care was provided. An acceptable head shape was obtained, but the delay in appropriate evaluation was disconcerting. To our knowledge this is the first reported case of isolated frontosphenoidal craniosynostosis associated with achondroplasia.

  12. Sleep disordered breathing in children with achondroplasia.

    Science.gov (United States)

    Zaffanello, Marco; Cantalupo, Gaetano; Piacentini, Giorgio; Gasperi, Emma; Nosetti, Luana; Cavarzere, Paolo; Ramaroli, Diego Alberto; Mittal, Aliza; Antoniazzi, Franco

    2017-02-01

    Children with achondroplasia often have breathing problems, especially during sleep. The most important treatments are adenotonsillectomy (for treating upper obstruction) and/or neurosurgery (for resolving cervicomedullar junction stenosis). We reviewed the scientific literature on polysomnographic investigations which assessed the severity of respiratory disorders during sleep. Recent findings have highlighted the importance of clinical investigations in patients with achondroplasia, differentiating between those that look for neurological patterns and those that look for respiratory problems during sleep. In particular, magnetic resonance imaging (MRI) and somatosensory evoked potentials are the main tools to evaluate necessary neurosurgery and over myelopathy, respectively. The use of polysomnography enables clinicians to identify children with upper airway obstruction and to quantify disease severity; it is not suitable for MRI and/or neurosurgery considerations.

  13. Achondroplasia: anaesthetic challenges for caesarean section.

    Science.gov (United States)

    Dubiel, L; Scott, G A; Agaram, R; McGrady, E; Duncan, A; Litchfield, K N

    2014-08-01

    Pregnancy in women with achondroplasia presents major challenges for anaesthetists and obstetricians. We report the case of a woman with achondroplasia who underwent general anaesthesia for an elective caesarean section. She was 99cm in height and her condition was further complicated by severe kyphoscoliosis and previous back surgery. She was reviewed in the first trimester at the anaesthetic high-risk clinic. A multidisciplinary team was convened to plan her peripartum care. Because of increasing dyspnoea caesarean section was performed at 32weeks of gestation. She received a general anaesthetic using a modified rapid-sequence technique with remifentanil and rocuronium. The intraoperative period was complicated by desaturation and high airway pressures. The woman's postoperative care was complicated by respiratory compromise requiring high dependency care. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Achondroplasia: Craniofacial manifestations and considerations in dental management

    OpenAIRE

    Al-Saleem, Afnan; Al-Jobair, Asma

    2010-01-01

    Achondroplasia is the most common form of skeletal dysplasia dwarfism that manifests with stunted stature and disproportionate limb shortening. Achondroplasia is of dental interest because of its characteristic craniofacial features which include relative macrocephaly, depressed nasal bridge and maxillary hypoplasia. Presence of large head, implanted shunt, airway obstruction and difficulty in head control require special precautions during dental management. Craniofacial manifestations and c...

  15. Ventricular septal defect closure in a patient with achondroplasia.

    Science.gov (United States)

    Nakanishi, Keisuke; Kawasaki, Shiori; Amano, Atsushi

    2017-01-01

    Achondroplasia with co-morbid CHD is rare, as are reports of surgical treatment for such patients. We present the case of a 13-year-old girl with achondroplasia and ventricular septal defect. Her ventricular septal defect was surgically repaired focussing on the cardiopulmonary bypass flow, healing of the sternum, and her frail neck cartilage. The surgery and recovery were without complications.

  16. Mortality in babies with achondroplasia: revisited.

    Science.gov (United States)

    Simmons, Kristen; Hashmi, S Shahrukh; Scheuerle, Angela; Canfield, Mark; Hecht, Jacqueline T

    2014-04-01

    Natural history studies performed 30 years ago identifying higher mortality among children born with achondroplasia, a genetic dwarfing condition, resulted in clinical recommendations aimed at improving mortality in childhood. The objective of this study was to determine if mortality rates have changed over the past few decades. Children born with achondroplasia during 1996 to 2003 were ascertained from the Texas Birth Defects Registry and matched with death certificate data from the Bureau of Vital Statistics through 2007. Infant and overall mortality rates, both crude and standardized to the 2005 (SMR2005 ) and 1975 (SMR1975 ) U.S. populations, were calculated. 106 children born with achondroplasia were identified. Four deaths were reported, with all occurring in the first year of life (mortality rate: 41.4 /1000 live-births). Infant mortality was higher when standardized to the 2005 U.S. population (SMR2005 :6.02, 95% CI:1.64-15.42) than the 1975 population (SMR1975 :2.58, 95% CI:0.70-6.61). The higher SMR2005 compared with SMR1975 , along with the fact that SMR1975 was nearly half that of a previous cohort reported 25 years ago (rate ratio: 0.53, 95% CI: 0.11-2.25), reflect a discrepancy in the changes in mortality in the overall population and in our cohort. Although an overall improvement in mortality, especially after the first year of life, is observed in our cohort, children with achondroplasia are still at a much higher risk of death compared with the general population. A longer follow-up is needed to elucidate whether evaluation/intervention changes have resulted in significant improvement in long-term survival among these patients. Copyright © 2014 Wiley Periodicals, Inc.

  17. Arthroscopic knee anatomy in young achondroplasia patients

    Science.gov (United States)

    del Pilar Duque Orozco, M.; Record, N. C.; Rogers, K. J; Bober, M. B.; Mackenzie, W. G.; Atanda, A.

    2017-01-01

    Abstract Purpose Achondroplasia is the most common form of skeletal dysplasia, affecting more than 250 000 individuals worldwide. In these patients, the developing knee undergoes multiple anatomical changes. The purpose of this study was to characterise the intra-articular knee anatomy in children with achondroplasia who underwent knee arthroscopy. Methods Records of achondroplasia patients who underwent knee arthroscopy between 2009 and 2014 were reviewed. Demographic data, operative reports, follow-up notes, MRI and arthroscopy images were reviewed. Bony, cartilaginous and ligamentous changes were noted. The trochlea sulcus angle was measured from intra-operative arthroscopic images. Results A total of 12 knee arthroscopies in nine patients were performed. The mean age at surgery was 16.9 years (12 to 22). In all patients, the indication for surgery was knee pain and/or mechanical symptoms that were refractory to non-operative treatment. Three anatomical variations involving the distal femur were found in all knees: a deep femoral trochlea; a high A-shaped intercondylar notch; and a vertically oriented anterior cruciate ligament. The average trochlea sulcus angle measured 123°. Pathology included: synovial plica (one knee); chondral lesions (three knees); discoid lateral meniscus (11 knees); and meniscal tears (six knees). All patients were pain-free and returned to normal activity at final follow-up. Conclusion Children with achondroplasia have characteristic distal femur anatomy noted during knee arthroscopy. These variations should be considered normal during knee arthroscopy in these patients. Arthroscopic findings confirmed previous MRI findings within this specific population with the addition of a deep trochlear groove which was not previously reported. PMID:28828058

  18. Circulatory CNP Rescues Craniofacial Hypoplasia in Achondroplasia.

    Science.gov (United States)

    Yamanaka, S; Nakao, Kazumasa; Koyama, N; Isobe, Y; Ueda, Y; Kanai, Y; Kondo, E; Fujii, T; Miura, M; Yasoda, A; Nakao, Kazuwa; Bessho, K

    2017-12-01

    Achondroplasia is the most common genetic form of human dwarfism, characterized by midfacial hypoplasia resulting in occlusal abnormality and foramen magnum stenosis, leading to serious neurologic complications and hydrocephalus. Currently, surgery is the only way to manage jaw deformity, neurologic complications, and hydrocephalus in patients with achondroplasia. We previously showed that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth of long bones and vertebrae and is also a potent stimulator in the craniofacial region, which is crucial for midfacial skeletogenesis. In this study, we analyzed craniofacial morphology in a mouse model of achondroplasia, in which fibroblast growth factor receptor 3 (FGFR3) is specifically activated in cartilage ( Fgfr3 ach mice), and investigated the mechanisms of jaw deformities caused by this mutation. Furthermore, we analyzed the effect of CNP on the maxillofacial area in these animals. Fgfr3 ach mice exhibited midfacial hypoplasia, especially in the sagittal direction, caused by impaired endochondral ossification in craniofacial cartilage and by premature closure of the spheno-occipital synchondrosis, an important growth center in craniomaxillofacial skeletogenesis. We crossed Fgfr3 ach mice with transgenic mice in which CNP is expressed in the liver under the control of the human serum amyloid-P component promoter, resulting in elevated levels of circulatory CNP ( Fgfr3 ach /SAP-Nppc-Tg mice). In the progeny, midfacial hypoplasia in the sagittal direction observed in Fgfr3 ach mice was improved significantly by restoring the thickness of synchondrosis and promoting proliferation of chondrocytes in the craniofacial cartilage. In addition, the foramen magnum stenosis observed in Fgfr3 ach mice was significantly ameliorated in Fgfr3 ach /SAP-Nppc-Tg mice due to enhanced endochondral bone growth of the anterior intraoccipital synchondrosis. These results clearly demonstrate the therapeutic

  19. The neuropsychological function of children with achondroplasia.

    Science.gov (United States)

    Wigg, Kimberley; Tofts, Louise; Benson, Suzanne; Porter, Melanie

    2016-11-01

    The current observational study had three specific objectives: (i) to document any neuropsychological impairment in a sample of children with achondroplasia; (ii) to explore individual variability; and (iii) to determine the functional impact of any impairments. Fourteen children aged between 6 and 15 years with a medically confirmed diagnosis of achondroplasia (FGFR 3 mutation positive) underwent a comprehensive standardized neuropsychological evaluation. On average, while generally still within normal limits, significantly lower scores compared to standardized means were identified on: Full-scale IQ, verbal IQ, working memory, arithmetic, attention, executive functioning and aspects of day-to-day emotional, social, and behavioral functioning. Clinically significant levels of impairment at a group level were identified on measures of: arithmetic, attention, and executive functioning. There was variability among the group and for most measures scores ranged from impaired to within normal limits. A high percentage of children were impaired on measures of: verbal IQ, attention and executive functioning. Results of this study suggest a need for individual neuropsychological evaluation and monitoring of children with achondroplasia and suggest verbal IQ, arithmetic, attention, and executive functioning are particularly common areas of impairment. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Growth hormone treatment in 35 prepubertal children with achondroplasia

    DEFF Research Database (Denmark)

    Hertel, Niels Thomas; Eklöf, Ole; Ivarsson, Sten

    2005-01-01

    BACKGROUND: Achondroplasia is a skeletal dysplasia with extreme, disproportionate, short stature. AIM: In a 5-y growth hormone (GH) treatment study including 1 y without treatment, we investigated growth and body proportion response in 35 children with achondroplasia. METHODS: Patients were rando...... treatment of children with achondroplasia improves height during 4 y of therapy without adverse effect on trunk-leg disproportion. The short-term effect is comparable to that reported in Turner and Noonan syndrome and in idiopathic short stature.......BACKGROUND: Achondroplasia is a skeletal dysplasia with extreme, disproportionate, short stature. AIM: In a 5-y growth hormone (GH) treatment study including 1 y without treatment, we investigated growth and body proportion response in 35 children with achondroplasia. METHODS: Patients were...

  1. Lumbar Nerve Root Occupancy in the Foramen in Achondroplasia

    Science.gov (United States)

    Modi, Hitesh N.; Song, Hae-Ryong; Yang, Jae Hyuk

    2008-01-01

    Lumbar stenosis is common in patients with achondroplasia because of narrowing of the neural canal. However, it is unclear what causes stenosis, narrowing of the central canal or foramina. We performed a morphometric analysis of the lumbar nerve roots and intervertebral foramen in 17 patients (170 nerve roots and foramina) with achondroplasia (eight symptomatic, nine asymptomatic) and compared the data with that from 20 (200 nerve roots and foramina) asymptomatic patients without achondroplasia presenting with low back pain without neurologic symptoms. The measurements were made on left and right parasagittal MRI scans of the lumbar spine. The foramen area and root area were reduced at all levels from L1 to L5 between the patients with achondroplasia (Groups I and II) and the nonachondroplasia group (Group III). The percentage of nerve root occupancy in the foramen between Group I and Group II as compared with the patients without achondroplasia was similar or lower. This implied the lumbar nerve root size in patients with achondroplasia was smaller than that of the normal population and thus there is no effective nerve root compression. Symptoms of lumbar stenosis in achondroplasia may be arising from the central canal secondary to degenerative disc disease rather than a true foraminal stenosis. Level of Evidence: Level I, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18259829

  2. Prenatal Diagnosis of Concurrent Achondroplasia and Klinefelter Syndrome

    Directory of Open Access Journals (Sweden)

    Esther Perez-Carbajo

    2015-01-01

    Full Text Available Achondroplasia is the most frequent nonlethal skeletal dysplasia, with a prevalence of 1 : 5000 to 1 : 40,000 live births, and it is caused by a fibroblast growth factor receptor alteration. The combination of achondroplasia and Klinefelter syndrome is extremely rare and just four reports have been published in the literature, which were all diagnosed postnatally. We report the fifth case described of this uncommon association and its prenatal diagnosis. In cases of prenatal diagnosis of achondroplasia with additional suspicious morphological abnormalities, an invasive test such as amniocentesis must be carried out to assess the karyotype normality.

  3. Successful Delivery in a Woman With Achondroplasia: A Case Report

    Directory of Open Access Journals (Sweden)

    Mahbooheh Shirazi

    2017-10-01

    Full Text Available Achondroplasia is an autosomal dominant disease which is characterized by limb shortening and narrow trunk, and macrocephaly. Women with achondroplasia suffer from infertility, menorrhagia, dysmenorrhoea, leiomyomata and early menopause. Our case was a 26-year-old woman with achondroplasia who had scoliosis and osteoporosis. She referred to our clinic at 9 weeks of gestation and had all screenings completely. She had a single female fetus with no abnormalities. She had an emergent due to rupture of membranes at 37 weeks and 3 days under general anesthesia. The neonate had no complications. The first minute Apgar score was 9 and 5th-minute Apgar score were 10. Umbilical artery Ph was 7.26 and birth weight was 3140. A woman with achondroplasia could have a normal pregnancy and give birth to a healthy term neonate under precise screening.

  4. Successful Delivery in a Woman With Achondroplasia: A Case Report.

    Science.gov (United States)

    Shirazi, Mahbooheh; Golshahi, Fateme; Teimoory, Nastaran

    2017-08-01

    Achondroplasia is an autosomal dominant disease which is characterized by limb shortening and narrow trunk, and macrocephaly. Women with achondroplasia suffer from infertility, menorrhagia, dysmenorrhoea, leiomyomata and early menopause. Our case was a 26-year-old woman with achondroplasia who had scoliosis and osteoporosis. She referred to our clinic at 9 weeks of gestation and had all screenings completely. She had a single female fetus with no abnormalities. She had an emergent due to rupture of membranes at 37 weeks and 3 days under general anesthesia. The neonate had no complications. The first minute Apgar score was 9 and 5th-minute Apgar score were 10. Umbilical artery Ph was 7.26 and birth weight was 3140. A woman with achondroplasia could have a normal pregnancy and give birth to a healthy term neonate under precise screening.

  5. Management of disabilities associated with achondroplasia.

    Science.gov (United States)

    Haga, Nobuhiko

    2004-01-01

    Achondroplasia is a skeletal dysplasia that manifests as short stature. Impairment and complications range over many disciplines including orthopedics, pediatrics, neurology, and otolaryngology. The major impairments of the extremities are short limbs, limited elbow and hip extension, and knee and leg deformities that can cause disabilities in arm function and locomotion. Hydrocephalus, a narrow foramen magnum, spinal deformity, and spinal canal stenosis can cause neurological problems, leading to disabilities in locomotion, communication, and learning. Malfunctions of the otolaryngeal system such as otitis media, upper respiratory obstruction, deafness, speech delay, and malocclusion are interrelated and can also lead to disabilities in communication and learning. Although such disabilities may cause social handicaps, most children receive a normal education. Their social maturity scale is comparable to that of normal children, but their scale of locomotion is not. The reported occupational level of female adult patients is lower than that of their unaffected siblings. When managing patients, orthopedists should consider the overall aspects of achondroplasia, including natural development and complications other than orthopedic factors.

  6. Limb Lengthening in Patients with Achondroplasia.

    Science.gov (United States)

    Park, Kwang-Won; Garcia, Rey-an Niño; Rejuso, Chastity Amor; Choi, Jung-Woo; Song, Hae-Ryong

    2015-11-01

    Although bilateral lower-limb lengthening has been performed on patients with achondroplasia, the outcomes for the tibia and femur in terms of radiographic parameters, clinical results, and complications have not been compared with each other. We proposed 1) to compare the radiological outcomes of femoral and tibial lengthening and 2) to investigate the differences of complications related to lengthening. We retrospectively reviewed 28 patients (average age, 14 years 4 months) with achondroplasia who underwent bilateral limb lengthening between 2004 and 2012. All patients first underwent bilateral tibial lengthening, and at 9-48 months (average, 17.8 months) after this procedure, bilateral femoral lengthening was performed. We analyzed the pixel value ratio (PVR) and characteristics of the callus of the lengthened area on serial radiographs. The external fixation index (EFI) and healing index (HI) were computed to compare tibial and femoral lengthening. The complications related to lengthening were assessed. The average gain in length was 8.4 cm for the femur and 9.8 cm for the tibia. The PVR, EFI, and HI of the tibia were significantly better than those of the femur. Fewer complications were found during the lengthening of the tibia than during the lengthening of the femur. Tibial lengthening had a significantly lower complication rate and a higher callus formation rate than femoral lengthening. Our findings suggest that bilateral limb lengthening (tibia, followed by femur) remains a reasonable option; however, we should be more cautious when performing femoral lengthening in selected patients.

  7. Achondroplasia: Current Options and Future Perspective.

    Science.gov (United States)

    Bouali, Houda; Latrech, Hanane

    2015-06-01

    Achondroplasia is a human bone genetic disorder of the growth plate and is the most common form of inherited disproportionate short stature. It is inherited as an autosomal dominant disease with essentially complete penetrance. Of these most have the same point mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) which is a negative regulator of bone growth. The clinical and radiological features of achondroplasia can easily be identified; they include disproportionate short stature with rhizomelic shortening, macrocephaly with frontal bossing, midface hypoplasia, lumbar hyperlordosis, and a trident hand configuration. The majority of achondroplasts have a normal intelligence, but many social and medical complications may compromise a full and productive life. Some of them have serious health consequences related to hydrocephalus, craniocervical junction compression, or upper-airway obstruction. In this article, we discuss a number of treatments from the surgical limb lengthening approach and the Recombinant Growth Hormone (rhGH) treatment, to future treatments, which include the Natriuretic Peptide C-type (CNP). The discussion is a comparative study of the complications and drawbacks of various experiments using numerous strategies.

  8. Avascular Retinal Findings in a Child With Achondroplasia.

    Science.gov (United States)

    Hua, Hong-Uyen T; Tran, Kimberly D; Medina, Carlos A; Fallas, Brenda; Negron, Cathy; Berrocal, Audina M

    2017-03-01

    The authors present clinical and angiographic findings in a 12-year-old girl with achondroplasia who presented with bilateral retinal peripheral nonperfusion and unilateral rhegmatogenous retinal detachment, which has not been previously described in achondroplasia. This report contributes incremental knowledge regarding aberrant retinal vascular phenomena observed in pediatric disease states and implicates the possible role of mutations in the FGFR3 gene in peripheral vascular abnormalities. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:272-274.]. Copyright 2017, SLACK Incorporated.

  9. Achondroplasia with multiple-suture craniosynostosis: a report of a new case of this rare association

    NARCIS (Netherlands)

    Bessenyei, Beáta; Nagy, Andrea; Balogh, Erzsébet; Novák, László; Bognár, László; Knegt, Alida C.; Oláh, Eva

    2013-01-01

    We report on a female patient with an exceedingly rare combination of achondroplasia and multiple-suture craniosynostosis. Besides the specific features of achondroplasia, synostosis of the metopic, coronal, lambdoid, and squamosal sutures was found. Series of neurosurgical interventions were

  10. A case of chorioretinal coloboma in a patient with achondroplasia.

    Science.gov (United States)

    Yoo, Woong Sun; Park, Yeon Jung; Yoo, Ji Myung

    2010-10-01

    Achondroplasia is a congenital disorder resulting from a specific disturbance in endochondral bone formation. The ophthalmic features reportedly associated with achondroplasia are telecanthus, exotropia, inferior oblique overaction, angle anomalies and cone-rod dystrophy. This is first report of chorioretinal coloboma in achondroplasia. An 8-year-old female was diagnosed with a developmental delay, known as achondroplasia, seven months after birth. Upon her initial visit, visual acuity was 0.3 in both eyes. The patient had telecanthus but normal ocular motility. Findings were normal upon anterior segment examination. Fundus examination of both eyes revealed about 1,500 µm sized chorioretinal coloboma inferior to the optic nerve head. Upon fluorescent angiography, there was chorioretinal coloboma without any other lesions. Afterward, there was no change in the fundus lesion, and best corrected visual acuity was 0.6 in both eyes. Chorioretinal coloboma is associated with choroidal and retinal detachment. As chorioretinal coloboma and achondroplasia are developmental disorders in the embryonic stage, early detection and regular ophthalmologic examination would be essential in patients with achondroplasia.

  11. Achondroplasia Presenting with Pneumonia in a Two Months Old Boy

    Directory of Open Access Journals (Sweden)

    Huseyin Bilgin

    2014-03-01

    Full Text Available Achondroplasia is one of the common chondrodysplasias with an inheritance is autosomal dominant, but in around 85% the phenotype is the result of a new mutation. Achondroplasia develops as a result of dysplasia of enchondral formation due to the mutation of fibroblast growth factor receptor 3. A 2-month-old boy was referred to the our hospital with cough and fever. Craniofacially the head appeared large and also frontal bossing and depressed nasal bridge was demonstrated. Narrow lumbar interpedicular distances, normal trunk length, short-wide pelvis, micromelic upper extremities and rhizomelic lower extremities were seen on x-ray examination. The clinically and radiographically diagnosis of achondroplasia with heart failure secondary to pneumonia was performed. Achondroplasia, presenting with respiratory disorders and short limb should be differentiated from metatropic dysplasia and campomelic dysplasia. Achondroplasia may had similar findings with other dwarfism and differentiate diagnosis from other achondroplasia like diseases needs team work which includes pediatry, radiology and medical genetic for better patient care and family counseling.

  12. Two sibs who are double heterozygotes for achondroplasia and pseudoachondroplastic dysplasia.

    OpenAIRE

    Woods, C G; Rogers, J G; Mayne, V

    1994-01-01

    We report a family in which two sibs have both achondroplasia and pseudoachondroplastic dysplasia. The mother has achondroplasia and the father has pseudoachondroplastic dysplasia, which he had inherited from his father. Both children appeared typical of achondroplasia at birth. By 1 1/2 years they had developed a fixed lumbar kyphosis with gibbus and had additional x ray changes unusual for just achondroplasia and suggestive of pseudoachondroplastic dysplasia. Subsequently both children have...

  13. Advances in research on and diagnosis and treatment of achondroplasia in China

    OpenAIRE

    Wang, Yao; Liu, Zeying; Liu, Zhenxing; Zhao, Heng; Zhou, Xiaoyan; Cui, Yazhou; Han, Jinxiang

    2013-01-01

    Achondroplasia is a rare autosomal dominant genetic disease. Research on achondroplasia in China, however, has received little emphasis. Around 80–90% of cases of neonatal achondroplasia result from mutations in fibroblast growth factor receptor 3 (FGFR3) according to polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Recently, genetic research on achondroplasia in China made a major breakthrough by revealing two novel mutations located on the FGFR3 gene, thus helpi...

  14. Growth charts for Australian children with achondroplasia.

    Science.gov (United States)

    Tofts, Louise; Das, Sandeep; Collins, Felicity; Burton, Karen L O

    2017-08-01

    Achondroplasia is an autosomal dominant disorder, the most common genetic cause of short stature in humans. Reference curves for head circumference, weight, height, and BMI are needed in clinical practice but none exist for the Australian population. This study aimed to produce head circumference, height, weight, and BMI reference percentile curves for Australian children and adolescents with achondroplasia. Measurements of head circumference, height and weight taken at clinical visits were retrospectively extracted from the electronic medical record. Age was corrected for prematurity. Patients were excluded from head circumference analysis if they had significant neurosurgical complications and from the weight and BMI analysis when they had a clinical diagnosis of overweight. Measurements were available on 138 individuals (69 males and 69 females) taken between 1970 and 2015, with over 50% collected since 2005. A total of 3,352 data points were available. The LMS method was used to produce growth charts with estimated centiles (10, 25, 50, 75, and 90th) separately for males and females. For females birth weight was 3 kg (2.5-3.5 kg), birth length 48 cm (44-50 cm) and head circumference 37.5 cm (36-39 cm), adult height was 125 cm (116-132 cm), weight 42 kg (34-54 kg), and head circumference 58 cm (55.5-60.5 cm) all 50th centile (10-90th). For males birth weight was 3.5 kg (3-4 kg), length 49 cm (46-52 cm) and head circumference 38.5 cm (36-41 cm), adult height was 134 cm (125-141 cm), weight 41 kg (24.5-57 kg) and head circumference 61 cm (58-64 cm). The curves are similar to previously published reference data from the USA and have expected population wide variation from curves from an Argentinian population. Despite limitations of our curves for adolescents (12 years and older) due to data paucity, these Australian growth charts for children and adolescents with achondroplasia will be a useful reference in clinical

  15. Advances in research on and diagnosis and treatment of achondroplasia in China

    Science.gov (United States)

    Wang, Yao; Liu, Zeying; Liu, Zhenxing; Zhao, Heng; Zhou, Xiaoyan; Cui, Yazhou; Han, Jinxiang

    2013-01-01

    Summary Achondroplasia is a rare autosomal dominant genetic disease. Research on achondroplasia in China, however, has received little emphasis. Around 80–90% of cases of neonatal achondroplasia result from mutations in fibroblast growth factor receptor 3 (FGFR3) according to polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Recently, genetic research on achondroplasia in China made a major breakthrough by revealing two novel mutations located on the FGFR3 gene, thus helping to complete the pathological molecular map of achondroplasia. There are still, however, unknown aspects of the diagnosis and treatment of achondroplasia. This review will summarize advances in research on and the clinical diagnosis and treatment of achondroplasia in China. PMID:25343101

  16. Development in Children with Achondroplasia: A Prospective Clinical Cohort Study

    Science.gov (United States)

    Ireland, Penelope J.; Donaghey, Samantha; McGill, James; Zankl, Andreas; Ware, Robert S.; Pacey, Verity; Ault, Jenny; Savarirayan, Ravi; Sillence, David; Thompson, Elizabeth; Townshend, Sharron; Johnston, Leanne M.

    2012-01-01

    Aim: Achondroplasia is characterized by delays in the development of communication and motor skills. While previously reported developmental profiles exist across gross motor, fine motor, feeding, and communication skills, there has been no prospective study of development across multiple areas simultaneously. Method: This Australasian…

  17. Sleep and upper airway obstruction in children with achondroplasia

    NARCIS (Netherlands)

    Zucconi, M; Weber, G; Castronovo, [No Value; FeriniStrambi, L; Russo, F; Chiumello, G; Smirne, S

    Objective: The features of achondroplasia, the most common form of dwarfism, includes short cranial base and midface hypoplasia; both abnormalities increased the risk of upper airway obstruction during sleep, The aim of our study was to evaluate sleep and respiratory function of children with

  18. Functional Performance in Young Australian Children with Achondroplasia

    Science.gov (United States)

    Ireland, Penelope Jane; McGill, James; Zankl, Andreas; Ware, Robert S.; Pacey, Verity; Ault, Jenny; Savarirayan, Ravi; Sillence, David; Thompson, Elizabeth M.; Townshend, Sharron; Johnston, Leanne Marie

    2011-01-01

    Aim: The aim of this study was to determine population-specific developmental milestones for independence in self-care, mobility, and social cognitive skills in children with achondroplasia, the most common skeletal dysplasia. Methods: Population-based recruitment from October 2008 to October 2010 identified 44 Australian children with…

  19. Polycystic kidney disease in a patient with achondroplasia ...

    African Journals Online (AJOL)

    Autosomal dominant polycystic kidney disease is a multisystem disease involving many organs. An association with other diseases such as tuberous sclerosis, von Hippel-Lindau disease and Marfan syndrome have been previously described. We describe a 35 year old female with achondroplasia who developed ...

  20. Sleep and upper airway obstruction in children with achondroplasia

    NARCIS (Netherlands)

    Zucconi, M; Weber, G; Castronovo, [No Value; FeriniStrambi, L; Russo, F; Chiumello, G; Smirne, S

    1996-01-01

    Objective: The features of achondroplasia, the most common form of dwarfism, includes short cranial base and midface hypoplasia; both abnormalities increased the risk of upper airway obstruction during sleep, The aim of our study was to evaluate sleep and respiratory function of children with

  1. Specific force of the vastus lateralis in adults with achondroplasia.

    Science.gov (United States)

    Sims, David T; Onambélé-Pearson, Gladys L; Burden, Adrian; Payton, Carl; Morse, Christopher I

    2018-03-01

    Achondroplasia is a clinical condition defined by shorter stature and disproportionate limb length. Force production in able-bodied individuals (controls) is proportional to muscle size, but given the disproportionate nature of achondroplasia, normalizing to anatomical cross-sectional area (ACSA) is inappropriate. The aim of this study was to assess specific force of the vastus lateralis (VL) in 10 adults with achondroplasia (22 ± 3 yr) and 18 sex-matched controls (22 ± 2 yr). Isometric torque (iMVCτ) of the dominant knee extensors (KE) and in vivo measures of VL muscle architecture, volume, activation, and patella tendon moment arm were used to calculate VL physiological CSA (PCSA), fascicle force, and specific force in both groups. Achondroplasic muscle volume was 53% smaller than controls (284 ± 36 vs. 604 ± 102 cm 3 , P 0.05), but coactivation of bicep femoris of achondroplasic subjects was 70% more than controls (43 ± 20 vs. 13 ± 5%, P force (702 ± 235 vs. 1704 ± 303 N, P force than control subjects (17 ± 6 vs. 24 ± 6 N⋅cm -2 , P = 0.012). The smaller VL specific force in achondroplasia may be attributed to infiltration of fat and connective tissue, rather than to any difference in myofilament function. NEW & NOTEWORTHY The novel observation of this study was the measurement of normalized force production in a group of individuals with disproportionate limb length-to-torso ratios.

  2. Association of achondroplasia with sagittal synostosis and scaphocephaly in two patients, an underestimated condition?

    Science.gov (United States)

    Accogli, Andrea; Pacetti, Mattia; Fiaschi, Pietro; Pavanello, Marco; Piatelli, Gianluca; Nuzzi, Daniele; Baldi, Maurizia; Tassano, Elisa; Severino, Maria Savina; Allegri, Anna; Capra, Valeria

    2015-03-01

    We report on two patients with an unusual combination of achondroplasia and surgically treated sagittal synostosis and scaphocephaly. The most common achondroplasia mutation, p.Gly380Arg in fibroblast growth factor receptor 3 (FGFR3), was detected in both patients. Molecular genetic testing of FGFR1, FGFR2, FGFR3 and TWIST1 genes failed to detect any additional mutations. There are several reports of achondroplasia with associated craniosynostosis, but no other cases of scaphocephaly in children with achondroplasia have been described. Recently it has been demonstrated that FGFR3 mutations affect not only endochondral ossification but also membranous ossification, providing new explanations for the craniofacial hallmarks in achondroplasia. Our report suggests that the association of isolated scaphocephaly and other craniosynostoses with achondroplasia may be under recognized. © 2015 Wiley Periodicals, Inc.

  3. Diffusion tensor imaging of the brainstem in children with achondroplasia.

    Science.gov (United States)

    Bosemani, Thangamadhan; Orman, Gunes; Carson, Kathryn A; Meoded, Avner; Huisman, Thierry A G M; Poretti, Andrea

    2014-11-01

    The aims of this study were to compare, using diffusion tensor imaging (DTI) of the brainstem, microstructural integrity of the white matter in children with achondroplasia and age-matched participants and to correlate the severity of craniocervical junction (CCJ) narrowing and neurological findings with DTI scalars in children with achondroplasia. This study also aimed to assess the potential role of fibroblast growth factor receptor type 3 on white matter microstructure. Diffusion tensor imaging was performed using a 1.5T magnetic resonance scanner and balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements were obtained from regions of interest, sampled in each pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle, as well as in the lower brainstem and centrum semiovale, for fractional anisotropy and for mean, axial, and radial diffusivity. In addition, a severity score for achondroplasia was assessed by measuring CCJ narrowing. Eight patients with achondroplasia (seven males, one female; mean age 5y 6mo, range 1y 1mo-15y 1mo) and eight age- and sex-matched comparison participants (mean age 5y 2mo, range 1y 1mo-14y 11mo) were included in this study. Fractional anisotropy was lower and mean diffusivity and radial diffusivity were higher in the lower brainstem of patients with achondroplasia than in age-matched comparison participants. The CST and middle cerebellar peduncle of the participants showed increases in mean, axial, and radial diffusivity. Fractional anisotropy in the lower brainstem was negatively correlated with the degree of CCJ narrowing. No differences in the DTI metrics of the centrum semiovale were observed between the two groups. The reduction in fractional anisotropy and increase in diffusivities in the lower brainstem of participants with achondroplasia may reflect secondary encephalomalacic degeneration and cavitation of the affected white matter tracts as shown by histology. In

  4. Achondroplasia and Down syndrome in the same patient. Report of a case

    International Nuclear Information System (INIS)

    Sanchez, O; Guerra, D; Nastasi, J; Escalona, J

    1999-01-01

    Achondroplasia and trisomy 21 are, within their respective categories, conditions the most frequent genetic diseases found in newborns. The simultaneous presence of both conditions in the same patient, has been however, reported only once in the world literature. In this paper we present a patient affected by both entities (Achondroplasia and Trisomy 21). The clinical findings (using, among other, achondroplasia radiography), and the reasons for the rare reported frequency of these cases are discussed

  5. Advances in treatment of achondroplasia and osteoarthritis.

    Science.gov (United States)

    Klag, Kendra A; Horton, William A

    2016-04-15

    Achondroplasia (ACH) is the prototype and most common of the human chondrodysplasias. It results from gain-of-function mutations that exaggerate the signal output of the fibroblast growth factor receptor 3 (FGFR3), a receptor tyrosine kinase that negatively regulates growth plate activity and linear bone growth. Several approaches to reduce FGFR3 signaling by blocking receptor activation or inhibiting downstream signals have been proposed. Five show promise in preclinical mouse studies. Two candidate therapies target the extracellular domain of FGFR3. The first is a decoy receptor that competes for activating ligands. The second is a synthetic blocking peptide that prevents ligands from binding and activating FGFR3. Two established drugs, statins and meclozine, improve growth of ACH mice. The strongest candidate therapy employs an analog of C-type natriuretic peptide (CNP), which antagonizes the mitogen-activated-protein (MAP) kinase pathway downstream of the FGFR3 receptor and may also act independently in the growth plate. Only the CNP analog has reached clinical trials. Preliminary results of Phase 2 studies show a substantial increase in growth rate of ACH children after six months of therapy with no serious adverse effects. A challenge for drug therapy in ACH is targeting agents to the avascular growth plate. The application of gene therapy in osteoarthritis offers insights because it faces similar technical obstacles. Major advances in gene therapy include the emergence of recombinant adeno-associated virus as the vector of choice, capsid engineering to target vectors to specific tissues, and development of methods to direct vectors to articular chondrocytes. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Cardiopulmonary exercise capacity, muscle strength, and physical activity in children and adolescents with achondroplasia

    NARCIS (Netherlands)

    Takken, Tim; van Bergen, Monique W. M.; Sakkers, Ralph J. B.; Helders, Paul J. M.; Engelbert, Raoul H. H.

    2007-01-01

    To study in children with achondroplasia the response to exercise and muscle strength compared with healthy peers and to describe the relation between exercise capacity, anthropometric factors, and physical activity. Patients (7 boys and 10 girls; mean age, 11.8 +/- 3.3 years) with achondroplasia

  7. Non-invasive prenatal detection of achondroplasia using circulating fetal DNA in maternal plasma.

    Science.gov (United States)

    Lim, Ji Hyae; Kim, Mee Jin; Kim, Shin Young; Kim, Hye Ok; Song, Mee Jin; Kim, Min Hyoung; Park, So Yeon; Yang, Jae Hyug; Ryu, Hyun Mee

    2011-02-01

    To perform a reliable non-invasive detection of the fetal achondroplasia using maternal plasma. We developed a quantitative fluorescent-polymerase chain reaction (QF-PCR) method suitable for detection of the FGFR3 mutation (G1138A) causing achondroplasia. This method was applied in a non-invasive detection of the fetal achondroplasia using circulating fetal-DNA (cf-DNA) in maternal plasma. Maternal plasmas were obtained at 27 weeks of gestational age from women carrying an achondroplasia fetus or a normal fetus. Two percent or less achondroplasia DNA was reliably detected by QF-PCR. In a woman carrying a normal fetus, analysis of cf-DNA showed only one peak of the wild-type G allele. In a woman expected an achondroplasia fetus, analysis of cf-DNA showed the two peaks of wild-type G allele and mutant-type A allele and accurately detected the fetal achondroplasia. The non-invasive method using maternal plasma and QF-PCR may be useful for diagnosis of the fetal achondroplasia.

  8. Surgical treatment for cervicomedullary compression among infants with achondroplasia.

    Science.gov (United States)

    Shimony, Nir; Ben-Sira, Liat; Sivan, Yakov; Constantini, Shlomi; Roth, Jonathan

    2015-05-01

    Achondroplasia is the most common form of dwarfism. Respiratory failure is responsible for most deaths among these children and is often related to cervicomedullary compression (CMC). We present our experience with early cervicomedullary decompression in infants with achondroplasia. Data was retrospectively collected for infants with achondroplasia who underwent CMC decompression between 1998 and 2013. Data included presurgical and postsurgical neurological examinations, MRI scans, and sleep study results. Ten infants were included. Ages at surgery were 4 to 23 months (12.5 ± 6.88 months). All infants displayed neurological findings prior to surgery, although often subtle. All infants underwent a foramen magnum opening with a wide C1 laminectomy. Following surgery, seven patients (70 %) demonstrated improved neurological status, and one displayed neurological deterioration. Seven patients demonstrated improved sleep quality 1 year after surgery. These patients had a good or improved neurological status following surgery. Preoperative radiological findings included abnormal hyperintense T2 changes in all children (improved following surgery in six children), brainstem distortion in four children (improved in all), and diminished cerebrospinal fluid (CSF) spaces at the level of the foramen magnum in eight children (improved in seven). One child with extensive preoperative T2 changes accompanied by neurological and respiratory decline, deteriorated following surgery, and remains chronically ventilated. Infants with achondroplasia are prone to neurological and respiratory symptoms. We believe that early diagnosis and early surgery for decompression of the foramen magnum and C1 lamina can alleviate respiratory symptoms, improve neurological status, and perhaps prevent sudden infant death in this population.

  9. Achondroplasia-hypochondroplasia complex and abnormal pulmonary anatomy.

    Science.gov (United States)

    Bober, Michael B; Taylor, Megan; Heinle, Robert; Mackenzie, William

    2012-09-01

    Achondroplasia and hypochondroplasia are two of the most common forms of skeletal dysplasia. They are both caused by activating mutations in FGFR3 and are inherited in an autosomal dominant manner. Our patient was born to parents with presumed achondroplasia, and found on prenatal testing to have p.G380R and p.N540K FGFR3 mutations. In addition to having typical problems associated with both achondroplasia and hypochondroplasia, our patient had several atypical findings including: abnormal lobulation of the lungs with respiratory insufficiency, C1 stenosis, and hypoglycemia following a Nissen fundoplication. After his reflux and aspiration were treated, the persistence of the tachypnea and increased respiratory effort indicated this was not the primary source of the respiratory distress. Our subsequent hypothesis was that primary restrictive lung disease was the cause of his respiratory distress. A closer examination of his chest circumference did not support this conclusion either. Following his death, an autopsy found the right lung had 2 lobes while the left lung had 3 lobes. A literature review demonstrates that other children with achondroplasia-hypochondroplasia complex have been described with abnormal pulmonary function and infants with thanatophoric dysplasia have similar abnormal pulmonary anatomy. We hypothesize that there may be a primary pulmonary phenotype associated with FGFR3-opathies, unrelated to chest size which leads to the consistent finding of increased respiratory signs and symptoms in these children. Further observation of respiratory status, combined with the macroscopic and microscopic analysis of pulmonary branching anatomy and alveolar structure in this patient population will be important to explore this hypothesis. Copyright © 2012 Wiley Periodicals, Inc.

  10. Physeal growth arrest after tibial lengthening in achondroplasia

    Science.gov (United States)

    2012-01-01

    Background and purpose Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with acondroplasia. Methods We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who underwent bilateral tibial lengthening before skeletal maturity (lengthening group L) and 12 achondroplasia patients of similar height and age who did not undergo tibial lengthening (control group C). The mean amount of lengthening of tibia in group L was 9.2 cm (lengthening percentage: 60%) and the mean age at the time of lengthening was 8.2 years. The mean duration of follow-up was 9.8 years. Results Skeletal maturity (fusion of physis) occurred at 15.2 years in group L and at 16.0 years in group C. The actual length of tibia (without distraction) at skeletal maturity was 238 mm in group L and 277 mm in group C (p = 0.03). The mean growth rates showed a decrease in group L relative to group C from about 2 years after surgery. Physeal closure was most pronounced on the anterolateral proximal tibial physis, with relative preservation of the distal physis. Interpretation Our findings indicate that physeal growth rate can be disturbed after tibial lengthening in achondroplasia, and a close watch should be kept for such an occurrence—especially when lengthening of more than 50% is attempted. PMID:22489887

  11. Concomitant achondroplasia and developmental dysplasia of the hip

    OpenAIRE

    Malcolm, Tennison L.; Phan, Duy L.; Schwarzkopf, Ran

    2015-01-01

    Achondroplasia (ACH) is the most common form of hereditary dwarfism and presents with multiple musculoskeletal anomalies but is not normally associated with premature hip arthritis. Developmental dysplasia of the hip (DDH) is a spectrum of disease resulting in shallow acetabular depth and a propensity for chronic femoral subluxation or dislocation; it is among the most common causes of premature arthritis. This case report describes the diagnosis of symptomatic DDH in a patient with ACH and h...

  12. The sagging rope sign in achondroplasia - different from Perthes' disease

    International Nuclear Information System (INIS)

    Shingade, Viraj U.; Song, Hae-Ryong; Lee, Seok-Hyun; Suh, Seung-Woo; Oh, Chang-Wug; Hong, Jun-Seok

    2006-01-01

    The sagging rope sign is a radio-opaque line, seen on radiographs of the hips, with Perthes' disease. The main purpose of this study was to determine the incidence, cause and importance of this sign in achondroplasia, and to reveal how it differs from in Perthes' disease. Serial radiograms, along with 2-dimensional and 3-dimensional CT images were studied in 42 achondroplasic patients. Forty-two achondroplasic patients, reported at our institute (for routine outpatient consultation, spine surgeries, deformity corrections, limb-lengthening procedures) were included in this study. There were 26 males and 16 females. The sign was observed bilaterally, in all patients. Evaluation of CT images revealed spherical heads, with presence of circumferential overhang in all hips. This circumferential overhang, seen on 3-D CT scan, corresponded to the sagging rope sign on radiographs. Presence of the sagging rope sign in bilateral hips is a characteristic feature of achondroplasia. It usually appears before epiphyseal closure. Its cause, incidence, and nature differ from Perthes' disease, and its presence does not carry a bad prognosis in achondroplasia. (orig.)

  13. Two sibs who are double heterozygotes for achondroplasia and pseudoachondroplastic dysplasia.

    Science.gov (United States)

    Woods, C G; Rogers, J G; Mayne, V

    1994-01-01

    We report a family in which two sibs have both achondroplasia and pseudoachondroplastic dysplasia. The mother has achondroplasia and the father has pseudoachondroplastic dysplasia, which he had inherited from his father. Both children appeared typical of achondroplasia at birth. By 1 1/2 years they had developed a fixed lumbar kyphosis with gibbus and had additional x ray changes unusual for just achondroplasia and suggestive of pseudoachondroplastic dysplasia. Subsequently both children have shown characteristic features of both conditions and have grown less well than expected for achondroplasia. Radiographs show the striking synergistic effects of the two conditions. MRI in both sibs confirmed brain stem compression at the foramen magnum. This may be an important complication and should be actively sought in any double heterozygote. Images PMID:7966194

  14. Leg length, sitting height, and body proportions references for achondroplasia: New tools for monitoring growth.

    Science.gov (United States)

    Del Pino, Mariana; Ramos Mejía, Rosario; Fano, Virginia

    2018-04-01

    Achondroplasia is the most common form of inherited disproportionate short stature. We report leg length, sitting height, and body proportion curves for achondroplasia. Seven centile format of sitting height, leg length, sitting height/leg length ratio, sitting height/height ratio, and head circumference/height ratio were estimated by the LMS method. The Q-test was applied to assess the goodness of fit. For comparison, centiles of sitting height and leg length were graphed using Argentine national growth references for achondroplasia and non-achondroplasia populations. The sample consisted of 342 children with achondroplasia (171 males, 171 females) aged 0-18 years. The median (interquartile range) number of measurements per child was 6 (3, 12) for sitting height and 8 (3, 13) for head circumference. Median leg length increased from 14 cm at age 1 week to 44 and 40 cm (males and females, respectively) in achondroplasia adolescents which is 3.5 cm shorter than non-achondroplasia children at age 1 week and, 38 cm shorter at adolescence. Median sitting height increased from 34 cm at birth to 86 and 81 in adolescents' boys and girls respectively, only 5 cm shorter than non-achondroplasia children. Sitting height/leg length decreased from 2.61 at birth to approximately 1.90 at adolescent. Median head circumference/height ratio decreased from 0.79 at birth to 0.46 at 18 years in both sexes. Growth of lower limbs is affected early in life and becomes more noticeable throughout childhood. The disharmonic growth between the less affected trunk and the severely affected limbs determine body disproportion in achondroplasia. © 2018 Wiley Periodicals, Inc.

  15. Fixator-Assisted Lengthening and Deformity Correction Over an Intramedullary Nail in a Patient with Achondroplasia

    Directory of Open Access Journals (Sweden)

    Erdal Uzun

    2016-05-01

    Full Text Available Achondroplasia is the most frequently encountered form of nonlethal skeletal dysplasia and a type of rhizomelic dwarfism. It results in considerable physical and psychologic handicaps owing to the disproportionate stature of the body and difficulty in performing routine activities of daily living. They also have major musculoskeletal problems including symptomatic malalignment of the lower limbs. Limb lengthening has been used in patients with achondroplasia by different techniques (Intramedullar nailing, monolateral or circular external fixator. We report our treatment of a patient 17 years of age with achondroplasia for bilateral lower limb length discrepancy and bilateral tibial varus deformity.

  16. Coronary artery surgery in a man with achondroplasia: a case report

    Directory of Open Access Journals (Sweden)

    Daskalopoulos Marios E

    2010-10-01

    Full Text Available Abstract Introduction Achondroplasia is a musculoskeletal disorder associated with short stature. Despite an estimated prevalence of 1:25,000 in the general population, there is little literature concerning the diagnostic and treatment challenges faced by doctors dealing with a heart operation on a patient with this condition. Case presentation We present the case of a 41-year-old Caucasian man of Greek ethnicity with achondroplasia, who underwent bypass heart surgery. Conclusions The surgery was successful and did not present particular difficulties, showing that heart surgery can be safely performed on people with achondroplasia.

  17. Nonrandom association of a type II procollagen genotype with achondroplasia

    OpenAIRE

    1986-01-01

    Achondroplasia is an autosomal dominant disorder that involves defective endochondral bone formation. Type II collagen is the predominant collagen of cartilage. We found a HindIII polymorphic site in the normal Caucasian population by using the type II procollagen gene probe pgHCol(II)A. The presence of this site yields a 7.0-kilobase (kb) band; its absence yields a 14.0-kb band. We found a significant deviation in genotype distribution and allele frequencies in a population of unrelated indi...

  18. Correction of anterior open bite in a case of achondroplasia

    Directory of Open Access Journals (Sweden)

    Karpagam S

    2005-01-01

    Full Text Available Treatment planning for patients with skeletal deformities is often considered challenging. This article reports a female patient with achondroplasia who presented with severe maxillary retrognathism and vertical excess along with anterior open bite. The clinical and cephalometric findings of the patient are detailed here. The treatment plan consisted of modified anterior maxillary osteotomy for simultaneous vertical and sagittal augmentation along with orthodontic intervention. The course of surgical-orthodontic treatment and the results are presented. This treatment is to be followed by correction of vertical maxillary excess after completion of growth. This paper concludes that the dentoalveolar component of a skeletal deformity can be handled independent of the craniofacial management.

  19. Prenatal ultrasound and MRI findings of temporal and occipital lobe dysplasia in a twin with achondroplasia.

    Science.gov (United States)

    Pugash, D; Lehman, A M; Langlois, S

    2014-09-01

    Thanatophoric dysplasia, hypochondroplasia and achondroplasia are all caused by FGFR3 (fibroblast growth factor receptor 3) mutations. Neuropathological findings of temporal lobe dysplasia are found in thanatophoric dysplasia, and temporal and occipital lobe abnormalities have been described recently in brain imaging studies of children with hypochondroplasia. We describe twins discordant for achondroplasia, in one of whom the prenatal diagnosis was based on ultrasound and fetal MRI documentation of temporal and occipital lobe abnormalities characteristic of hypochondroplasia, in addition to the finding of short long bones. Despite the intracranial findings suggestive of hypochondroplasia, achondroplasia was confirmed following postnatal clinical and genetic testing. These intracranial abnormalities have not been previously described in a fetus with achondroplasia. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

  20. Sleep-disordered breathing and its management in children with achondroplasia.

    Science.gov (United States)

    Tenconi, Rossana; Khirani, Sonia; Amaddeo, Alessandro; Michot, Caroline; Baujat, Geneviève; Couloigner, Vincent; De Sanctis, Livio; James, Syril; Zerah, Michel; Cormier-Daire, Valérie; Fauroux, Brigitte

    2017-04-01

    Sleep-disordered breathing is a common feature in children with achondroplasia. The aim of our study was to review the poly(somno)graphic (P(S)G) findings and consequent treatments in children with achondroplasia followed in the national reference center for skeletal dysplasia. A retrospective review of the clinical charts and P(S)G of 43 consecutive children (mean age 3.9 ± 3.5 years) with achondroplasia seen over a period of 2 years was performed. Twenty four (59%) children had obstructive sleep apnea (OSA). Thirteen children had an obstructive apnea-hypopnea index (OAHI) achondroplasia. The observation of a reduced prevalence of OSA after (adeno-)tonsillectomy is in favor of this type of surgery when possible. © 2017 Wiley Periodicals, Inc.

  1. Achondroplasia with multiple-suture craniosynostosis: a report of a new case of this rare association.

    Science.gov (United States)

    Bessenyei, Beáta; Nagy, Andrea; Balogh, Erzsébet; Novák, László; Bognár, László; Knegt, Alida C; Oláh, Eva

    2013-10-01

    We report on a female patient with an exceedingly rare combination of achondroplasia and multiple-suture craniosynostosis. Besides the specific features of achondroplasia, synostosis of the metopic, coronal, lambdoid, and squamosal sutures was found. Series of neurosurgical interventions were carried out, principally for acrocephaly and posterior plagiocephaly. The most common achondroplasia mutation, a p.Gly380Arg in the fibroblast growth factor receptor 3 (FGFR3) gene, was detected. Cytogenetic and array CGH analyses, as well as molecular genetic testing of FGFR1, 2, 3 and TWIST1 genes failed to identify any additional genetic alteration. It is suggested that this unusual phenotype is a result of variable expressivity of the common achondroplasia mutation. Copyright © 2013 Wiley Periodicals, Inc.

  2. A common FGFR3 gene mutation is present in achondroplasia but not in hypochondroplasia

    Energy Technology Data Exchange (ETDEWEB)

    Stoilov, I.; Kilpatrick, M.W.; Tsipouras, P. [Univ. of Connecticut Health Center, Farmington, CT (United States)

    1995-01-02

    Achondroplasia is the most common type of genetic dwarfism. It is characterized by disproportionate short stature and other skeletal anomalies resulting from a defect in the maturation of the chondrocytes in the growth plate of the cartilage. Recent studies mapped the achondroplasia gene on chromosome region 4p16.3 and identified a common mutation in the gene encoding the fibroblast growth factor receptor 3 (FGFR3). In an analysis of 19 achondroplasia families from a variety of ethnic backgrounds we confirmed the presence of the G380R mutation in 21 of 23 achondroplasia chromosomes studied. In contrast, the G380R mutation was not found in any of the 8 hypochondroplasia chromosomes studied. Futhermore, linkage studies in a 3-generation family with hypochondroplasia show discordant segregation with markers in the 4p16.3 region suggesting that at least some cases of hypochondroplasia are caused by mutations in a gene other than FGFR3. 27 refs., 2 figs.

  3. Magnetic resonance evaluation of the knee in children and adolescents with achondroplasia

    International Nuclear Information System (INIS)

    Akyol, Yakup; Averill, Lauren W.; Atanda, Alfred; Mackenzie, William G.; Kecskemethy, Heidi H.; Bober, Michael B.

    2015-01-01

    Achondroplasia is the most common form of skeletal dysplasia. Although the radiographic features are well described, MRI features of the knee in achondroplasia have not been reported. To describe common MRI characteristics of the knee joint in symptomatic children and adolescents with achondroplasia. We retrospectively evaluated 10 knee MRI examinations in 8 children and young adults (age range 11-20 years, mean 16.3 years) with achondroplasia. We measured modified Insall-Salvati index, knee flexion angle, anterior cruciate ligament (ACL)-Blumensaat line angle, ACL-tibial angle, posterior cruciate ligament (PCL) angle, intercondylar notch width index, and intercondylar notch depth index. We compared our findings with an age- and gender-matched control group of 20 children (age range 15-18 years; mean 16 years) with normal knee MRIs. All 10 knees in the achondroplasia group had discoid lateral meniscus; 8 meniscal tears were identified. Patella baja was present in half of the study cases. Greater knee flexion and increased ACL-Blumensaat line and PCL angles were seen in all achondroplasia knees. ACL-tibial angle was similar in the study and in the control group. Children with achondroplasia had deeper A-shape femoral notches that extended more anteriorly than those seen in the control group. MRI findings were confirmed in all seven knees with arthroscopic correlation. Discoid lateral meniscus, often with tear, is a consistent feature in knee MRIs of symptomatic children and adolescents with achondroplasia. Other findings include patella baja, knee flexion, deep A-shape intercondylar notch, increased ACL-Blumensaat line angle and taut PCL. (orig.)

  4. Magnetic resonance evaluation of the knee in children and adolescents with achondroplasia.

    Science.gov (United States)

    Akyol, Yakup; Averill, Lauren W; Atanda, Alfred; Kecskemethy, Heidi H; Bober, Michael B; Mackenzie, William G

    2015-06-01

    Achondroplasia is the most common form of skeletal dysplasia. Although the radiographic features are well described, MRI features of the knee in achondroplasia have not been reported. To describe common MRI characteristics of the knee joint in symptomatic children and adolescents with achondroplasia. We retrospectively evaluated 10 knee MRI examinations in 8 children and young adults (age range 11-20 years, mean 16.3 years) with achondroplasia. We measured modified Insall-Salvati index, knee flexion angle, anterior cruciate ligament (ACL)-Blumensaat line angle, ACL-tibial angle, posterior cruciate ligament (PCL) angle, intercondylar notch width index, and intercondylar notch depth index. We compared our findings with an age- and gender-matched control group of 20 children (age range 15-18 years; mean 16 years) with normal knee MRIs. All 10 knees in the achondroplasia group had discoid lateral meniscus; 8 meniscal tears were identified. Patella baja was present in half of the study cases. Greater knee flexion and increased ACL-Blumensaat line and PCL angles were seen in all achondroplasia knees. ACL-tibial angle was similar in the study and in the control group. Children with achondroplasia had deeper A-shape femoral notches that extended more anteriorly than those seen in the control group. MRI findings were confirmed in all seven knees with arthroscopic correlation. Discoid lateral meniscus, often with tear, is a consistent feature in knee MRIs of symptomatic children and adolescents with achondroplasia. Other findings include patella baja, knee flexion, deep A-shape intercondylar notch, increased ACL-Blumensaat line angle and taut PCL.

  5. Magnetic resonance evaluation of the knee in children and adolescents with achondroplasia

    Energy Technology Data Exchange (ETDEWEB)

    Akyol, Yakup; Averill, Lauren W. [Nemours/Alfred I. duPont Hospital for Children, Department of Medical Imaging, Wilmington, DE (United States); Atanda, Alfred; Mackenzie, William G. [Nemours/Alfred I. duPont Hospital for Children, Department of Orthopedics, Wilmington, DE (United States); Kecskemethy, Heidi H. [Nemours/Alfred I. duPont Hospital for Children, Department of Medical Imaging, Wilmington, DE (United States); Nemours/Alfred I. duPont Hospital for Children, Department of Biomedical Research, Wilmington, DE (United States); Bober, Michael B. [Nemours/Alfred I. duPont Hospital for Children, Division of Genetics, Department of Pediatrics, Wilmington, DE (United States)

    2015-06-15

    Achondroplasia is the most common form of skeletal dysplasia. Although the radiographic features are well described, MRI features of the knee in achondroplasia have not been reported. To describe common MRI characteristics of the knee joint in symptomatic children and adolescents with achondroplasia. We retrospectively evaluated 10 knee MRI examinations in 8 children and young adults (age range 11-20 years, mean 16.3 years) with achondroplasia. We measured modified Insall-Salvati index, knee flexion angle, anterior cruciate ligament (ACL)-Blumensaat line angle, ACL-tibial angle, posterior cruciate ligament (PCL) angle, intercondylar notch width index, and intercondylar notch depth index. We compared our findings with an age- and gender-matched control group of 20 children (age range 15-18 years; mean 16 years) with normal knee MRIs. All 10 knees in the achondroplasia group had discoid lateral meniscus; 8 meniscal tears were identified. Patella baja was present in half of the study cases. Greater knee flexion and increased ACL-Blumensaat line and PCL angles were seen in all achondroplasia knees. ACL-tibial angle was similar in the study and in the control group. Children with achondroplasia had deeper A-shape femoral notches that extended more anteriorly than those seen in the control group. MRI findings were confirmed in all seven knees with arthroscopic correlation. Discoid lateral meniscus, often with tear, is a consistent feature in knee MRIs of symptomatic children and adolescents with achondroplasia. Other findings include patella baja, knee flexion, deep A-shape intercondylar notch, increased ACL-Blumensaat line angle and taut PCL. (orig.)

  6. Effect of the G375C and G346E achondroplasia mutations on FGFR3 activation.

    Directory of Open Access Journals (Sweden)

    Lijuan He

    Full Text Available Two mutations in FGFR3, G380R and G375C are known to cause achondroplasia, the most common form of human dwarfism. The G380R mutation accounts for 98% of the achondroplasia cases, and thus has been studied extensively. Here we study the effect of the G375C mutation on the phosphorylation and the cross-linking propensity of full-length FGFR3 in HEK 293 cells, and we compare the results to previously published results for the G380R mutant. We observe identical behavior of the two achondroplasia mutants in these experiments, a finding which supports a direct link between the severity of dwarfism phenotypes and the level and mechanism of FGFR3 over-activation. The mutations do not increase the cross-linking propensity of FGFR3, contrary to previous expectations that the achondroplasia mutations stabilize the FGFR3 dimers. Instead, the phosphorylation efficiency within un-liganded FGFR3 dimers is increased, and this increase is likely the underlying cause for pathogenesis in achondroplasia. We further investigate the G346E mutation, which has been reported to cause achondroplasia in one case. We find that this mutation does not increase FGFR3 phosphorylation and decreases FGFR3 cross-linking propensity, a finding which raises questions whether this mutation is indeed a genetic cause for human dwarfism.

  7. De novo achondroplasia causing four consecutive unsuccessful pregnancies: a case report

    Directory of Open Access Journals (Sweden)

    Igwegbe Anthony

    2012-08-01

    Full Text Available Abstract Introduction The incidence of achondroplasia is very low, and the birth of two or more consecutive babies with achondroplasia to unaffected parents is a rarity. We report a rare case of recurrent achondroplasia in babies of unaffected parents. Case presentation A 29-year-old Nigerian Igbo woman who has had three consecutive dead achondroplastic babies presented at a gestational age of 31 weeks with a two-hour history of drainage of liquor and vaginal bleeding. Neither she nor her husband had features of achondroplasia. Fundal height was compatible with the gestational age. Fetal heart activity was present. An abdominal ultrasound examination showed a viable fetus with short long bones, oligohydramnios, and a fundal placenta with a small retroplacental blood clot. Our patient was stabilized and had an emergency Cesarean section for grade 1 abruptio placentae. A live male baby with Apgar scores of 4 at one minute and 5 at 10 minutes was delivered. The baby had classic features of achondroplasia and died shortly after birth. Conclusions To the best of our knowledge, this is the first reported case of recurrent achondroplasia in siblings of unaffected parents in Nigeria. Management is challenging, and the outcomes of future pregnancies appear bleak. However, proper counseling and follow-up are needed. There is also a need to establish preconception clinics and facilities for prenatal genetic diagnosis and gene therapy in developing countries.

  8. Widening of the femoral proximal diaphysis--metaphysis angle in fetuses with achondroplasia.

    Science.gov (United States)

    Khalil, A; Morales-Roselló, J; Morlando, M; Bhide, A; Papageorghiou, A; Thilaganathan, B

    2014-07-01

    It has recently been reported that fetuses with achondroplasia have a wider than expected femoral proximal diaphysis-metaphysis angle (femoral angle). The aim of this case-control study was to investigate this finding. Cases with confirmed achondroplasia (n = 6), small-for-gestational-age fetuses (n = 70) and a group of normal fetuses (n = 377) were included in this study. The ultrasound image of the femur was examined by two independent experienced observers blinded to the diagnosis, who measured the femoral angle. These values were converted into multiples of the expected median (MoM), after adjustment for gestational age and femur length. Prevalence of various prenatal ultrasound signs of achondroplasia was determined in affected fetuses. Intra- and interobserver agreement of measurement of femoral angle was assessed using 95% limits of agreement and kappa statistics. The femoral angle can be measured accurately by ultrasound, and increases with both increasing gestational age and increasing femur length. The femoral angle-MoM was significantly higher in fetuses with achondroplasia than in the control group (1.36 vs 1.00 MoM, P achondroplasia (83.3%), which was the most consistent finding other than shortening of the long bones. The femoral angle is wider in fetuses with achondroplasia. This new ultrasound sign appears promising as an additional discriminatory marker when clinicians are faced with a case of short long bones in the third trimester. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

  9. Effect of the G375C and G346E achondroplasia mutations on FGFR3 activation.

    Science.gov (United States)

    He, Lijuan; Serrano, Christopher; Niphadkar, Nitish; Shobnam, Nadia; Hristova, Kalina

    2012-01-01

    Two mutations in FGFR3, G380R and G375C are known to cause achondroplasia, the most common form of human dwarfism. The G380R mutation accounts for 98% of the achondroplasia cases, and thus has been studied extensively. Here we study the effect of the G375C mutation on the phosphorylation and the cross-linking propensity of full-length FGFR3 in HEK 293 cells, and we compare the results to previously published results for the G380R mutant. We observe identical behavior of the two achondroplasia mutants in these experiments, a finding which supports a direct link between the severity of dwarfism phenotypes and the level and mechanism of FGFR3 over-activation. The mutations do not increase the cross-linking propensity of FGFR3, contrary to previous expectations that the achondroplasia mutations stabilize the FGFR3 dimers. Instead, the phosphorylation efficiency within un-liganded FGFR3 dimers is increased, and this increase is likely the underlying cause for pathogenesis in achondroplasia. We further investigate the G346E mutation, which has been reported to cause achondroplasia in one case. We find that this mutation does not increase FGFR3 phosphorylation and decreases FGFR3 cross-linking propensity, a finding which raises questions whether this mutation is indeed a genetic cause for human dwarfism.

  10. Concomitant achondroplasia and developmental dysplasia of the hip

    Directory of Open Access Journals (Sweden)

    Tennison L. Malcolm, MD

    2015-12-01

    Full Text Available Achondroplasia (ACH is the most common form of hereditary dwarfism and presents with multiple musculoskeletal anomalies but is not normally associated with premature hip arthritis. Developmental dysplasia of the hip (DDH is a spectrum of disease resulting in shallow acetabular depth and a propensity for chronic femoral subluxation or dislocation; it is among the most common causes of premature arthritis. This case report describes the diagnosis of symptomatic DDH in a patient with ACH and highlights difficulties of primary total hip arthroplasty (THA as a treatment option. Intraoperative radiographic imaging is advised to ensure proper prosthesis placement. Femoral osteotomy may aid visualization, reduction, and avoidance of soft tissue injury. Concomitant ACH and DDH is a challenging problem that can be successfully treated with modified THA.

  11. 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.

  12. [From gene to disease; achondroplasia and other skeletal dysplasias due to an activating mutation in the fibroblast growth factor

    NARCIS (Netherlands)

    Ravenswaaij-Arts, C.M.A. van; Losekoot, M.

    2001-01-01

    Achondroplasia, the most common and best known skeletal dysplasia, is inherited in an autosomal dominant fashion. Like a number of other skeletal dysplasias, among which hypochondroplasia and thanatophoric dysplasia, achondroplasia is caused by mutations in the fibroblast growth factor receptor 3

  13. Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia.

    Science.gov (United States)

    Saint-Laurent, Celine; Garcia, Stephanie; Sarrazy, Vincent; Dumas, Karine; Authier, Florence; Sore, Sophie; Tran, Albert; Gual, Philippe; Gennero, Isabelle; Salles, Jean-Pierre; Gouze, Elvire

    2018-01-01

    Achondroplasia is a rare genetic disease is characterized by abnormal bone development and early obesity. While the bone aspect of the disease has been thoroughly studied, early obesity affecting approximately 50% of them during childhood has been somewhat neglected. It nevertheless represents a major health problem in these patients, and is associated to life-threatening complications including increasing risk of cardiovascular pathologies. We have thus decided to study obesity in patients and to use the mouse model to evaluate if soluble FGFR3 therapy, an innovative treatment approach for achondroplasia, could also impact the development of this significant complication. To achieve this, we have first fully characterized the metabolic deregulations in these patients by conducting a longitudinal retrospective study, in children with achondroplasia Anthropometric, densitometric measures as well as several blood parameters were recorded and compared between three age groups ranging from [0-3], [4-8] and [9-18] years old. Our results show unexpected results with the development of an atypical obesity with preferential fat deposition in the abdomen that is remarkably not associated with classical complications of obesity such as diabetes or hypercholosterolemia. Because it is not associated with diabetes, the atypical obesity has not been studied in the past even though it is recognized as a real problem in these patients. These results were validated in a murine model of achondroplasia (Fgfr3ach/+) where similar visceral adiposity was observed. Unexpected alterations in glucose metabolism were highlighted during high-fat diet. Glucose, insulin or lipid levels remained low, without the development of diabetes. Very interestingly, in achondroplasia mice treated with soluble FGFR3 during the growth period (from D3 to D22), the development of these metabolic deregulations was prevented in adult animals (between 4 and 14 weeks of age). The lean-over-fat tissues ratio was

  14. Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia

    Science.gov (United States)

    Sarrazy, Vincent; Dumas, Karine; Authier, Florence; Sore, Sophie; Tran, Albert; Gual, Philippe; Gennero, Isabelle; Salles, Jean-Pierre; Gouze, Elvire

    2018-01-01

    Background Achondroplasia is a rare genetic disease is characterized by abnormal bone development and early obesity. While the bone aspect of the disease has been thoroughly studied, early obesity affecting approximately 50% of them during childhood has been somewhat neglected. It nevertheless represents a major health problem in these patients, and is associated to life-threatening complications including increasing risk of cardiovascular pathologies. We have thus decided to study obesity in patients and to use the mouse model to evaluate if soluble FGFR3 therapy, an innovative treatment approach for achondroplasia, could also impact the development of this significant complication. Methods and findings To achieve this, we have first fully characterized the metabolic deregulations in these patients by conducting a longitudinal retrospective study, in children with achondroplasia Anthropometric, densitometric measures as well as several blood parameters were recorded and compared between three age groups ranging from [0–3], [4–8] and [9–18] years old. Our results show unexpected results with the development of an atypical obesity with preferential fat deposition in the abdomen that is remarkably not associated with classical complications of obesity such as diabetes or hypercholosterolemia. Because it is not associated with diabetes, the atypical obesity has not been studied in the past even though it is recognized as a real problem in these patients. These results were validated in a murine model of achondroplasia (Fgfr3ach/+) where similar visceral adiposity was observed. Unexpected alterations in glucose metabolism were highlighted during high-fat diet. Glucose, insulin or lipid levels remained low, without the development of diabetes. Very interestingly, in achondroplasia mice treated with soluble FGFR3 during the growth period (from D3 to D22), the development of these metabolic deregulations was prevented in adult animals (between 4 and 14 weeks of age

  15. The Tibial Slope in Patients With Achondroplasia: Its Characterization and Possible Role in Genu Recurvatum Development.

    Science.gov (United States)

    Brooks, Jaysson T; Bernholt, David L; Tran, Kevin V; Ain, Michael C

    2016-06-01

    Genu recurvatum, a posterior resting position of the knee, is a common lower extremity deformity in patients with achondroplasia and has been thought to be secondary to ligamentous laxity. To the best of our knowledge, the role of the tibial slope has not been investigated, and no studies describe the tibial slope in patients with achondroplasia. Our goals were to characterize the tibial slope in children and adults with achondroplasia, explore its possible role in the development of genu recurvatum, and compare the tibial slope in patients with achondroplasia to that in the general population. We reviewed 252 lateral knee radiographs of 130 patients with achondroplasia seen at our clinic from November 2007 through September 2013. Patients were excluded if they had previous lower extremity surgery or radiographs with extreme rotation. We analyzed patient demographics and, on all radiographs, the tibial slope. We then compared the mean tibial slope to norms in the literature. Tibial slopes >90 degrees had an anterior tibial slope and received a positive prefix. Statistical analysis included intraclass and interclass reliability, Pearson correlation coefficient, and the Student t tests (significance, Pachondroplasia than in the general population; however, this difference diminishes as patients' age. An anterior tibial slope may predispose to a more posterior resting knee position, also known as genu recurvatum. Level IV-retrospective case series.

  16. Neurological symptoms, evaluation and treatment in Danish patients with achondroplasia and hypochondroplasia

    DEFF Research Database (Denmark)

    Doherty, Mia Aagaard; Hertel, Niels Thomas; Hove, Hanne Buciek

    2017-01-01

    Aim To investigate the prevalence of neurological symptoms and the types of complications in a cohort of Danish patients with mutation verified achondroplasia and hypochondroplasia and compare the results with previously reported findings. Methods Retrospective descriptive study by chart review...... of patients followed in three outpatients clinics in the period 1997-2014. Forty-eight patients with achondroplasia and a median age of 9,5 years old and 20 patients with hypochondroplasia and a median age of 12 years old were enrolled. Neurological manifestations, epidemiological variables and clinical data...... for referral to an MRI scan or neurosurgery. Conclusion Through investigation of phenotypes and genotypes in patients with achondroplasia and hypochondroplasia we report the frequencies of neurological symptoms, foramen magnum stenosis, spinal cord compression and neurosurgery in Danish patients. Variation...

  17. Limb shortening osteotomy in a patient with achondroplasia and leg length difference after total hip arthroplasty

    Directory of Open Access Journals (Sweden)

    Christian L. Galata

    2013-07-01

    Full Text Available Introduction: Achondroplasia is the most common reason for disproportionate short stature. Normally, orthopedic limb lengthening procedures must be discussed in the course of this genetic disorder and have been successful in numerous achondroplastic patients in the past. In some cases, the disease may lead to leg length differences with need for surgical correction. Case Report: We report a case of achondroplastic dysplastic coxarthrosis with symptomatic leg length difference after bilateral total hip arthroplasty in a 52-year-old female patient, in which a distal femoral shortening osteotomy was successfully performed. Conclusion: Femoral shortening osteotomy is very uncommon in patients with achondroplasia. We conclude, however, that in rare cases it can be indicated and provide the advantage of shorter operation time, less perioperative complications and faster recovery compared to leg lengthening procedures. Keywords: Achondroplasia, dysplastic coxarthrosis, limb shortening, distal femur osteotomy.

  18. Early impairment of somatosensory evoked potentials in very young children with achondroplasia with foramen magnum stenosis.

    Science.gov (United States)

    Fornarino, Stefania; Rossi, Daniela Paola; Severino, Mariasavina; Pistorio, Angela; Allegri, Anna Elsa Maria; Martelli, Simona; Doria Lamba, Laura; Lanteri, Paola

    2017-02-01

    To evaluate the contribution of somatosensory evoked potentials after median nerve (MN-SEPs) and posterior tibial nerve (PTN-SEPs) stimulation in functional assessment of cervical and lumbar spinal stenosis in children with achondroplasia. We reviewed MN-SEPs, PTN-SEPs, and spinal magnetic resonance imaging (MRI) examinations performed in 58 patients with achondroplasia (25 males, 33 females; age range 21d-16y 10mo; mean age 4y 3mo [SD 4y 1mo]). Patients were subdivided into four age categories: achondroplasia, the cortical component of PTN-SEPs is more sensitive than the cortical component and central conduction time of MN-SEPs in detection of cervical spinal cord compression at early ages. © 2016 Mac Keith Press.

  19. Arthroscopic Treatment of Discoid Lateral Meniscus Tears in Children With Achondroplasia.

    Science.gov (United States)

    Atanda, Alfred; Wallace, Maegen; Bober, Michael B; Mackenzie, William

    2016-01-01

    Achondroplasia is the most common form of skeletal dysplasia that presents to the pediatric orthopaedist. More than half of achondroplasia patients are affected with knee pain. It is thought that the majority of this pain may be due to spinal stenosis, hip pathology, or knee malalignment. Discoid menisci can be a source of lateral knee joint pain in skeletally immature patients in general. We present the first case series of patients with achondroplasia who had symptomatic discoid lateral menisci treated with arthroscopic knee surgery. The charts of 6 patients (8 knees) with achondroplasia who underwent arthroscopic knee surgery for symptomatic discoid lateral menisci were collected. History and physical examination data, magnetic resonance imaging findings, and operative reports were reviewed. Meniscal tear configuration and treatment type (meniscectomy vs. repair) were noted. Each patient was found to have a tear of the discoid meniscus. All menisci were treated with saucerization. In addition, meniscal repair was performed in 2 cases, partial meniscectomy in 3 cases, and subtotal meniscectomy in 3 cases. Two patients had bilateral discoid meniscal tears which were treated. Average follow-up was 2.4 years (range, 1 to 4.5 y) and the average pediatric International Knee Documentation Committee (pedi-IKDC) score was 85.3% (range, 75% to 95.4%). At final follow-up, all patients were pain free and able to return to full activities. Discoid meniscus tears may be a source of lateral joint line pain in patients with achondroplasia. These injuries can be successfully treated with arthroscopic surgery in this patient population. Future studies need to be done to determine the exact incidence of discoid menisci in achondroplasia patients and also to determine whether there is a genetic relationship between the 2 conditions. Level IV-case series.

  20. Age-related X-ray feature of the spine in patients with achondroplasia

    International Nuclear Information System (INIS)

    Shevtsov, V.I.; D'yachkova, G.V.; Novikova, O.S.

    1999-01-01

    Age-related X-ray features of the spine in patients with achondroplasia are studied. It gives the time course of changes in the shape of vertebrae, the specific features of apophyseal ossification, provides a quantitative account of the shorter caudal lumbar vertebral arch root distance symptom. The time course of changes in the size of the lumbosacral angle was examined. The findings suggest that there are not only considerable static changes in the spine of patients with achondroplasia, but also significant age-related features of vertebral tissue growth and differentiation [ru

  1. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome.

    Science.gov (United States)

    Wilkin, D J; Szabo, J K; Cameron, R; Henderson, S; Bellus, G A; Mack, M L; Kaitila, I; Loughlin, J; Munnich, A; Sykes, B; Bonaventure, J; Francomano, C A

    1998-01-01

    More than 97% of achondroplasia cases are caused by one of two mutations (G1138A and G1138C) in the fibroblast growth factor receptor 3 (FGFR3) gene, which results in a specific amino acid substitution, G380R. Sporadic cases of achondroplasia have been associated with advanced paternal age, suggesting that these mutations occur preferentially during spermatogenesis. We have determined the parental origin of the achondroplasia mutation in 40 sporadic cases. Three distinct 1-bp polymorphisms were identified in the FGFR3 gene, within close proximity to the achondroplasia mutation site. Ninety-nine families, each with a sporadic case of achondroplasia in a child, were analyzed in this study. In this population, the achondroplasia mutation occurred on the paternal chromosome in all 40 cases in which parental origin was unambiguous. This observation is consistent with the clinical observation of advanced paternal age resulting in new cases of achondroplasia and suggests that factors influencing DNA replication or repair during spermatogenesis, but not during oogenesis, may predispose to the occurrence of the G1138 FGFR3 mutations. PMID:9718331

  2. FGFR3 mutation causes abnormal membranous ossification in achondroplasia.

    Science.gov (United States)

    Di Rocco, Federico; Biosse Duplan, Martin; Heuzé, Yann; Kaci, Nabil; Komla-Ebri, Davide; Munnich, Arnold; Mugniery, Emilie; Benoist-Lasselin, Catherine; Legeai-Mallet, Laurence

    2014-06-01

    FGFR3 gain-of-function mutations lead to both chondrodysplasias and craniosynostoses. Achondroplasia (ACH), the most frequent dwarfism, is due to an FGFR3-activating mutation which results in impaired endochondral ossification. The effects of the mutation on membranous ossification are unknown. Fgfr3(Y367C/+) mice mimicking ACH and craniofacial analysis of patients with ACH and FGFR3-related craniosynostoses provide an opportunity to address this issue. Studying the calvaria and skull base, we observed abnormal cartilage and premature fusion of the synchondroses leading to modifications of foramen magnum shape and size in Fgfr3(Y367C/+) mice, ACH and FGFR3-related craniosynostoses patients. Partial premature fusion of the coronal sutures and non-ossified gaps in frontal bones were also present in Fgfr3(Y367C/+) mice and ACH patients. Our data provide strong support that not only endochondral ossification but also membranous ossification is severely affected in ACH. Demonstration of the impact of FGFR3 mutations on craniofacial development should initiate novel pharmacological and surgical therapeutic approaches.

  3. Rotational profile of the lower extremity in achondroplasia: computed tomographic examination of 25 patients

    Energy Technology Data Exchange (ETDEWEB)

    Song, Hae-Ryong; Suh, Seung-Woo [Korea University Guro Hospital, Department of Orthopaedic Surgery, Rare Diseases Institute, Seoul (Korea); Choonia, Abi-Turab [Laud Clinic, Department of Orthopaedic Surgery, Mumbai (India); Hong, Suk Joo; Cha, In Ho [Korea University Guro Hospital, Department of Radiology, Seoul (Korea); Lee, Seok-Hyun [Dongguk University Ilsan Buddist Hospital, Department of Orthopaedic Surgery, Goyang (Korea); Park, Jong-Tae [Korea University Ansan Hospital, Department of Occupational and Enviornmental Medicine, Ansan (Korea)

    2006-12-15

    To evaluate lower-extremity rotational abnormalities in subjects with achondroplasia using computed tomography (CT) scans. CT scans were performed in 25 subjects with achondroplasia (13 skeletally immature, mean age 8.7 years; 12 skeletally mature, mean age 17.6 years). In a total of 50 bilateral limbs, CT images were used to measure the angles of acetabular anteversion, femoral anteversion, and tibial external torion. Measurement was performed by three examiners and then repeated by one examiner. Inter- and intraobserver agreements were analyzed, and results were compared with previously reported normal values. Mean values for skeletally immature and skeletally mature subjects were 13.6{+-}7.5 and 21.5{+-}6.4 respectively for acetabular anteversion, 27.1{+-}20.8 and 30.5{+-}20.1 for femoral torsion, and 21.6{+-}10.6 and 22.5{+-}10.8 for tibial torsion. Intra- and interobserver agreements were good to excellent. Acetabular anteversion and femoral anteversion in skeletally mature subjects were greater than normal values in previous studies. Both skeletally immature and mature subjects with achondroplasia had decreased tibial torsion compared to normal skeletally immature and mature subjects. Lower-extremity rotational abnormalities in subjects with achondroplasia include decreased tibial external torsion in both skeletally immature and mature subjects, as well as increased femoral and acetabular anteversion in skeletally mature subjects. (orig.)

  4. The effect of height, weight and head circumference on gross motor development in achondroplasia.

    Science.gov (United States)

    Ireland, Penelope Jane; Ware, Robert S; Donaghey, Samantha; McGill, James; Zankl, Andreas; Pacey, Verity; Ault, Jenny; Savarirayan, Ravi; Sillence, David; Thompson, Elizabeth; Townshend, Sharron; Johnston, Leanne M

    2013-02-01

    This study aimed to investigate whether height, weight, head circumference and/or relationships between these factors are associated with gross motor milestone acquisition in children with achondroplasia. Population-based data regarding timing of major gross motor milestones up to 5 years were correlated with height, weight and head circumference at birth and 12 months in 48 children with achondroplasia born in Australia and New Zealand between 2000 and 2009. Although as a group children with achondroplasia showed delayed gross motor skill acquisition, within group differences in height, weight or head circumference did not appear to influence timing of gross motor skills before 5 years. The exception was lie to sit transitioning, which appears likely to occur earlier if the child is taller and heavier at 12 months, and later if the child has significant head-to-body disproportion. This is the first study to investigate the relationship between common musculoskeletal impairments associated with achondroplasia and timing of gross motor achievement. Identification of the musculoskeletal factors that exacerbate delays in transitioning from lying to sitting will assist clinicians to provide more proactive assessment, advice and intervention regarding motor skill acquisition for this population. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  5. Is there a correlation between sleep disordered breathing and foramen magnum stenosis in children with achondroplasia?

    Science.gov (United States)

    White, Klane K; Parnell, Shawn E; Kifle, Yemiserach; Blackledge, Marcella; Bompadre, Viviana

    2016-01-01

    Children with achondroplasia have midface hypoplasia, frontal bossing, spinal stenosis, rhizomelia, and a small foramen magnum. Central sleep apnea, with potential resultant sudden death, is thought to be related to compression of the spinal cord at the cervicomedullary junction in these patients. Screening polysomnography and/or cervical spine MRI are often performed for infants with achondroplasia. Decompressive suboccipital craniectomy has been performed in selected cases. We aim to better delineate the relationship between polysomnography, cervical spine MRI, and indications for surgical decompression in achondroplasia.We retrospectively review electronic medical records of all children with achondroplasia in our IRB-approved skeletal dysplasia registry who had received screening polysomnography and cervical spine MRI examination was performed. We explored correlations of polysomnography, MRI parameters, and need for decompressive surgery. Seventeen patients with both polysomnography and MRI of the cervical spine met inclusion criteria. The average age at time of the sleep study was 2.4 ± 3.6 years. An abnormal apnea-hypopnea index was found in all patients, with central sleep apnea found in 6/17. Five patients (29%) required foramen magnum decompression. We found no statistically significant correlation between central sleep apnea and abnormal MRI findings suggestive of foramen magnum stenosis. Screening polysomnography is an important tool but does not appear to correlate with MRI findings of foramen magnum stenosis. Cord compression, with either associated T2 cord signal abnormality or clinical findings of clonus, was most predictive of subsequent surgical decompression. © 2015 Wiley Periodicals, Inc.

  6. Postnatal soluble FGFR3 therapy rescues achondroplasia symptoms and restores bone growth in mice.

    Science.gov (United States)

    Garcia, Stéphanie; Dirat, Béatrice; Tognacci, Thomas; Rochet, Nathalie; Mouska, Xavier; Bonnafous, Stéphanie; Patouraux, Stéphanie; Tran, Albert; Gual, Philippe; Le Marchand-Brustel, Yannick; Gennero, Isabelle; Gouze, Elvire

    2013-09-18

    Achondroplasia is a rare genetic disease characterized by abnormal bone development, resulting in short stature. It is caused by a single point mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3), which leads to prolonged activation upon ligand binding. To prevent excessive intracellular signaling and rescue the symptoms of achondroplasia, we have developed a recombinant protein therapeutic approach using a soluble form of human FGFR3 (sFGFR3), which acts as a decoy receptor and prevents FGF from binding to mutant FGFR3. sFGFR3 was injected subcutaneously to newborn Fgfr3(ach/+) mice-the mouse model of achondroplasia-twice per week throughout the growth period during 3 weeks. Effective maturation of growth plate chondrocytes was restored in bones of treated mice, with a dose-dependent enhancement of skeletal growth in Fgfr3(ach/+) mice. This resulted in normal stature and a significant decrease in mortality and associated complications, without any evidence of toxicity. These results describe a new approach for restoring bone growth and suggest that sFGFR3 could be a potential therapy for children with achondroplasia and related disorders.

  7. Rotational profile of the lower extremity in achondroplasia: computed tomographic examination of 25 patients

    International Nuclear Information System (INIS)

    Song, Hae-Ryong; Suh, Seung-Woo; Choonia, Abi-Turab; Hong, Suk Joo; Cha, In Ho; Lee, Seok-Hyun; Park, Jong-Tae

    2006-01-01

    To evaluate lower-extremity rotational abnormalities in subjects with achondroplasia using computed tomography (CT) scans. CT scans were performed in 25 subjects with achondroplasia (13 skeletally immature, mean age 8.7 years; 12 skeletally mature, mean age 17.6 years). In a total of 50 bilateral limbs, CT images were used to measure the angles of acetabular anteversion, femoral anteversion, and tibial external torion. Measurement was performed by three examiners and then repeated by one examiner. Inter- and intraobserver agreements were analyzed, and results were compared with previously reported normal values. Mean values for skeletally immature and skeletally mature subjects were 13.6±7.5 and 21.5±6.4 respectively for acetabular anteversion, 27.1±20.8 and 30.5±20.1 for femoral torsion, and 21.6±10.6 and 22.5±10.8 for tibial torsion. Intra- and interobserver agreements were good to excellent. Acetabular anteversion and femoral anteversion in skeletally mature subjects were greater than normal values in previous studies. Both skeletally immature and mature subjects with achondroplasia had decreased tibial torsion compared to normal skeletally immature and mature subjects. Lower-extremity rotational abnormalities in subjects with achondroplasia include decreased tibial external torsion in both skeletally immature and mature subjects, as well as increased femoral and acetabular anteversion in skeletally mature subjects. (orig.)

  8. Roentgenodiagnostics of soft tissue condition in achondroplasia cases in limb lengthening after Ilizarov

    International Nuclear Information System (INIS)

    D'yachkova, G.V.

    1995-01-01

    Muscles and subcutaneous cellular tissue of upper and lower limbs have been studied in 14 patients with achondroplasia treated after Ilizarov in various periods of lengthening employing contrast roentgenography. The technique applied has allowed to reveal anatomic and topographic features of muscles and subcutaneous cellular tissue in achodroplasia cases and observe changes of morphological parameters in different stages of elongation. 8 refs.; 8 figs

  9. Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele

    NARCIS (Netherlands)

    Rump, P; Letteboer, TGW; Gille, JJP; Torringa, MJL; Baerts, W; van Gestel, JPJ; Verheij, JBGM; van Essen, AJ

    2006-01-01

    We describe a unique case of achondroplasia with associated complications, including severe respiratory problems. Molecular analysis of the fibroblast growth factor receptor type 3 (FGFR3) gene in this patient showed the common p.G380R mutation and a second novel p.L377R Mutation. An allele-specific

  10. Mild achondroplasia/hypochondroplasia with acanthosis nigricans, normal development, and a p.Ser348Cys FGFR3 mutation.

    Science.gov (United States)

    Couser, Natario L; Pande, Chetna K; Turcott, Christie M; Spector, Elaine B; Aylsworth, Arthur S; Powell, Cynthia M

    2017-04-01

    Pathogenic allelic variants in the fibroblast growth factor receptor 3 (FGFR3) gene have been associated with a number of phenotypes including achondroplasia, hypochondroplasia, thanatophoric dysplasia, Crouzon syndrome with acanthosis nigricans (Crouzonodermoskeletal syndrome), and SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans). Crouzon syndrome with acanthosis nigricans is caused by the pathogenic variant c.1172C>A (p.Ala391Glu) in the FGFR3 gene. The p.Lys650Thr pathogenic variant in FGFR3 has been linked to acanthosis nigricans without significant craniofacial or skeletal abnormalities. Recently, an infant with achondroplasia and a novel p.Ser348Cys FGFR3 mutation was reported. We describe the clinical history of an 8-year-old child with a skeletal dysplasia in the achondroplasia-hypochondroplasia spectrum, acanthosis nigricans, typical development, and the recently described p.Ser348Cys FGFR3 mutation. © 2017 Wiley Periodicals, Inc.

  11. Physeal growth arrest after tibial lengthening in achondroplasia: 23 children followed to skeletal maturity.

    Science.gov (United States)

    Song, Sang-Heon; Agashe, Mandar Vikas; Huh, Young-Jae; Hwang, Soon-Young; Song, Hae-Ryong

    2012-06-01

    Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with achondroplasia. We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who underwent bilateral tibial lengthening before skeletal maturity (lengthening group L) and 12 achondroplasia patients of similar height and age who did not undergo tibial lengthening (control group C). The mean amount of lengthening of tibia in group L was 9.2 cm (lengthening percentage: 60%) and the mean age at the time of lengthening was 8.2 years. The mean duration of follow-up was 9.8 years. Skeletal maturity (fusion of physis) occurred at 15.2 years in group L and at 16.0 years in group C. The actual length of tibia (without distraction) at skeletal maturity was 238 mm in group L and 277 mm in group C (p = 0.03). The mean growth rates showed a decrease in group L relative to group C from about 2 years after surgery. Physeal closure was most pronounced on the anterolateral proximal tibial physis, with relative preservation of the distal physis. Our findings indicate that physeal growth rate can be disturbed after tibial lengthening in achondroplasia, and a close watch should be kept for such an occurrence-especially when lengthening of more than 50% is attempted.

  12. Sagittal spinopelvic parameters in children with achondroplasia: identification of 2 distinct groups.

    Science.gov (United States)

    Karikari, Isaac O; Mehta, Ankit I; Solakoglu, Can; Bagley, Carlos A; Ain, Michael C; Gottfried, Oren N

    2012-07-01

    Spinopelvic parameters in children with achondroplasia have not been described. Because they observed a unique sagittal spinopelvic phenotype in some achondroplastic children with very horizontal sacrums, the authors sought to quantify the spinopelvic parameters in a pediatric patient population. A retrospective review was performed to identify all children (age range 1 month-10 years) with a diagnosis of achondroplasia between 2004 and 2009. Clinical and radiographic data were analyzed for age, sex, lumbar lordosis (LL), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI). Differences among these variables were analyzed using a 2-tailed, unpaired Student t-test. Forty children, 23 males and 17 females, with achondroplasia were identified during the study period. The mean age was 2.6 years. Two groups of patients were identified based on PT (that is, negative or positive tilt and horizontal or not horizontal sacrum). A negative PT was identified in all children with an extremely horizontal sacrum. Seventeen children had a negative PT (mean -16.6°), and the mean parameters in this group were 65.4° for LL, 31.7° for TLK, 18.5° for TK, 43.3° for SS, and 26.4° for PI. Twenty-three children had a positive PT (mean 17.9°), and the mean parameters in this group were 53.4° for LL, 41.5° for TLK, 9.6° for TK, 30.8° for SS, and 43.8° for PI. A statistically significant difference was observed for LL (p = 0.01), TLK (p = 0.05), SS (p = 0.006), PT (p = 0.006), and PI (0.0002). Spinopelvic parameters in achondroplasia are potentially dichotomous. The future implications of this observation are not known and will need to be explored in future long-term studies that follow pediatric patients with achondroplasia through adulthood.

  13. Low bone mineral density in achondroplasia and hypochondroplasia.

    Science.gov (United States)

    Matsushita, Masaki; Kitoh, Hiroshi; Mishima, Kenichi; Kadono, Izumi; Sugiura, Hiroshi; Hasegawa, Sachi; Nishida, Yoshihiro; Ishiguro, Naoki

    2016-08-01

    Achondroplasia (ACH) and hypochondroplasia (HCH) are the most common form of short-limb skeletal dysplasias caused by activated fibroblast growth factor receptor 3 (FGFR3) signaling. Although decreased bone mass was reported in gain-of-function mutation in Fgfr3 mice, both disorders have never been described as osteoporotic. In the present study, we evaluated bone mineral density (BMD) in ACH and HCH patients. We measured spinal BMD (L1-L4) in 18 ACH and four HCH patients with an average age of 19.8 ± 7.5 years (range, 10-33 years). BMD Z-score in each individual was calculated for normalizing age and gender. Correlation between body mass index (BMI) and BMD was analyzed. Moreover, BMD and Z-score were compared between ACH patients and HCH patients. The average BMD of ACH/HCH patients was 0.805 ± 0.141 g/cm(2) (range, 0.554-1.056 g/cm(2) ), resulting in an average Z-score of -1.1 ± 0.8 (range, -2.4 to 0.6) of the standard value. A slightly positive correlation was observed between BMI and BMD (r = 0.45; P = 0.13). There was no significant difference in BMD and Z-score between ACH and HCH patients. Spinal BMD was reduced in ACH/HCH patients, and was mildly correlated with individual BMI. We should carefully monitor BMD and examine osteoporosis-related symptoms in adolescent and adult ACH/HCH patients. © 2016 Japan Pediatric Society. © 2015 Japan Pediatric Society.

  14. C-Type Natriuretic Peptide Analog as Therapy for Achondroplasia.

    Science.gov (United States)

    Legeai-Mallet, Laurence

    2016-01-01

    Fibroblast growth factor receptor 3 (FGFR3) is an important regulator of bone formation. Gain-of-function mutations in the FGFR3 gene result in chondrodysplasias which include achondroplasia (ACH), the most common form of dwarfism, in which skull, appendicular and axial skeletons are affected. The skeletal phenotype of patients with ACH showed defective proliferation and differentiation of the chondrocytes in the growth plate cartilage. Both endochondral and membranous ossification processes are disrupted during development. At cellular level, Fgfr3 mutations induce increased phosphorylation of the tyrosine kinase receptor FGFR3, which correlate with an enhanced activation of its downstream signaling pathways. Potential therapeutic strategies have emerged for ACH. Several preclinical studies have been conducted such as the C-type natriuretic peptide (CNP) analog (BMN111), intermittent parathyroid hormone injections, soluble FGFR3 therapy, and meclozine and statin treatments. Among the putative targets to antagonize FGFR3 signaling, CNP (or BMN111) is one of the most promising strategies. BMN111 acts as a key regulator of longitudinal bone growth by downregulating the mitogen-activated protein kinase pathway, which is activated as a result of a FGFR3 gain-of-function mutation. Preclinical studies showed that BMN111 treatment led to a large improvement in skeletal parameters in Fgfr3Y367C/+ mice mimicking ACH. In 2014, a clinical trial (phase 2) of BMN111 in pediatric patients with ACH has started. This first clinical trial marks the first big step towards real treatment for these patients. © 2016 S. Karger AG, Basel.

  15. A height-for-age growth reference for children with achondroplasia: Expanded applications and comparison with original reference data.

    Science.gov (United States)

    Hoover-Fong, Julie; McGready, John; Schulze, Kerry; Alade, Adekemi Yewande; Scott, Charles I

    2017-05-01

    The height-for-age (HA) reference currently used for children with achondroplasia is not adaptable for electronic records or calculation of HA Z-scores. We report new HA curves and tables of mean and standard deviation (SD) HA, for calculating Z-scores, from birth-16 years in achondroplasia. Mixed longitudinal data were abstracted from medical records of achondroplasia patients from a single clinical practice (CIS, 1967-2004). Gender-specific height percentiles (5, 25, 50, 75, 95th) were estimated across the age continuum, using a 2 month window per time point smoothed by a quadratic smoothing algorithm. HA curves were constructed for 0-36 months and 2-16 years to optimize resolution for younger children. Mean monthly height (SD) was tabulated. These novel HA curves were compared to reference data currently in use for children with achondroplasia. 293 subjects (162 male/131 female) contributed 1,005 and 932 height measures, with greater data paucity with age. Mean HA tracked with original achondroplasia norms, particularly through mid-childhood (2-9 years), but with no evidence of a pubertal growth spurt. Standard deviation of height at each month interval increased from birth through 16 years. Birth length was lower in achondroplasia than average stature and, as expected, height deficits increased with age. A new HA reference is available for longitudinal growth assessment in achondroplasia, taking advantage of statistical modeling techniques and allowing for Z-score calculations. This is an important contribution to clinical care and research endeavors for the achondroplasia population. © 2017 Wiley Periodicals, Inc.

  16. Low Prevalence of Anterior and Posterior Cruciate Ligament Injuries in Patients With Achondroplasia.

    Science.gov (United States)

    Brooks, Jaysson T; Ramji, Alim F; Lyapustina, Tatyana A; Yost, Mary T; Ain, Michael C

    2017-01-01

    Anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injuries and their subsequent reconstructions are common in the general population, but there has been no research regarding ACL or PCL injuries in patients with achondroplasia, the most common skeletal dysplasia. Our goals were to (1) evaluate the prevalence of ACL and PCL injuries in adolescents and adults with achondroplasia, (2) compare this prevalence with that reported for the general population, (3) determine how many patients with ACL or PCL injuries underwent ligament reconstruction as treatment, and (4) determine patient activity levels as they relate to the rate of ACL/PCL injuries and reconstructions. We reviewed medical records of 430 patients with achondroplasia seen in the senior author's clinic from 2002 through 2014. Demographic data were reviewed, as well as any documentation of ACL or PCL injury or reconstruction. We called all 430 patients by telephone, and 148 agreed to participate in our survey, whereas 1 declined. We asked these patients about their history of ACL or PCL injury or reconstruction, as well as current and past physical activity levels. No ACL or PCL injuries were found on chart review. One patient reached by telephone reported an ACL injury that did not require reconstruction. This yielded a theoretical prevalence of 3/430 (0.7%). Of the 148 patients surveyed, 43 (29%) reported low physical activity, 75 (51%) reported moderate physical activity, and 26 (17%) reported high physical activity. There was no significant difference in the rate of ACL injury when stratified by physical activity level (P=0.102). ACL and PCL injuries and reconstructions are extremely rare in patients with achondroplasia, which cannot be completely ascribed to a low level of physical activity. One possible explanation is that patients with achondroplasia, on an average, have a more anterior tibial slope compared with those without achondroplasia, which decreases the force generated

  17. Psychosocial profiles of children with achondroplasia in terms of their short stature-related stress: a nationwide survey in Japan.

    Science.gov (United States)

    Nishimura, Naoko; Hanaki, Keiichi

    2014-11-01

    To assess psychosocial profiles of children with achondroplasia using a nationwide survey. Achondroplasia, showing short stature and disproportionately short limbs, causes physical inconvenience such as difficulty in reaching high objects. It is, however, still controversial whether the condition is associated with psychological problems, especially in childhood. A cross-sectional descriptive design was employed. To evaluate psychosocial profiles and adaptation processes in children with achondroplasia, we developed an inventory of scales based on the psychological stress model of which conceptual framework was comprised of stressor, coping process, coping resource and adaptation outcome domains. Participants were recruited nationwide through the largest advocacy support group for achondroplasia in Japan. Of the 130 group members, 73 X-ray-diagnosed patients, aged 8-18 years, completed the inventory of questionnaires to be analysed. As for the stressor domain, patients experienced short stature-related unpleasant experiences more frequently (z-score: +1·3 in average, +3·9 in physical inconvenience). Nevertheless, these experiences had little effect on the coping process (threat appraisal: -0·2, control appraisal: +0·1) and the adaptation outcome (stress response: +0·3, self-concept: 0·0). Interestingly, self-efficacy in the coping resource domain was noticeably increased (+3·1) and was strongly correlated with most variables in the coping process and in adaptation outcome domains. Although the children with achondroplasia experienced more short stature-related stressors, there was no evidence of any psychosocial maladaptation. This finding suggests that coping process as well as coping resources such as self-efficacy could be important targets for promoting psychological adjustment in children with achondroplasia. To help children with achondroplasia adapt socially, nurses and other healthcare providers should routinely assess their psychological adaptation

  18. Deceleration in maturation of bone during adolescent age in achondroplasia - a retrospective study using RUS scoring system

    International Nuclear Information System (INIS)

    Lee, Suk-Ha; Modi, Hitesh N.; Suh, Seung Woo; Song, Hae-Ryong; Hazra, Sunit; Modi, Chetna

    2009-01-01

    Knowledge of bone age in achondroplasia is required for the prediction of adult height, timings of limb lengthening, and epiphysiodesis procedures. The purpose of this investigation was to determine the differences in skeletal age in achondroplasia and a control population with the Tanner-Whitehouse 3 method using the RUS score and to determine the right age for the interventional procedure for limb lengthening procedure or deformity correction in these patients. Left hand radiographs of 34 patients (age range, 5-18 years) with achondroplasia were evaluated for skeletal age using the RUS scoring system, which were compared with the left hand radiographs of 41 patients (age range, 5-18 years) without achondroplasia measuring skeletal age. The difference in chronological age and RUS bone age were evaluated statistically according to gender and age group. In the achondroplasia group, chronological age were 10.5±4.3 years for males and 10.1±3.6 years for females and RUS bone age were 9.2±4.0 years for males and 8.9±3.4 years for females, which showed statistically significantly difference (males p=0.0003 and females p 10 years in the study group, while 0.1±1.1 for 10 years in the control group, which also showed >statistically significant difference ( 10 years p 10 years in achondroplasia patients compared to nonachondroplasia patients. We recommend the use of the Tanner-Whitehouse 3 method especially the radius, ulna, short bone score to measure the skeletal age and to wait for a longer time before interventional procedures in achondroplasia patients. (orig.)

  19. Myxoedema in a patient with achondroplasia in rural area of Guatemala.

    Science.gov (United States)

    Juarez, Michel; Rohloff, Peter

    2017-03-09

    A 43-year-old indigenous Guatemalan woman with achondroplasia presented to our clinic with chronic fatigue and generalised oedema. She had limited contact with the formal healthcare system. However, 1 year prior, she had sought medical evaluation from a private physician. Her symptoms had been attributed to a combination of heart failure and physical disability due to the musculoskeletal complications of her achondroplasia. She was lost to follow-up due to inability to pay for further testing or treatment. On initial laboratory evaluation in our clinic, she was found to have a thyrotropin level greater than assay. With initiation of oral levothyroxine supplementation, her dyspnoea and oedema completely resolved. The case illustrates how indigenous patients in rural Guatemala experience many barriers to accessing high-quality medical care. As a result, presentations of common illnesses are often very advanced and definitive diagnoses and treatments are frequently delayed. 2017 BMJ Publishing Group Ltd.

  20. Intraoperative computed tomography for cervicomedullary decompression of foramen magnum stenosis in achondroplasia: two case reports.

    Science.gov (United States)

    Arishima, Hidetaka; Tsunetoshi, Kenzo; Kodera, Toshiaki; Kitai, Ryuhei; Takeuchi, Hiroaki; Kikuta, Ken-Ichiro

    2013-01-01

    The authors report two cases of cervicomedullary decompression of foramen magnum (FM) stenosis in children with achondroplasia using intraoperative computed tomography (iCT). A 14-month-old girl with myelopathy and retarded motor development, and a 10-year-old girl who had already undergone incomplete FM decompression was presented with myelopathy. Both patients underwent decompressive sub-occipitalcraniectomy and C1 laminectomy without duraplasty using iCT. It clearly showed the extent of FM decompression during surgery, which finally enabled sufficient decompression. After the operation, their myelopathy improved. We think that iCT can provide useful information and guidance for sufficient decompression for FM stenosis in children with achondroplasia.

  1. Alternative technique in atypical spinal decompression: the use of the ultrasonic scalpel in paediatric achondroplasia

    Science.gov (United States)

    Woodacre, Timothy; Sewell, Matthew; Clarke, Andrew J; Hutton, Mike

    2016-01-01

    Spinal stenosis can be a very disabling condition. Surgical decompression carries a risk of dural tear and neural injury, which is increased in patients with severe stenosis or an atypical anatomy. We present an unusual case of symptomatic stenosis secondary to achondroplasia presenting in a paediatric patient, and highlight a new surgical technique used to minimise the risk of dural and neural injury during decompression. PMID:27288205

  2. Achondroplasia manifesting as enchondromatosis and ossification of the spinal ligaments: a case report

    Directory of Open Access Journals (Sweden)

    Al Kaissi Ali

    2008-08-01

    Full Text Available Abstract Introduction A girl presented with achondroplasia manifested as mild knee pain associated with stiffness of her back. A skeletal survey showed enchondroma-like metaphyseal dysplasia and ossification of the spinal ligaments. Magnetic resonance imaging of the spine further clarified the pathological composites. Case presentation A 7-year-old girl presented with the classical phenotypic features of achondroplasia. Radiographic documentation showed the co-existence of metaphyseal enchondromatosis and development of spinal bony ankylosis. Magnetic resonance imaging showed extensive ossification of the anterior and posterior spinal ligaments. Additional features revealed by magnetic resonance imaging included calcification of the peripheral vertebral bodies associated with anterior end-plate irregularities. Conclusion Enchondromas are metabolically active and may continue to grow and evolve throughout the patient's lifetime; thus, progressive calcification over a period of years is not unusual. Ossification of the spinal ligaments has a specific site of predilection and often occurs in combination with senile ankylosing vertebral hyperostosis. Nevertheless, ossification of the spinal ligaments has been encountered in children with syndromic malformation complex. It is a multifactorial disease in which complex genetic and environmental factors interact, potentially leading to chronic pressure on the spinal cord and nerve roots with subsequent development of myeloradiculopathy. Our patient presented with a combination of achondroplasia, enchondroma-like metaphyseal dysplasia and calcification of the spinal ligaments. We suggest that the development of heterotopic bone formation along the spinal ligaments had occurred through an abnormal ossified enchondral mechanism. We postulate that ossification of the spinal ligaments and metaphyseal enchondromatous changes are related to each other and represent impaired terminal differentiation of

  3. Lung function, diagnosis, and treatment of sleep-disordered breathing in children with achondroplasia.

    Science.gov (United States)

    Julliand, Sébastien; Boulé, Michèle; Baujat, Geneviève; Ramirez, Adriana; Couloigner, Vincent; Beydon, Nicole; Zerah, Michel; di Rocco, Federico; Lemerrer, Martine; Cormier-Daire, Valérie; Fauroux, Brigitte

    2012-08-01

    Children with achondroplasia are at risk of sleep-disordered breathing. The aim of the study was to evaluate lung function and sleep-disordered breathing in children with achondroplasia. An interview, clinical examination, lung function tests with blood gases, and a polygraphic sleep study were obtained as part of routine annual evaluation in consecutive children with achondroplasia. We included 30 children (median age 3.0 years, range: 0.4-17.1) over a period of 21 months. Habitual snoring and witnessed apneas were observed in 77% and 33% of the patients, respectively. Prior to the sleep study, 10/29 (34%) patients had undergone upper airway surgery and 5/29 (17%) craniocervical decompression operation. Arterial blood gases were abnormal in two (7%) patients. Sleep findings were abnormal in 28/30 (93%) patients. Eleven (37%) patients had an apnea index≥1 event/hr and 26 (87%) had an apnea-hypopnea index≥5 events/hr. The ≥3% desaturation index was >5/hr in 22 (73%) patients. Sixteen (53%) patients had a minimal pulse oximetry50 mmHg during sleep. As a consequence, the following therapeutic interventions were performed: upper airway surgery in four patients and noninvasive positive pressure ventilation (NPPV) in five other patients, resulting in an improvement in sleep studies in all nine patients. Systematic sleep studies are recommended in children with achondroplasia because of the high prevalence of sleep-disordered breathing. Upper airway surgery and NPPV are effective treatments of sleep-disordered breathing. Copyright © 2012 Wiley Periodicals, Inc.

  4. Best practices in the evaluation and treatment of foramen magnum stenosis in achondroplasia during infancy.

    Science.gov (United States)

    White, Klane K; Bompadre, Viviana; Goldberg, Michael J; Bober, Michael B; Campbell, Jeffrey W; Cho, Tae-Joon; Hoover-Fong, Julie; Mackenzie, William; Parnell, Shawn E; Raggio, Cathleen; Rapoport, David M; Spencer, Samantha A; Savarirayan, Ravi

    2016-01-01

    Achondroplasia is the most common inherited disorder of bone growth (skeletal dysplasia). Despite this fact, consistent and evidence-based management approaches to recognized, life-threatening complications, such as foramen magnum stenosis, are lacking. This study aims to outline best practice, based on evidence and expert consensus, regarding the diagnosis, assessment, and management of foramen magnum stenosis in achondroplasia during infancy. A panel of 11 multidisciplinary international experts on skeletal dysplasia was invited to participate in a Delphi process. They were: 1) presented with a list of 26 indications and a thorough literature review, 2) given the opportunity to anonymously rate the indications and discuss in face to face discussion; 3) edit the list and rate it in a second round. Those indications with more than 80% agreement were considered as consensual. After two rounds of rating and a face-to-face meeting, consensus was reached to support 22 recommendations for the evaluation and treatment of foramen magnum stenosis in infants with achondroplasia. These recommendations include indications for surgical decompression, ventriculomegaly, and hydrocephalus, sleep-disordered breathing, physical exams and the use of polysomnography and imaging in this condition. We present a consensus-based best practice guidelines consisting of 22 recommendations. It is hoped that these guidelines will lead to more uniform and structured evaluation, standardizing care pathways, and improving mortality and morbidity outcomes for this cohort. © 2015 Wiley Periodicals, Inc.

  5. The sagging rope sign in achondroplasia - different from Perthes' disease

    Energy Technology Data Exchange (ETDEWEB)

    Shingade, Viraj U. [Korea University, Department of Paediatric Orthopaedics, College of Medicine, Guro Hospital, Seoul (Korea); Song, Hae-Ryong [Korea University, Department of Paediatric Orthopaedic Surgery, College of Medicine, Guro Hospital, Seoul (Korea); Lee, Seok-Hyun; Suh, Seung-Woo [Korea University, Department of Orthopaedic Surgery, College of Medicine, Guro Hospital, Seoul (Korea); Oh, Chang-Wug [Kyungpook National University Hospital, Department of Orthopaedic Surgery, Daegu (Korea); Hong, Jun-Seok [Ansan Hospital, Department of Orthopaedic Surgery, Korea University, Ansan, Gyeonggi do (Korea)

    2006-12-15

    The sagging rope sign is a radio-opaque line, seen on radiographs of the hips, with Perthes' disease. The main purpose of this study was to determine the incidence, cause and importance of this sign in achondroplasia, and to reveal how it differs from in Perthes' disease. Serial radiograms, along with 2-dimensional and 3-dimensional CT images were studied in 42 achondroplasic patients. Forty-two achondroplasic patients, reported at our institute (for routine outpatient consultation, spine surgeries, deformity corrections, limb-lengthening procedures) were included in this study. There were 26 males and 16 females. The sign was observed bilaterally, in all patients. Evaluation of CT images revealed spherical heads, with presence of circumferential overhang in all hips. This circumferential overhang, seen on 3-D CT scan, corresponded to the sagging rope sign on radiographs. Presence of the sagging rope sign in bilateral hips is a characteristic feature of achondroplasia. It usually appears before epiphyseal closure. Its cause, incidence, and nature differ from Perthes' disease, and its presence does not carry a bad prognosis in achondroplasia. (orig.)

  6. [Quality of life in children, adolescents, and young adults with achondroplasia].

    Science.gov (United States)

    Rohenkohl, A C; Bullinger, M; Quitmann, J

    2015-03-01

    Compared to research on short-statured adults, quality of life (QoL) of children has been rarely studied. One reason for this might be the lack of appropriate disease-specific questionnaires. The aim of this study was to analyse the quality of life in a sample of short-statured children with achondroplasia, using generic and disease-specific instruments. In addition, a comparison of patient and population norms is presented. The sample included children (8-28 years) with achondroplasia and parents of participating children (8-17 years). Quality of life was analyzed with the KIDSCREEN, the DISABKIDS and the disease-specific Quality of Life in Short Stature Youth (QoLISSY) questionnaire. In addition group differences according to clinical and sociodemographic data were analyzed within the sample and compared to available KIDSCREEN representative population data. The physical QoL was rated poorly in this sample of short-statured patients, while the emotional QoL was rated more favorably. Compared to the KIDSCREEN population norm, parents of children with achondroplasia rate the QoL lower. The QoLISSY questionnaire is a reliable tool to assess the subjective wellbeing of patients with skeletal dysplasia. The instrument can now be used clinically as a screening for patient wellbeing, as an outcome criterion in clinical research and as a psychosocial indicator in orthopedic cohort studies.

  7. Long-term follow-up of a patient with achondroplasia treated with an orthodontic approach.

    Science.gov (United States)

    Mori, Hiroyo; Matsumoto, Kazuma; Kawai, Nobuhiko; Izawa, Takashi; Horiuchi, Shinya; Tanaka, Eiji

    2017-04-01

    We successfully treated a patient with achondroplasia with conventional orthodontic techniques. It was followed by long-term retention. The patient, a 12-year-old boy, had chief complaints of occlusal disturbance and mandibular protrusion. He had been diagnosed with achondroplasia and had growth hormone treatment in his early teenage years. His facial profile was concave with a bulging forehead and a retrognathic maxilla. It was characterized by a skeletal Class III jaw-base relationship with a retropositioned maxilla. At the age of 12 years 9 months, maxillary protraction was initiated with a reverse headgear; for 2 years 6 months, the maxillomandibular growth was controlled. After the growth spurt, at the age of 15 years 6 months, leveling and alignment of both dental arches were started with preadjusted edgewise appliances. After 83 months of multibracket treatment, an acceptable occlusion with a Class I molar relationship and an adequate interincisal relationship was achieved, despite the simultaneous marked vertical growth of the mandible. The resultant occlusion was stable during a 6-year retention period, although considerable forward-downward mandibular growth was observed. Conclusively, our results indicated the necessity of long-term observation in this patient with achondroplasia, especially because of the persistent mandibular growth. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  8. Physical basis behind achondroplasia, the most common form of human dwarfism.

    Science.gov (United States)

    He, Lijuan; Horton, William; Hristova, Kalina

    2010-09-24

    Fibroblast growth factor receptor 3 (FGFR3) is a receptor tyrosine kinase that plays an important role in long bone development. The G380R mutation in FGFR3 transmembrane domain is known as the genetic cause for achondroplasia, the most common form of human dwarfism. Despite many studies, there is no consensus about the exact mechanism underlying the pathology. To gain further understanding into the physical basis behind the disorder, here we measure the activation of wild-type and mutant FGFR3 in mammalian cells using Western blots, and we analyze the activation within the frame of a physical-chemical model describing dimerization, ligand binding, and phosphorylation probabilities within the dimers. The data analysis presented here suggests that the mutation does not increase FGFR3 dimerization, as proposed previously. Instead, FGFR3 activity in achondroplasia is increased due to increased probability for phosphorylation of the unliganded mutant dimers. This finding has implications for the design of targeted molecular treatments for achondroplasia.

  9. Association of achondroplasia with Down syndrome: difficulty in prenatal diagnosis by sonographic and 3-D helical computed tomographic analyses.

    Science.gov (United States)

    Kaga, Akimune; Murotsuki, Jun; Kamimura, Miki; Kimura, Masato; Saito-Hakoda, Akiko; Kanno, Junko; Hoshi, Kazuhiko; Kure, Shigeo; Fujiwara, Ikuma

    2015-05-01

    Achondroplasia and Down syndrome are relatively common conditions individually. But co-occurrence of both conditions in the same patient is rare and there have been no reports of fetal analysis of this condition by prenatal sonographic and three-dimensional (3-D) helical computed tomography (CT). Prenatal sonographic findings seen in persons with Down syndrome, such as a thickened nuchal fold, cardiac defects, and echogenic bowel were not found in the patient. A prenatal 3-D helical CT revealed a large head with frontal bossing, metaphyseal flaring of the long bones, and small iliac wings, which suggested achondroplasia. In a case with combination of achondroplasia and Down syndrome, it may be difficult to diagnose the co-occurrence prenatally without typical markers of Down syndrome. © 2014 Japanese Teratology Society.

  10. Deceleration in maturation of bone during adolescent age in achondroplasia - a retrospective study using RUS scoring system

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Suk-Ha [Konkuk University Hospital, Department of Orthopedics, Seoul (Korea); Modi, Hitesh N.; Suh, Seung Woo [Korea University Guro Hospital, Scoliosis Research Institute, Department of Orthopedics, Seoul (Korea); Song, Hae-Ryong; Hazra, Sunit; Modi, Chetna [Korea University Guro Hospital, Rare Disease Institute, Department of Orthopedics, Seoul (Korea)

    2009-02-15

    Knowledge of bone age in achondroplasia is required for the prediction of adult height, timings of limb lengthening, and epiphysiodesis procedures. The purpose of this investigation was to determine the differences in skeletal age in achondroplasia and a control population with the Tanner-Whitehouse 3 method using the RUS score and to determine the right age for the interventional procedure for limb lengthening procedure or deformity correction in these patients. Left hand radiographs of 34 patients (age range, 5-18 years) with achondroplasia were evaluated for skeletal age using the RUS scoring system, which were compared with the left hand radiographs of 41 patients (age range, 5-18 years) without achondroplasia measuring skeletal age. The difference in chronological age and RUS bone age were evaluated statistically according to gender and age group. In the achondroplasia group, chronological age were 10.5{+-}4.3 years for males and 10.1{+-}3.6 years for females and RUS bone age were 9.2{+-}4.0 years for males and 8.9{+-}3.4 years for females, which showed statistically significantly difference (males p=0.0003 and females p < 0.0001), while in the control group, chronological age were 11.1{+-}2.9 years for males and 10.7{+-}3.4 years for females and RUS bone age were 11.2{+-}3.4 years for males and 10.7{+-}3.3 years for females, which did not show statistically significantly difference (males p=0.54 and females p=0.76). Our finding suggested a delay of 1.4 years for males and 1.2 years for females in the maturation of bone in achondroplasia patients. Difference between chronological age and RUS bone age was 0.9{+-}1.1 for <10 years and 1.6{+-}0.9 for >10 years in the study group, while 0.1{+-}1.1 for <10 years and -0.2 {+-} 0.6 for >10 years in the control group, which also showed >statistically significant difference (<10 years p=0.04 and >10 years p<0.0001). These differences indicate that there was a delay in the maturation of bones by 1 year in the group <10

  11. Spondylectomy and lateral lumbar interbody fusion for thoracolumbar kyphosis in an adult with achondroplasia

    Science.gov (United States)

    Miyazaki, Masashi; Kanezaki, Shozo; Notani, Naoki; Ishihara, Toshinobu; Tsumura, Hiroshi

    2017-01-01

    Abstract Rationale: Fixed thoracolumbar kyphosis with spinal stenosis in adult patients with achondroplasia presents a challenging issue. We describe the first case in which spondylectomy and minimally invasive lateral access interbody arthrodesis were used for the treatment of fixed severe thoracolumbar kyphosis and lumbar spinal canal stenosis in an adult with achondroplasia. Patient concerns: A 61-year-old man with a history of achondroplastic dwarfism presented with low back pain and radiculopathy and neurogenic claudication. Diagnoses: Plain radiographs revealed a high-grade thoracolumbar kyphotic deformity with diffuse degenerative changes in the lumbar spine. The apex was located at L2, the local kyphotic angle from L1 to L3 was 105°, and the anterior area was fused from the L1 to L3 vertebrae. MRI revealed significant canal and lateral recess stenosis secondary to facet hypertrophy. Interventions: We planned a front-back correction of the anterior and posterior spinal elements. We first performed anterior release at the fused part from L1 to L3 and XLIF at L3/4 and L4/5. Next, the patient was placed in the prone position. Spondylectomy at the L2 vertebra and posterior fusion from T10 to L5 were performed. Postoperative radiographs revealed L1 to L3 kyphosis of 32°. Outcomes: No complications occurred during or after surgery. Postoperatively, the patient's low back pain and neurological claudication were resolved. No worsening of kyphosis was observed 24 months postoperatively. Lessons: Circumferential decompression of the spinal cord at the apical vertebral level and decompression of lumbar canal stenosis were necessary. Front-back correction of the anterior and posterior spinal elements via spondylectomy and lateral lumbar interbody fusion is a reasonable surgical option for thoracolumbar kyphosis and developmental canal stenosis in patients with achondroplasia. PMID:29245270

  12. MR imaging of the craniocervical junction, cranium, and brain in children with achondroplasia

    International Nuclear Information System (INIS)

    Kao, S.C.; Waziri, M.; Sato, Y.; Smith, W.L.; Yuh, W.T.C.; Franken, E.A. Jr.

    1988-01-01

    Ten children with achondroplasia underwent MR imaging of the craniocervical junction, cranium and brain. All patients had narrowing of the subarachnoid space at the level of foramen magnum with apparent upward displacement of the brain stem. Hydrocephalus was seen in five patients, bifrontal widening of subarachnoid space in four, skull asymmetry in two, and an empty sella in one. One patient showed abnormal signal in the central gray matter of the cervicomedullary region. MR is a noninvasive modality for the evaluation of cranial, cerebral, and cervicomedullary is achondroplastic children

  13. Emergency cesarean section in a patient with achondroplasia: A case report

    Directory of Open Access Journals (Sweden)

    M. Mokhtari

    2018-04-01

    Full Text Available Dwarfism occurs when a medical condition causes short stature due to slow growth. Achondroplasia is the commonest form of dwarfism. Some pregnancy problems like significant increase in cesarean section rate, respiratory distress towards the end of pregnancy, preterm labor and delivery and abortion are more prevalent in these patients. Management of pregnancy and delivery are challengeable for obstetricians and anesthesiologist and there are controversies. This case report discusses a 30-year-old achondroplastic primigravida Baluch woman at 37 weeks gestation. She weighed 44 kg and her height was 110 cm. The patient had an emergency cesarean section under general anesthesia.

  14. FGFR3 gene mutation plus GRB10 gene duplication in a patient with achondroplasia plus growth delay with prenatal onset.

    Science.gov (United States)

    Yuan, Haiming; Huang, Linhuan; Hu, Xizi; Li, Qian; Sun, Xiaofang; Xie, Yingjun; Kong, Shu; Wang, Xiaoman

    2016-07-02

    Achondroplasia is a well-defined and common bone dysplasia. Genotype- and phenotype-level correlations have been found between the clinical symptoms of achondroplasia and achondroplasia-specific FGFR3 mutations. A 2-year-old boy with clinical features consistent with achondroplasia and Silver-Russell syndrome-like symptoms was found to carry a mutation in the fibroblast growth factor receptor-3 (FGFR3) gene at c.1138G > A (p.Gly380Arg) and a de novo 574 kb duplication at chromosome 7p12.1 that involved the entire growth-factor receptor bound protein 10 (GRB10) gene. Using quantitative real-time PCR analysis, GRB10 was over-expressed, and, using enzyme-linked immunosorbent assays for IGF1 and IGF-binding protein-3 (IGFBP3), we found that IGF1 and IGFBP3 were low-expressed in this patient. We demonstrate that a combination of uncommon, rare and exceptional molecular defects related to the molecular bases of particular birth defects can be analyzed and diagnosed to potentially explain the observed variability in the combination of molecular defects.

  15. Chest wall deformity and respiratory distress in a 17-year-old patient with achondroplasia: CT and MRI evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Herman, T.E.; Siegel, M.J.; McAlister, W.H. (Washington Univ. School of Medicine, St. Louis, MO (United States). Mallinckrodt Inst. of Radiology)

    1992-06-01

    A marked thoracic deformity associated with intrathoracic tracheal narrowing was seen in a 17-year old with achondroplasia and dyspnea. The role of chest deformity and its evaluation by CT and MRI in achondroplastic patients with respiratory symptoms are considered. (orig.).

  16. Abnormal pelvic morphology and high cervical length are responsible for high-risk pregnancies in women displaying achondroplasia.

    Science.gov (United States)

    Vivanti, Alexandre J; Cordier, Anne-Gael; Baujat, Geneviève; Benachi, Alexandra

    2016-12-05

    Pregnancies of women displaying achondroplasia are at high risk of adverse events. Early sonographic assessment of affected women can indicate an unusually long cervical length. It is the consequence of pathological anatomy of the pelvis. Thus, there is a foreseeable dystocia owing to cephalopelvic disproportion. Furthermore, this situation could also complicate cervical ripening prior to fetal extraction.

  17. Magnetic resonance imaging study determining cord level and occupancy at thoracolumbar junction in achondroplasia - A prospective study

    Directory of Open Access Journals (Sweden)

    Hitesh N Modi

    2011-01-01

    Conclusion: Our results indicated high level of spinal cord in achondroplasia patients compared to nonachondroplasia individuals. High prevalence of neurological symptoms at TL level in such patients can be associated with high cord level and developing progressive kyphosis at TL level along with degenerative process.

  18. Achondroplasia with 47, XXY karyotype: a case report of the neonatal diagnosis of an extremely unusual association.

    Science.gov (United States)

    Ros-Pérez, Purificación; Regidor, Francisco J; Colino, Esmeralda; Martínez-Payo, Cristina; Barroso, Eva; Heath, Karen E

    2012-06-29

    The association of achondroplasia and Klinefelter syndrome is extremely rare. To date, five cases have been previously reported, all of them diagnosed beyond the postnatal period, and only one was molecularly characterized. We describe the first case of this unusual association diagnosed in the neonatal period, the clinical findings and the molecular studies undertaken. The boy was born at term with clinical and radiological features indicating the diagnosis of achondroplasia or hypochondroplasia combined with the prenatal karyotype of Klinefelter syndrome (47,XXY). Neonatal FGFR3 mutation screening showed that the newborn was heterozygous for the classic achondroplasia G340R mutation. Microsatellite marker analysis showed that the sex chromosome aneuploidy had arisen from a non-disjunction error in paternal meiosis I, with a recombination event in the pseudoautosomal region 1 (PAR1). Specific mutation analysis is appropriate to confirm the clinical diagnosis of achondroplasia for appropriate diagnosis, prognosis, and genetic counseling, especially when the karyotype does not explain the abnormal prenatal sonographic findings. In the present case, a recombination event was observed in the PAR1 region, although recombinational events in paternally derived Klinefelter syndrome cases are much rarer than expected.

  19. Achondroplasia in children: correlation of ventriculomegaly, size of foramen magnum and jugular foramina, and emissary vein enlargement.

    Science.gov (United States)

    Bosemani, Thangamadhan; Orman, Gunes; Hergan, Benedikt; Carson, Kathryn A; Huisman, Thierry A G M; Poretti, Andrea

    2015-01-01

    Achondroplasia is a skeletal dysplasia with diminished growth of the skull base secondary to defective enchondral bone formation. This leads to narrowing of the foramen magnum and jugular foramina, which further leads to ventricular dilatation and prominence of the emissary veins. The primary goal of our study was to determine a correlation between the degree of ventricular dilatation, jugular foramina and foramen magnum narrowing, as well as emissary vein enlargement. Conventional T2-weighted MR images were evaluated for surface area of the foramen magnum and jugular foramina, ventricular dilatation, and emissary veins enlargement in 16 achondroplasia patients and 16 age-matched controls. Ratios were calculated for the individual parameters using median values from age-matched control groups to avoid age as a confounder. Compared to age-matched controls, in children with achondroplasia, the surface area of the foramen magnum (median 0.50 cm(2), range 0.23-1.37 cm(2) vs. 3.14 cm(2), 1.83-6.68 cm(2), p achondroplasia, (1) the variation in ventricular dilatation may be related to an unquantifiable interdependent relationship of emissary vein enlargement, venous channel narrowing, and foramen magnum compression and (2) stable ventricular size facilitated by interdependent factors likely obviates the need for ventricular shunt placement.

  20. Achondroplasia with 47, xxy karyotype: a case report of the neonatal diagnosis of an extremely unusual association

    Directory of Open Access Journals (Sweden)

    Ros-Pérez Purificación

    2012-06-01

    Full Text Available Abstract Background The association of achondroplasia and Klinefelter syndrome is extremely rare. To date, five cases have been previously reported, all of them diagnosed beyond the postnatal period, and only one was molecularly characterized. We describe the first case of this unusual association diagnosed in the neonatal period, the clinical findings and the molecular studies undertaken. Case presentation The boy was born at term with clinical and radiological features indicating the diagnosis of achondroplasia or hypochondroplasia combined with the prenatal karyotype of Klinefelter syndrome (47,XXY. Neonatal FGFR3 mutation screening showed that the newborn was heterozygous for the classic achondroplasia G340R mutation. Microsatellite marker analysis showed that the sex chromosome aneuploidy had arisen from a non-disjunction error in paternal meiosis I, with a recombination event in the pseudoautosomal region 1 (PAR1. Conclusion Specific mutation analysis is appropriate to confirm the clinical diagnosis of achondroplasia for appropriate diagnosis, prognosis, and genetic counseling, especially when the karyotype does not explain the abnormal prenatal sonographic findings. In the present case, a recombination event was observed in the PAR1 region, although recombinational events in paternally derived Klinefelter syndrome cases are much rarer than expected.

  1. Chest wall deformity and respiratory distress in a 17-year-old patient with achondroplasia: CT and MRI evaluation

    International Nuclear Information System (INIS)

    Herman, T.E.; Siegel, M.J.; McAlister, W.H.

    1992-01-01

    A marked thoracic deformity associated with intrathoracic tracheal narrowing was seen in a 17-year old with achondroplasia and dyspnea. The role of chest deformity and its evaluation by CT and MRI in achondroplastic patients with respiratory symptoms are considered. (orig.)

  2. Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies

    Czech Academy of Sciences Publication Activity Database

    Kunová Bosáková, M.; Vařecha, M.; Hampl, Marek; Duran, I.; Nita, A.; Buchtová, Marcela; Dosedělová, Hana; Machat, R.; Xie, Y.; Ni, Z.; Martin, J. H.; Chen, L.; Jansen, G.; Krakow, D.; Krejčí, P.

    2018-01-01

    Roč. 27, č. 6 (2018), s. 1093-1105 ISSN 0964-6906 R&D Projects: GA MŠk EF15_003/0000460 Institutional support: RVO:67985904 Keywords : achondroplasia * thanatophoric dysplasia Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Developmental biology Impact factor: 5.340, year: 2016

  3. Reverse shoulder arthroplasty in young patient with achondroplasia - Ten year follow up: Case report.

    Science.gov (United States)

    van den Broek, M; Verborgt, O; Declercq, G

    2017-11-01

    Skeletal dysplasia in achondroplasia can affect all body joints - including the glenohumeral joint - and is prone to develop to degenerative osteoarthritis (OA). This may cause pain and mobility problems at young age. Surgical treatment is challenging due to the dysplastic anatomy of the shoulder joint - with a dysplastic deformed short humerus, a small, hypoplastic medialized glenoid and lateralized acromion - and the long life expectancy of these patients. The indications for reverse shoulder arthroplasty (RSA) evolved during years with rotator cuff tears and rotator cuff arthropathy in combination with or without glenohumeral OA as the main indicator, with good short to mid-term results. Long term results of RSA are rarely found in literature, especially in young patients. The use of a RSA in glenohumeral OA with an intact rotator cuff has rarely been reported. In this case report we present the ten-year clinical and radiographic results of a RSA for the treatment of degenerative OA with glenohumeral dysplasia in a young patient with achondroplasia. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect

    Science.gov (United States)

    Tiemann-Boege, Irene; Navidi, William; Grewal, Raji; Cohn, Dan; Eskenazi, Brenda; Wyrobek, Andrew J.; Arnheim, Norman

    2002-01-01

    The lifelong spermatogonial stem cell divisions unique to male germ cell production are thought to contribute to a higher mutation frequency in males. The fact that certain de novo human genetic conditions (e.g., achondroplasia) increase in incidence with the age of the father is consistent with this idea. Although it is assumed that the paternal age effect is the result of an increasing frequency of mutant sperm as a man grows older, no direct molecular measurement of the germ-line mutation frequency has been made to confirm this hypothesis. Using sperm DNA from donors of different ages, we determined the frequency of the nucleotide substitution in the fibroblast growth factor receptor 3 (FGFR3) gene that causes achondroplasia. Surprisingly, the magnitude of the increase in mutation frequency with age appears insufficient to explain why older fathers have a greater chance of having a child with this condition. A number of alternatives may explain this discrepancy, including selection for sperm that carry the mutation or an age-dependent increase in premutagenic lesions that remain unrepaired in sperm and are inefficiently detected by the PCR assay. PMID:12397172

  5. Achondroplasia among ancient populations of mesoamerica and South America: Iconographic and Archaeological Evidence.

    Science.gov (United States)

    Isaza, Carolina; Pachajoa, Harry

    2012-01-01

    Introduction: Achondroplasia is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and mid-face hypoplasia, genu varum, and trident hand. Although the etiology of this disease was reported in 1994, evidence of this disease in ancient populations has been found in populations of ancient Egypt (2500 BC) and it has been documented in ancient American populations. Objective: To analyze the presence of individuals with achondroplasia in the Mayan state society of Mexico and Guatemala, during the Classical (100- 950 AC ) and Post-Classical (950 - 1519 AC ) periods; likewise, in the hierarchical-chieftain society of Tumaco-la Tolita (300 BC - 600 AC ) from the Colombia-Ecuador Pacific coast, and the Moche state society (100 - 600 AC ) from the northern coast of Peru. Methods: Iconographic and clinical-morphological studies of some of the most important artistic representations of individuals of short stature in these three cultures. Conclusion: We present the hypothesis that the individuals with short stature were somehow associated with the political and religious power elite. PMID:24893194

  6. Osteological evidence of short-limbed dwarfism in a nineteenth century Dutch family: Achondroplasia or hypochondroplasia.

    Science.gov (United States)

    Waters-Rist, Andrea L; Hoogland, Menno L P

    2013-12-01

    An opportunity to explore osteological features of a form of disproportionate dwarfism is presented by a recent archaeological discovery. Excavation of a predominately nineteenth century Dutch cemetery from the rural, agricultural village of Middenbeemster revealed an older adult female with skeletal changes consistent with achondroplasia. The most marked features are a rhizomelic pattern of shortened and thickened upper and lower limbs, frontal bossing and a moderately depressed nasal bridge, small lumbar neural canals with short pedicles, bowing of the femora and tibiae, and short stature (130.0±5cm). However, some common features of achondroplasia like cranial base reduction and shortened fingers and toes are absent. The alternative diagnosis of a more mild form of short-limbed dwarfism, hypochondroplasia, is explored and aided by archival identification of the individual and her offspring. Five offspring, including three perinates, a 10-year-old daughter, and a 21-year-old son, are analysed for evidence of an inherited skeletal dysplasia. The unique addition of family history to the paleopathological diagnostic process supports a differential outcome of hypochondroplasia. This combination of osteological and archival data creates a unique opportunity to track the inheritance and manifestation of a rare disease in a past population. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. NMR images of non-communicating hydrocephalus associated with Dandy-Walker variant and achondroplasia

    International Nuclear Information System (INIS)

    Sato, Masaharu; Kuroda, Ryotaro; Watanabe, Masaru; Nakatani, Jiro; Ioku, Masahiko; Irisawa, Minoru; Hamada, Tatsumi; Ishida, Osamu

    1988-01-01

    Two cases of non-communicating hydrocephalus caused by a relatively rare etiology were reported. They were both diagnosed by means of nuclear magnetic resonance (NMR). The first patient, a 4-month-old boy, had Dandy-Walker variant, showing hypoplasia of the corpus callosum and the inferior vermis, and a large cyst behind the vermis, communicating with the subarachnoid space, as well as hydrocephalus; the fourth ventricle was partially reserved. The second patient, also a 4-month-old boy, had achondroplasia, resulting in a narrow foramen magnum; the disturbance of the outflow of the cerebro-spinal fluid around the cisterna magna was thought to be the cause of hydrocephalus in his case. The validity of NMR was demonstrated in the diagnoses of these conditions, for a high resolution was needed in examining the complicated structure of the posterior fossa. (author)

  8. NMR images of non-communicating hydrocephalus associated with Dandy-Walker variant and achondroplasia

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Masaharu; Kuroda, Ryotaro; Watanabe, Masaru; Nakatani, Jiro; Ioku, Masahiko; Irisawa, Minoru; Hamada, Tatsumi; Ishida, Osamu

    1988-06-01

    Two cases of non-communicating hydrocephalus caused by a relatively rare etiology were reported. They were both diagnosed by means of nuclear magnetic resonance (NMR). The first patient, a 4-month-old boy, had Dandy-Walker variant, showing hypoplasia of the corpus callosum and the inferior vermis, and a large cyst behind the vermis, communicating with the subarachnoid space, as well as hydrocephalus; the fourth ventricle was partially reserved. The second patient, also a 4-month-old boy, had achondroplasia, resulting in a narrow foramen magnum; the disturbance of the outflow of the cerebro-spinal fluid around the cisterna magna was thought to be the cause of hydrocephalus in his case. The validity of NMR was demonstrated in the diagnoses of these conditions, for a high resolution was needed in examining the complicated structure of the posterior fossa.

  9. Favorable Growth Hormone Treatment Response in a Young Boy with Achondroplasia.

    Science.gov (United States)

    Krstevska-Konstantinova, Marina; Stamatova, Ana; Gucev, Zoran

    2016-04-01

    Achondroplasia is a skeletal dysplasia, the most common cause of rhizomelic dwarfism. This is a ten year old boy who was first diagnosed prenatally. He had a mutation c1138G>A in the gene FGFR3 in a heterozygotic constellation. His IGF1 and IGFBP3 levels were normal. Two stimulation tests for growth hormone were performed with values within the reference range. His psychomotor development was adequate for his age except for speech difficulty. He started with recombinant hGH (r-hGH) at the age of 3.4 years in a dose of 0.06 mg/kg. His mean Height SDS (HtSDS) was -2.2. The growth increased to 10 cm/year in the first year of therapy (HtSDS -1.1). It decreased during the second year to 4 cm (HtSDS -1.7) and again increased during the third year to 8 cm/year (HtSDS-1.3). In the next years the growth was constant (6.5, 2.3, 3.5 cm / year). He is still growing in the 3(rd) percentile of the growth curve (HtSDS - 1.2) under GH treatment. The body disproportion remained the same. The growth response on GH treatment was satisfactory in the first 4 years of treatment, and the boy still continued to grow. The young age at the start of treatment was also of importance. Our other patients with achondroplasia who started treatment older had a poor response to growth hormone.

  10. [Achondroplasia: a pilot study on the psychosocial and medical features of a sample in Puerto Rico].

    Science.gov (United States)

    Rodriguez-Gomez, José; Aldarondo, Ariadna; Vidot, Frances; Quiñones, Ana; Rivera, Maily; Cintrón, Eledy; Gonzilez, Natalie; Trujillo, Rodolfo F; Lopez-Cordova, Nanet M; Colón, Natalia

    2015-01-01

    This study explores the psychological wellbeing of twenty-two (n = 22) adults with achondroplasia. The sample was composed of seven (n = 7) males and fifteen (n = 15) females between the ages of 21 and 75 (mean age = 39.6). Each individual completed four self-administered questionnaires: the Beck Depression Inventory (BDI-l), the Beck Anxiety Inventory (BAI), the Beck Hopelessness Scale (BHS), and Derogatis Symptom Check-list-90-Revisited (SCL-90-R). They also filled out a socio-demographic questionnaire. We found that 31.8% of the sample reported at least one comorbid condition such as, hypertension, diabetes, rheumatoid arthritis, asthma, scoliosis, thyroid problems, neuropathy, psoriasis, gastritis and/or sleep apnea; 32% reported mild to severe depressive symp- toms; 55% reported mild to severe symptoms associated to anxiety and 18% reported mild to severe symptoms associated with hopelessness; 22.7% reported mild to severe symptoms in at least one of the sub-scales in Derogatis Symptom Checklist-90-Revisited (SCL-90-R) particularly the obsessive-compulsive, paranoid and depressive subscales. Chi Square correlations (X2) were made to observe if there was interdependence between the socio-demographic variables and the administered tests. In general, no significant correlations were found between BDI-Il, BAI, BHS, SCL-90-R and civil status, gender, income and age. However, a significant correlation was found between age and the somatization sub-scale of the SCL-90-R (rs = 0.510, p achondroplasia. The development of preventive and cultural sensitive interventions is suggested in order to protect and treat individuals with the condition.

  11. Surgical decompression of thoracic spinal stenosis in achondroplasia: indication and outcome.

    Science.gov (United States)

    Vleggeert-Lankamp, Carmen; Peul, Wilco

    2012-08-01

    The achondroplastic spinal canal is narrow due to short pedicles and a small interpedicular distance. Compression of neural structures passing through this canal is therefore regularly encountered but rarely described. Symptomatology, radiological evaluation, and treatment of 20 patients with achondroplasia who underwent decompression of the thoracic spinal cord are described and outcome is correlated with the size of the spinal canal and the thoracolumbar kyphotic angle. Scores from the modified Japanese Orthopaedic Association scale, Nurick scale, European Myelopathy scale, Cooper myelopathy scale for lower extremities, and Odom criteria before and after surgery were compared. Magnetic resonance imaging was evaluated to determine the size of the spinal canal, spinal cord compression, and presence of myelomalacia. The thoracolumbar kyphotic angle was measured using fluoroscopy. Patient symptomatology included deterioration of walking pattern, pain, cramps, spasms, and incontinence. Magnetic resonance images of all patients demonstrated spinal cord compression due to degenerative changes. Surgery resulted in a slight improvement on all the ranking scales. Surgery at the wrong level occurred in 15% of cases, but no serious complications occurred. The mean thoracolumbar kyphotic angle was 20°, and no correlation was established between this angle and outcome after surgery. No postoperative increase in this angle was reported. There was also no correlation between size of the spinal canal and outcome. Decompressive surgery of the thoracic spinal cord in patients with achondroplasia can be performed safely if anatomical details are taken into consideration. Spondylodesis did not appear essential. Special attention should be given to the method of surgery, identification of the level of interest, and follow-up of the thoracolumbar kyphotic angle.

  12. Bilateral humeral lengthening in achondroplasia with unilateral external fixators: is it safe and does it improve daily life?

    Science.gov (United States)

    Balci, H I; Kocaoglu, M; Sen, C; Eralp, L; Batibay, S G; Bilsel, K

    2015-11-01

    A retrospective study was performed in 18 patients with achondroplasia, who underwent bilateral humeral lengthening between 2001 and 2013, using monorail external fixators. The mean age was ten years (six to 15) and the mean follow-up was 40 months (12 to 104). The mean disabilities of the arm, shoulder and hand (DASH) score fell from 32.3 (20 to 40) pre-operatively to 9.4 (6 to 14) post-operatively (p = 0.037). A mean lengthening of 60% (40% to 95%) was required to reach the goal of independent perineal hygiene. One patient developed early consolidation, and fractures occurred in the regenerate bone of four humeri in three patients. There were three transient radial nerve palsies. Humeral lengthening increases the independence of people with achondroplasia and is not just a cosmetic procedure. ©2015 The British Editorial Society of Bone & Joint Surgery.

  13. Two-staged Bilateral, Femoral Alignment Osteotomy with Concomitant Total Knee Arthroplasty in an Achondroplasia Patient - A Case Report

    Science.gov (United States)

    Walter, Sebastian G; Schwering, Tobias; Preiss, Stefan

    2017-01-01

    Introduction: Achondroplasia is the most common form of dwarfism in humans and is orthopedically characterized by shortened extremities and an exaggerated lumbar lordosis. The surgical challenges are maintenance of axial alignment during limb lengthening as well as joint preservation and alignment restoration. Case Report: We present a 46-year-old female suffering from achondroplasia with severe pain in both knees. Severe varus deformities of both femurs and degeneration of both knee joints became apparent on clinical and radiological examination. On each femur, we performed one-staged, lateral closed-wedge osteotomy, and total knee arthroplasty (TKA). Subsequently, the patient was relieved of knee joint pain and gained a greater range of motion. Conclusion: One-staged valgization osteotomy and concomitant TKA represents a challenging, yet reasonable, surgical solution in axially severe malaligned and joint degenerated patients. PMID:28819598

  14. Is bilateral lower limb lengthening appropriate for achondroplasia?: midterm analysis of the complications and quality of life.

    Science.gov (United States)

    Kim, Seung-Ju; Balce, Gracia Cielo; Agashe, Mandar Vikas; Song, Sang-Heon; Song, Hae-Ryong

    2012-02-01

    Use of the Ilizarov technique for limb lengthening in patients with achondroplasia is controversial, with a high risk of complications balancing cosmetic gains. Although several articles have described the complications of this procedure and satisfaction of patients after surgery, it remains unclear whether lengthening improves the quality of life (QOL) of these patients. We asked whether bilateral lower limb lengthenings with deformity correction in patients with achondroplasia would improve QOL and investigated the correlation between complication rate and QOL. We retrospectively reviewed 22 patients (average age, 12.7 years) diagnosed with achondroplasia who underwent bilateral lower limb lengthenings between 2002 and 2005. These patients were compared with 22 patients with achondroplasia for whom limb lengthening was not performed. The two groups were assessed using the American Academy of Orthopaedic Surgeons (AAOS) lower limb, SF-36, and Rosenberg self-esteem scores. Minimum followup was 4.5 years (range, 4.5-6.9 years). Among the lengthening group, the average gain in length was 10.21 ± 2.39 cm for the femur and 9.13 ± 2.12 cm for the tibia. A total of 123 complications occurred in these 88 segments. The surgical group had higher Rosenberg self-esteem scores than the nonsurgical group although there were no differences in the AAOS and the SF-36 scores. The self-esteem scores decreased with the increase in the number of complications. Our data suggest that despite frequent complications, bilateral lower limb lengthening increases patients' QOL. We believe lengthening is a reasonable option in selected patients. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

  15. C-type natriuretic peptide plasma levels are elevated in subjects with achondroplasia, hypochondroplasia, and thanatophoric dysplasia.

    Science.gov (United States)

    Olney, Robert C; Prickett, Timothy C R; Espiner, Eric A; Mackenzie, William G; Duker, Angela L; Ditro, Colleen; Zabel, Bernhard; Hasegawa, Tomonobu; Kitoh, Hiroshi; Aylsworth, Arthur S; Bober, Michael B

    2015-02-01

    C-type natriuretic peptide (CNP) is a crucial regulator of endochondral bone growth. In a previous report of a child with acromesomelic dysplasia, Maroteaux type (AMDM), caused by loss-of-function of the CNP receptor (natriuretic peptide receptor-B [NPR-B]), plasma levels of CNP were elevated. In vitro studies have shown that activation of the MAPK kinase (MEK)/ERK MAPK pathway causes functional inhibition of NPR-B. Achondroplasia, hypochondroplasia, and thanatophoric dysplasia are syndromes of short-limbed dwarfism caused by activating mutations of fibroblast growth factor receptor-3, which result in overactivation of the MEK/ERK MAPK pathway. The purpose of this study was to determine whether these syndromes exhibit evidence of CNP resistance as reflected by increases in plasma CNP and its amino-terminal propeptide (NTproCNP). This was a prospective, observational study. Participants were 63 children and 20 adults with achondroplasia, 6 children with hypochondroplasia, 2 children with thanatophoric dysplasia, and 4 children and 1 adult with AMDM. Plasma levels of CNP and NTproCNP were higher in children with achondroplasia with CNP SD scores (SDSs) of 1.0 (0.3-1.4) (median [interquartile range]) and NTproCNP SDSs of 1.4 (0.4-1.8; P achondroplasia (CNP SDSs of 1.5 [0.7-2.1] and NTproCNP SDSs of 0.5 [0.1-1.0], P < .005). In children with hypochondroplasia, CNP SDSs were 1.3 (0.7-1.5) (P = .08) and NTproCNP SDSs were 1.9 (1.8-2.3) (P < .05). In children with AMDM, CNP SDSs were 1.6 (1.4-3.3) and NTproCNP SDSs were 4.2 (2.7-6.2) (P < .01). In these skeletal dysplasias, elevated plasma levels of proCNP products suggest the presence of tissue resistance to CNP.

  16. Common mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene account for achondroplasia, hypochondroplasia, and thanatophoric dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Bonaventure, J.; Rousseau, F.; Legeai-Mallet, L.; LeMerrer, M.; Munnich, A.; Maroteaux, P. [INSERM, Paris (France)

    1996-05-03

    The mapping of the achondroplasia locus to the short arm of chromosome 4 and the subsequent identification of a recurrent missense mutation (G380R) in the fibroblast growth factor receptor 3 (FGFR-3) gene has been followed by the detection of common FGFR-3 mutations in two clinically related disorders: thanatophoric dwarfism (types I and II) and hypochondroplasia. The relative clinical homogeneity of achondroplasia was substantiated by demonstration of its genetic homogeneity as more than 98% of all patients hitherto reported exhibit mutations in the transmembrane receptor domain. Although most hypochondroplasia cases were accounted for by a recurrent missense substitution (N540K) in the first tyrosine kinase (TK 1) domain of the receptor, a significant proportion (40%) of our patients did not harbor the N540K mutation and three hypochondroplasia families were not linked to the FGFR-3 locus, thus supporting clinical heterogeneity of this condition. In thanatophoric dwarfism (TD), a recurrent FGFR-3 mutation located in the second tyrosine kinase (TK 2) domain of the receptor was originally detected in 100% of TD II cases; in our series, seven distinct mutations in three different protein domains were identified in 25 of 26 TD I patients, suggesting that TD, like achondroplasia, is a genetically homogenous skeletal disorder. 31 refs., 4 figs., 2 tabs.

  17. Droplet digital PCR combined with minisequencing, a new approach to analyze fetal DNA from maternal blood: application to the non-invasive prenatal diagnosis of achondroplasia.

    Science.gov (United States)

    Orhant, Lucie; Anselem, Olivia; Fradin, Mélanie; Becker, Pierre Hadrien; Beugnet, Caroline; Deburgrave, Nathalie; Tafuri, Gilles; Letourneur, Franck; Goffinet, François; Allach El Khattabi, Laïla; Leturcq, France; Bienvenu, Thierry; Tsatsaris, Vassilis; Nectoux, Juliette

    2016-05-01

    Achondroplasia is generally detected by abnormal prenatal ultrasound findings in the third trimester of pregnancy and then confirmed by molecular genetic testing of fetal genomic DNA obtained by aspiration of amniotic fluid. This invasive procedure presents a small but significant risk for both the fetus and mother. Therefore, non-invasive procedures using cell-free fetal DNA in maternal plasma have been developed for the detection of the fetal achondroplasia mutations. To determine whether the fetus carries the de novo mis-sense genetic mutation at nucleotide 1138 in FGFR3 gene involved in >99% of achondroplasia cases, we developed two independent methods: digital-droplet PCR combined with minisequencing, which are very sensitive methods allowing detection of rare alleles. We collected 26 plasmatic samples from women carrying fetus at risk of achondroplasia and diagnosed to date a total of five affected fetuses in maternal blood. The sensitivity and specificity of our test are respectively 100% [95% confidence interval, 56.6-100%] and 100% [95% confidence interval, 84.5-100%]. This novel, original strategy for non-invasive prenatal diagnosis of achondroplasia is suitable for implementation in routine clinical testing and allows considering extending the applications of these technologies in non-invasive prenatal diagnosis of many other monogenic diseases. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  18. Height Outcome of Recombinant Human Growth Hormone Treatment in Achondroplasia Children: A Meta-Analysis.

    Science.gov (United States)

    Miccoli, Mario; Bertelloni, Silvano; Massart, Francesco

    2016-01-01

    Although recombinant human growth hormone (rhGH) is not approved to treat short stature of achondroplasia (ACH), some studies suggested growth improvement during short-term rhGH treatment. A meta-analysis of rhGH therapy efficacy in ACH children was performed. From 12 English-language studies, 558 (54.0% males) rhGH-treated ACH children were enrolled. Administration of rhGH (median dosage 0.21 mg/kg/ week; range 0.16-0.42 mg/kg/week) improved height (Ht) from baseline [-5.069 standard deviation score (SDS; 95% CI -5.109 to -5.029); p < 0.0001] to 12 [-4.325 SDS (95% CI -4.363 to -4.287); p < 0.0001] and 24 months [-4.073 SDS (95% CI -4.128 to -4.019); p < 0.0001]. Then, Ht remained approximately constant up to 5 years [-3.941 SDS (95% CI -4.671 to -3.212); p < 0.0001]. In ACH children, rhGH treatment increased Ht from -5.0 to -4.0 SDS during 5 years, but insufficient data are available on both the adult Ht and the changes of body proportions. © 2016 S. Karger AG, Basel.

  19. Meckel's and condylar cartilages anomalies in achondroplasia result in defective development and growth of the mandible.

    Science.gov (United States)

    Biosse Duplan, Martin; Komla-Ebri, Davide; Heuzé, Yann; Estibals, Valentin; Gaudas, Emilie; Kaci, Nabil; Benoist-Lasselin, Catherine; Zerah, Michel; Kramer, Ina; Kneissel, Michaela; Porta, Diana Grauss; Di Rocco, Federico; Legeai-Mallet, Laurence

    2016-07-15

    Activating FGFR3 mutations in human result in achondroplasia (ACH), the most frequent form of dwarfism, where cartilages are severely disturbed causing long bones, cranial base and vertebrae defects. Because mandibular development and growth rely on cartilages that guide or directly participate to the ossification process, we investigated the impact of FGFR3 mutations on mandibular shape, size and position. By using CT scan imaging of ACH children and by analyzing Fgfr3 Y367C/+ mice, a model of ACH, we show that FGFR3 gain-of-function mutations lead to structural anomalies of primary (Meckel's) and secondary (condylar) cartilages of the mandible, resulting in mandibular hypoplasia and dysmorphogenesis. These defects are likely related to a defective chondrocyte proliferation and differentiation and pan-FGFR tyrosine kinase inhibitor NVP-BGJ398 corrects Meckel's and condylar cartilages defects ex vivo. Moreover, we show that low dose of NVP-BGJ398 improves in vivo condyle growth and corrects dysmorphologies in Fgfr3 Y367C/+ mice, suggesting that postnatal treatment with NVP-BGJ398 mice might offer a new therapeutic strategy to improve mandible anomalies in ACH and others FGFR3-related disorders. © The Author 2016. Published by Oxford University Press.

  20. Spondylectomy and lateral lumbar interbody fusion for thoracolumbar kyphosis in an adult with achondroplasia: A case report.

    Science.gov (United States)

    Miyazaki, Masashi; Kanezaki, Shozo; Notani, Naoki; Ishihara, Toshinobu; Tsumura, Hiroshi

    2017-12-01

    Fixed thoracolumbar kyphosis with spinal stenosis in adult patients with achondroplasia presents a challenging issue. We describe the first case in which spondylectomy and minimally invasive lateral access interbody arthrodesis were used for the treatment of fixed severe thoracolumbar kyphosis and lumbar spinal canal stenosis in an adult with achondroplasia. A 61-year-old man with a history of achondroplastic dwarfism presented with low back pain and radiculopathy and neurogenic claudication. Plain radiographs revealed a high-grade thoracolumbar kyphotic deformity with diffuse degenerative changes in the lumbar spine. The apex was located at L2, the local kyphotic angle from L1 to L3 was 105°, and the anterior area was fused from the L1 to L3 vertebrae. MRI revealed significant canal and lateral recess stenosis secondary to facet hypertrophy. We planned a front-back correction of the anterior and posterior spinal elements. We first performed anterior release at the fused part from L1 to L3 and XLIF at L3/4 and L4/5. Next, the patient was placed in the prone position. Spondylectomy at the L2 vertebra and posterior fusion from T10 to L5 were performed. Postoperative radiographs revealed L1 to L3 kyphosis of 32°. No complications occurred during or after surgery. Postoperatively, the patient's low back pain and neurological claudication were resolved. No worsening of kyphosis was observed 24 months postoperatively. Circumferential decompression of the spinal cord at the apical vertebral level and decompression of lumbar canal stenosis were necessary. Front-back correction of the anterior and posterior spinal elements via spondylectomy and lateral lumbar interbody fusion is a reasonable surgical option for thoracolumbar kyphosis and developmental canal stenosis in patients with achondroplasia.

  1. Growth disturbance after lengthening of the lower limb and quantitative assessment of physeal closure in skeletally immature patients with achondroplasia.

    Science.gov (United States)

    Song, S H; Kim, S E; Agashe, M V; Lee, H; Refai, M A; Park, Y E; Choi, H J; Park, J H; Song, H R

    2012-04-01

    This study evaluated the effect of limb lengthening on longitudinal growth in patients with achondroplasia. Growth of the lower extremity was assessed retrospectively by serial radiographs in 35 skeletally immature patients with achondroplasia who underwent bilateral limb lengthening (Group 1), and in 12 skeletally immature patients with achondroplasia who did not (Group 2). In Group 1, 23 patients underwent only tibial lengthening (Group 1a) and 12 patients underwent tibial and femoral lengthening sequentially (Group 1b). The mean lengthening in the tibia was 9.2 cm (59.5%) in Group 1a, and 9.0 cm (58.2%) in the tibia and 10.2 cm (54.3%) in the femur in Group 1b. The mean follow-up was 9.3 years (8.6 to 10.3). The final mean total length of lower extremity in Group 1a was 526.6 mm (501.3 to 552.9) at the time of skeletal maturity and 610.1 mm (577.6 to 638.6) in Group 1b, compared with 457.0 mm (411.7 to 502.3) in Group 2. However, the mean actual length, representing the length solely grown from the physis without the length of distraction, showed that there was a significant disturbance of growth after limb lengthening. In Group 1a, a mean decrease of 22.4 mm (21.3 to 23.1) (4.9%) was observed in the actual limb length when compared with Group 2, and a greater mean decrease of 38.9 mm (37.2 to 40.8) (8.5%) was observed in Group 1b when compared with Group 2 at skeletal maturity. In Group 1, the mean actual limb length was 16.5 mm (15.8 to 17.2) (3.6%) shorter in Group 1b when compared with Group 1a at the time of skeletal maturity. Premature physeal closure was seen mostly in the proximal tibia and the distal femur with relative preservation of proximal femur and distal tibia. We suggest that significant disturbance of growth can occur after extensive limb lengthening in patients with achondroplasia, and therefore, this should be included in pre-operative counselling of these patients and their parents.

  2. Psychosocial Adjustment of Children with Short Stature (Achondroplasia): Social Competence, Behavior Problems, Self-Esteem, Family Functioning, Body Image, and Reaction to Frustrations.

    Science.gov (United States)

    Csapo, Marg

    1991-01-01

    This evaluation of 16 children (ages 7-12) with achondroplasia from Transkei, Hungary, and Nigeria found that, compared to controls, subjects had more behavior problems and less self-esteem. Subjects were socially withdrawn, internalized emotional problems, had lower academic performance, found less adaptive solutions to frustration, and faced…

  3. Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 Lys650Met mutation.

    NARCIS (Netherlands)

    Zankl, A.; Elakis, G.; Susman, R.D.; Inglis, G.; Gardener, G.; Buckley, M.F.; Roscioli, T.

    2008-01-01

    We present prenatal and postnatal features of a patient with severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN). Mutation analysis confirmed the clinical diagnosis by detecting the FGFR3 Lys650Met mutation. This case, one of only six with molecular analysis reported in

  4. Suppression of severe achondroplasia with developmental delay and acanthosis nigricans by the p.Thr651Pro mutation.

    Science.gov (United States)

    Manickam, Kandamurugu; Donoghue, Daniel J; Meyer, April N; Snyder, Pamela J; Prior, Thomas W

    2014-01-01

    Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) is an extremely rare severe skeletal dysplasia characterized by significant developmental delay, brain structural abnormalities, hearing loss, and acanthosis nigricans. The disorder is the result of a single missense mutation at codon 650 (p.Lys650Met) in the fibroblast growth factor receptor 3 gene (FGFR3). We describe a child who initially presented with a mild achondroplasia or hypochondroplasia like phenotype. Molecular analysis of the FGFR3 gene showed the common SADDAN mutation and a second novel mutation at codon 651 (p.Thr651Pro). Both mutations were shown to occur on the same allele (cis) and de novo. Transient transfection studies with FGFR3 double mutant constructs show that the p.Thr651Pro mutation causes a dramatic decrease in constitutive receptor kinase activity than that observed by the p.Lys650Met mutation. Our data suggest that the molecular effect by the p.Thr651Pro is to elicit a conformational change that decreases the FGFR3 tyrosine kinase activity, which is constitutively activated by the SADDAN mutation. Due to the inheritance of both a gain-of-function and a loss-of-function mutation, we conclude that a reduction of constitutive activation caused the milder skeletal phenotype. Although the occurrence of double mutations are expected to be rare, the presence of other FGFR3 modifiers may be responsible for some of the clinically discrepant skeletal dysplasia cases. © 2013 Wiley Periodicals, Inc.

  5. 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.

  6. New evidence for positive selection helps explain the paternal age effect observed in achondroplasia

    Science.gov (United States)

    Shinde, Deepali N.; Elmer, Dominik P.; Calabrese, Peter; Boulanger, Jérôme; Arnheim, Norman; Tiemann-Boege, Irene

    2013-01-01

    There are certain de novo germline mutations associated with genetic disorders whose mutation rates per generation are orders of magnitude higher than the genome average. Moreover, these mutations occur exclusively in the male germ line and older men have a higher probability of having an affected child than younger ones, known as the paternal age effect (PAE). The classic example of a genetic disorder exhibiting a PAE is achondroplasia, caused predominantly by a single-nucleotide substitution (c.1138G>A) in FGFR3. To elucidate what mechanisms might be driving the high frequency of this mutation in the male germline, we examined the spatial distribution of the c.1138G>A substitution in a testis from an 80-year-old unaffected man. Using a technology based on bead-emulsion amplification, we were able to measure mutation frequencies in 192 individual pieces of the dissected testis with a false-positive rate lower than 2.7 × 10−6. We observed that most mutations are clustered in a few pieces with 95% of all mutations occurring in 27% of the total testis. Using computational simulations, we rejected the model proposing an elevated mutation rate per cell division at this nucleotide site. Instead, we determined that the observed mutation distribution fits a germline selection model, where mutant spermatogonial stem cells have a proliferative advantage over unmutated cells. Combined with data on several other PAE mutations, our results support the idea that the PAE, associated with a number of Mendelian disorders, may be explained primarily by a selective mechanism. PMID:23740942

  7. Functional characteristics of mesenchymal stem cells derived from the adipose tissue of a patient with achondroplasia.

    Science.gov (United States)

    Park, Jeong-Ran; Lee, Hanbyeol; Kim, Chung-Hyo; Hong, Seok-Ho; Ha, Kwon-Soo; Yang, Se-Ran

    2016-05-01

    Mesenchymal stem cells (MSCs) can be isolated from various tissues including bone marrow, adipose tissue, skin dermis, and umbilical Wharton's jelly as well as injured tissues. MSCs possess the capacity for self-renewal and the potential for differentiation into adipogenic, osteogenic, and chondrogenic lineages. However, the characteristics of MSCs in injured tissues, such as achondroplasia (ACH), are not well known. In this study, we isolated MSCs from human subcutaneous adipose (ACH-SAMSCs) tissue and circumjacent human adipose tissue of the cartilage (ACH-CAMSCs) from a patient with ACH. We then analyzed the characterization of ACH-SAMSCs and ACH-CAMSCs, compared with normal human dermis-derived MSCs (hDMSCs). In flow cytometry analysis, the isolated ACH-MSCs expressed low levels of CD73, CD90, and CD105, compared with hDMSCs. Moreover, both ACH- SAMSCs and ACH-CAMSCs had constitutionally overactive fibroblast growth factor receptor 3 (FGFR3) and exhibited significantly reduced osteogenic differentiation, compared to enhanced adipogenic differentiation. The activity of extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK) was increased in ACH-MSCs. In addition, the efficacy of osteogenic differentiation was slightly restored in osteogenic differentiation medium with MAPKs inhibitors. These results suggest that they play essential roles in MSC differentiation toward adipogenesis in ACH pathology. In conclusion, the identification of the characteristics of ACH-MSCs and the favoring of adipogenic differentiation via the FGFR3/MAPK axis might help to elucidate the pathogenic mechanisms relevant to other skeletal diseases and could provide targets for therapeutic interventions.

  8. Callus features of regenerate fracture cases in femoral lengthening in achondroplasia

    International Nuclear Information System (INIS)

    Devmurari, Kamlesh N.; Song, Hae Ryong; Modi, Hitesh N.; Venkatesh, K.P.; Ju, Kim Seung; Song, Sang Heon

    2010-01-01

    We studied the callus features seen in cases of regenerate fracture in femoral lengthening using a monolateral fixator in achondroplasia to determine whether callus types and shapes can predict the probability of callus fracture. The radiographs of 28 cases of femoral lengthening in 14 patients, 14 cases of callus fracture, and 14 cases without callus fracture were retrospectively analyzed by four observers and classified into different shapes and types in concordance with the Ru Li classification. The average lengthening of 9.4 cm (range 7.5-11.8 cm) was achieved, which was 41% (range 30-55%) of the original length and the average timing of callus fracture was 470 days (range 440-545 days) after surgery in the callus fracture group. While the average lengthening of 9.1 cm (range 8-9.7 cm) was achieved, this was 30% (range 28-32%) of the original length in the group of patients without callus fracture. The callus was atypically shaped, there was a 48% average (range 30-72%) reduction of the callus width compared with the natural width of the femur, and a lucent pathway was present in all cases of regenerate fracture. A lucent pathway was seen in all fracture cases with concave, lateral, and atypical shapes, and there was more than 30% lengthening and 30% reduction of the callus width compared with the natural width of the femur, which are the warning signs for regenerate fractures. These signs help the surgeon to predict the outcome and guide him in planning for any additional interventions. The Ru Li classification is an effective method for the evaluation of the chance of callus fracture. (orig.)

  9. Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia.

    Directory of Open Access Journals (Sweden)

    Masaki Matsushita

    Full Text Available Achondroplasia (ACH is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8 cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias.

  10. Final adult height in long-term growth hormone-treated achondroplasia patients.

    Science.gov (United States)

    Harada, Daisuke; Namba, Noriyuki; Hanioka, Yuki; Ueyama, Kaoru; Sakamoto, Natsuko; Nakano, Yukako; Izui, Masafumi; Nagamatsu, Yuiko; Kashiwagi, Hiroko; Yamamuro, Miho; Ishiura, Yoshihito; Ogitani, Ayako; Seino, Yoshiki

    2017-07-01

    The objective of this study was to evaluate the gain in final height of achondroplasia (ACH) patients with long-term growth hormone (GH) treatment. We analyzed medical data of 22 adult patients (8 males and 14 females) treated with GH at a dose of 0.05 mg/kg/day. Optionally, tibial lengthening (TL) was performed with the Ilizalov method in 15 patients and TL as well as femoral lengthening (FL) in 6 patients. Concomitant gonadal suppression therapy with buserelin acetate was applied in 13 patients. The mean treatment periods with GH were 10.7 ± 4.0 and 9.3 ± 2.5 years for males and females, respectively. GH treatment augmented the final height +0.60 ± 0.52 SD (+3.5 cm) and +0.51 ± 1.29 SD (+2.8 cm) in males and females compared to non-treated ACH patients, respectively. Final height of ACH patients that underwent GH and TL increased +1.72 ± 0.72 SD (+10.0 cm) and +1.95 ± 1.34 SD (+9.8 cm) in males and females, respectively. GH, TL, and FL increased their final height +2.97 SD (+17.2 cm) and +3.41 ± 1.63 SD (+17.3 cm) in males and females, respectively. Gonadal suppression therapy had no impact on final height. Long-term GH treatment contributes to 2.6 and 2.1% of final adult height in male and female ACH patients, respectively.

  11. Meclozine Facilitates Proliferation and Differentiation of Chondrocytes by Attenuating Abnormally Activated FGFR3 Signaling in Achondroplasia

    Science.gov (United States)

    Matsushita, Masaki; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Kaneko, Hiroshi; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2013-01-01

    Achondroplasia (ACH) is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS) cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8) cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP) as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias. PMID:24324705

  12. Callus features of regenerate fracture cases in femoral lengthening in achondroplasia

    Energy Technology Data Exchange (ETDEWEB)

    Devmurari, Kamlesh N.; Song, Hae Ryong; Modi, Hitesh N.; Venkatesh, K.P.; Ju, Kim Seung; Song, Sang Heon [Korea University Medical College, Institute for Rare Diseases and Department of Orthopedic Surgery, Seoul (Korea)

    2010-09-15

    We studied the callus features seen in cases of regenerate fracture in femoral lengthening using a monolateral fixator in achondroplasia to determine whether callus types and shapes can predict the probability of callus fracture. The radiographs of 28 cases of femoral lengthening in 14 patients, 14 cases of callus fracture, and 14 cases without callus fracture were retrospectively analyzed by four observers and classified into different shapes and types in concordance with the Ru Li classification. The average lengthening of 9.4 cm (range 7.5-11.8 cm) was achieved, which was 41% (range 30-55%) of the original length and the average timing of callus fracture was 470 days (range 440-545 days) after surgery in the callus fracture group. While the average lengthening of 9.1 cm (range 8-9.7 cm) was achieved, this was 30% (range 28-32%) of the original length in the group of patients without callus fracture. The callus was atypically shaped, there was a 48% average (range 30-72%) reduction of the callus width compared with the natural width of the femur, and a lucent pathway was present in all cases of regenerate fracture. A lucent pathway was seen in all fracture cases with concave, lateral, and atypical shapes, and there was more than 30% lengthening and 30% reduction of the callus width compared with the natural width of the femur, which are the warning signs for regenerate fractures. These signs help the surgeon to predict the outcome and guide him in planning for any additional interventions. The Ru Li classification is an effective method for the evaluation of the chance of callus fracture. (orig.)

  13. Localisation of the gene for achondroplasia to the telomeric region of chromosome 4p

    Energy Technology Data Exchange (ETDEWEB)

    Stoilov, I.; Velinov, M.; Kilpatrick, M.W. [and others

    1994-09-01

    Achondroplasia (ACH), the most common type of genetic dwarfism, is characterized by a variety of skeletal anomalies including disproportionate short stature and rhizomelic shortening of the extremities. The disorder is inherited as an autosomal dominant trait, with a prevalence of 1-15 per 100,000 live births. The etiology of ACH remains unknown, although evidence points to a defect in the maturation of the chondrocytes in the growth plate of the cartilage. To determine the location of the gene responsible for ACH, a panel of 14 families with a total of 43 meioses was genotyped for 40 polymorphic markers for loci randomly distributed throughout the genome. The first significant positive Lod score was obtained for the locus D4S127 (Zmax=3.65 at {theta}=0.03). A series of 20 markers for chromosome 4p16.3 loci were then used to determine the most likely position of the ACH gene. Two additional loci, D4S412 and IDUA, showed strong linkage to the disease (Zmax=3.34 at {theta}=0.03 and Zmax=3.35 at {theta}=0.0, respectively). Multipoint analysis and direct counting of recombinants places the ACH gene in a 2.5 cM region between the marker D4S43 and the chromosome 4p telomere. No evidence was found for genetic heterogeneity. The ACH region contains a number of genes, including that for the fibroblast growth factor receptor FGFR3, which are being evaluated as candidates for the ACH gene. This identification of tightly linked polymorphic markers, as well as being the first step in the characterization of the ACH gene, offers the possibility of DNA based prenatal diagnosis of this disorder.

  14. Early and late fracture following extensive limb lengthening in patients with achondroplasia and hypochondroplasia.

    Science.gov (United States)

    Kitoh, H; Mishima, K; Matsushita, M; Nishida, Y; Ishiguro, N

    2014-09-01

    Two types of fracture, early and late, have been reported following limb lengthening in patients with achondroplasia (ACH) and hypochondroplasia (HCH). We reviewed 25 patients with these conditions who underwent 72 segmental limb lengthening procedures involving the femur and/or tibia, between 2003 and 2011. Gender, age at surgery, lengthened segment, body mass index, the shape of the callus, the amount and percentage of lengthening and the healing index were evaluated to determine predictive factors for the occurrence of early (within three weeks after removal of the fixation pins) and late fracture (> three weeks after removal of the pins). The Mann‑Whitney U test and Pearson's chi-squared test for univariate analysis and stepwise regression model for multivariate analysis were used to identify the predictive factor for each fracture. Only one patient (two tibiae) was excluded from the analysis due to excessively slow formation of the regenerate, which required supplementary measures. A total of 24 patients with 70 limbs were included in the study. There were 11 early fractures in eight patients. The shape of the callus (lateral or central callus) was the only statistical variable related to the occurrence of early fracture in univariate and multivariate analyses. Late fracture was observed in six limbs and the mean time between removal of the fixation pins and fracture was 18.3 weeks (3.3 to 38.4). Lengthening of the tibia, larger healing index, and lateral or central callus were related to the occurrence of a late fracture in univariate analysis. A multivariate analysis demonstrated that the shape of the callus was the strongest predictor for late fracture (odds ratio: 19.3, 95% confidence interval: 2.91 to 128). Lateral or central callus had a significantly larger risk of fracture than fusiform, cylindrical, or concave callus. Radiological monitoring of the shape of the callus during distraction is important to prevent early and late fracture of lengthened

  15. Maternal administration of meclozine for the treatment of foramen magnum stenosis in transgenic mice with achondroplasia.

    Science.gov (United States)

    Matsushita, Masaki; Mishima, Kenichi; Esaki, Ryusaku; Ishiguro, Naoki; Ohno, Kinji; Kitoh, Hiroshi

    2017-01-01

    OBJECTIVE Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Foramen magnum stenosis (FMS) is one of the serious neurological complications in ACH. Through comprehensive drug screening, the authors identified that meclozine, an over-the-counter drug for motion sickness, inhibited activation of FGFR3 signaling. Oral administration of meclozine to the growing ACH mice promoted longitudinal bone growth, but it did not prevent FMS. In the current study, the authors evaluated the effects of maternal administration of meclozine on FMS in ACH mice. METHODS The area of the foramen magnum was measured in 17-day-old Fgfr3 ach mice and wild-type mice using micro-CT scanning. Meclozine was administered to the pregnant mice carrying Fgfr3 ach offspring from embryonic Day (ED) 14.5 to postnatal Day (PD) 4.5. Spheno-occipital and anterior intraoccipital synchondroses were histologically examined, and the bony bridges were scored on PD 4.5. In wild-type mice, tissue concentrations of meclozine in ED 17.5 fetuses and PD 6.5 pups were investigated. RESULTS The area of the foramen magnum was significantly smaller in 17-day-old Fgfr3 ach mice than in wild-type mice (p < 0.005). There were no bony bridges in the spheno-occipital and anterior intraoccipital synchondroses in wild-type mice, while some of the synchondroses prematurely closed in untreated Fgfr3 ach mice at PD 4.5. The average bony bridge score in the cranial base was 7.053 ± 1.393 in untreated Fgfr3 ach mice and 6.125 ± 2.029 in meclozine-treated Fgfr3 ach mice. The scores were not statistically significant between mice with and those without meclozine treatment (p = 0.12). The average tissue concentration of meclozine was significantly higher (508.88 ± 205.16 ng/g) in PD 6.5 mice than in ED 17.5 mice (56.91 ± 20.05 ng/g) (p < 0.005). CONCLUSIONS Maternal administration of meclozine postponed premature

  16. Direct Assessment of the Effect of the Gly380Arg Achondroplasia Mutation on FGFR3 Dimerization Using Quantitative Imaging FRET

    Science.gov (United States)

    Placone, Jesse; Hristova, Kalina

    2012-01-01

    The Gly380Arg mutation in FGFR3 is the genetic cause for achondroplasia (ACH), the most common form of human dwarfism. The mutation has been proposed to increase FGFR3 dimerization, but the dimerization propensities of wild-type and mutant FGFR3 have not been compared. Here we use quantitative imaging FRET to characterize the dimerization of wild-type FGFR3 and the ACH mutant in plasma membrane-derived vesicles from HEK293T cells. We demonstrate a small, but statistically significant increase in FGFR3 dimerization due to the ACH mutation. The data are consistent with the idea that the ACH mutation causes a structural change which affects both the stability and the activity of FGFR3 dimers in the absence of ligand. PMID:23056398

  17. Direct assessment of the effect of the Gly380Arg achondroplasia mutation on FGFR3 dimerization using quantitative imaging FRET.

    Directory of Open Access Journals (Sweden)

    Jesse Placone

    Full Text Available The Gly380Arg mutation in FGFR3 is the genetic cause for achondroplasia (ACH, the most common form of human dwarfism. The mutation has been proposed to increase FGFR3 dimerization, but the dimerization propensities of wild-type and mutant FGFR3 have not been compared. Here we use quantitative imaging FRET to characterize the dimerization of wild-type FGFR3 and the ACH mutant in plasma membrane-derived vesicles from HEK293T cells. We demonstrate a small, but statistically significant increase in FGFR3 dimerization due to the ACH mutation. The data are consistent with the idea that the ACH mutation causes a structural change which affects both the stability and the activity of FGFR3 dimers in the absence of ligand.

  18. Analysis of callus pattern of tibia lengthening in achondroplasia and a novel method of regeneration assessment using pixel values

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Suryaudai; Song, Hae-Ryong; Venkatesh, K.P.; Modi, Hitesh N.; Jang, Ki-Mo; Kim, Seung J. [Korea University Guro Hospital, Rare Diseases Institute, Department of Orthopedic Surgery, Seoul (Korea); Park, Man Sik [Korea University, Department of Biostatistics, College of Medicine, Seoul (Korea)

    2010-03-15

    To relate morphology of new bone formation to outcome after tibial lengthening performed in patients with achondroplasia. A retrospective analysis of 60 tibial segments in 30 achondroplasia patients was performed. There were 22 female patients and eight male patients, with a mean age of 9.8 years. New bone formation was classified by shape, homogeneity and density. Pixel values in relation to original bone were measured using a picture-archiving communication system (PACS). Clinical outcome was described by the external fixator and maturation indices. Mean lengthening was 9.2 cm (range 3-12.7 cm). The mean external fixator index was 23.4 (range 15.1-50). The mean maturation index was 12.3 days/cm (range 6-40 days/cm). Homogeneous pathways were associated with the best clinical results (fixator index 20.4, maturation index 10.8), followed by heterogeneous pathway (external fixator index 26.5, maturation index 16.8) and radiolucent pathway (fixator index 31.2, maturation index 21.4). Both cylindrical (external fixator index 25.2, maturation index 14.5) and concave (external fixator index 26.6, maturation index 16.3) callus shapes were favourable. Mineralization of new bone became equal to that of normal bone within 16 weeks (mean) for homogeneous pathway, 12 weeks for heterogeneous pathway and 32 weeks for lucent pathway. The type of new bone formation seen on radiographs is related to clinical outcome, with homogeneous pathways being the most favourable ones. (orig.)

  19. Analysis of callus pattern of tibia lengthening in achondroplasia and a novel method of regeneration assessment using pixel values

    International Nuclear Information System (INIS)

    Singh, Suryaudai; Song, Hae-Ryong; Venkatesh, K.P.; Modi, Hitesh N.; Jang, Ki-Mo; Kim, Seung J.; Park, Man Sik

    2010-01-01

    To relate morphology of new bone formation to outcome after tibial lengthening performed in patients with achondroplasia. A retrospective analysis of 60 tibial segments in 30 achondroplasia patients was performed. There were 22 female patients and eight male patients, with a mean age of 9.8 years. New bone formation was classified by shape, homogeneity and density. Pixel values in relation to original bone were measured using a picture-archiving communication system (PACS). Clinical outcome was described by the external fixator and maturation indices. Mean lengthening was 9.2 cm (range 3-12.7 cm). The mean external fixator index was 23.4 (range 15.1-50). The mean maturation index was 12.3 days/cm (range 6-40 days/cm). Homogeneous pathways were associated with the best clinical results (fixator index 20.4, maturation index 10.8), followed by heterogeneous pathway (external fixator index 26.5, maturation index 16.8) and radiolucent pathway (fixator index 31.2, maturation index 21.4). Both cylindrical (external fixator index 25.2, maturation index 14.5) and concave (external fixator index 26.6, maturation index 16.3) callus shapes were favourable. Mineralization of new bone became equal to that of normal bone within 16 weeks (mean) for homogeneous pathway, 12 weeks for heterogeneous pathway and 32 weeks for lucent pathway. The type of new bone formation seen on radiographs is related to clinical outcome, with homogeneous pathways being the most favourable ones. (orig.)

  20. [Living with achondroplasia- how do young persons with disproportional short stature rate their quality of life and which factors are associated with quality of life?].

    Science.gov (United States)

    Rohenkohl, Anja C; Sommer, Rachel; Bestges, Stephanie; Kahrs, Sabine; Klingebiel, Karl-Heinz; Bullinger, Monika; Quitmann, Julia

    2015-11-01

    Presently, little is known aqout the quality of life (QoL) as well as the strengths and difficulties of young people with achondroplasia. This study describes these patient-reported indicators and identifies possible correlates. At the invitation of a patient organization, a total of 89 short-statured patients aged 8 to 28 years and their parents participated in this study. QoL was assessed cross-sectionally with both generic and disease-specific instruments and the Strengths and Difficulties Questionnaire (SDQ) as a brief behavioral screening. In addition to descriptive analyses, patient data were compared with a reference population. Hierarchical regression analyses reflecting sociodemographic, clinical, and psychological variables were conducted to identify correlates of QoL. QoL and the strengths and difficulties of young patients with achondroplasia did not differ substantially from a healthy norm sample. However, the participants reported more behavioral problems and limitations in their physical and social QoL compared to patients with another short stature diagnosis. Strengths and difficulties, height-related beliefs, and social support correlated significantly with QoL. Adding psychological variables to the regression model increased the proportion of variance explained in QoL. Young persons with achondroplasia did not differ in their QoL and strengths and difficulties from healthy controls. Characteristics such as height appear less important for the self-perceived QoL than are strengths and difficulties and protective psychosocia~factors.

  1. Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype

    Science.gov (United States)

    Murakami, Shunichi; Balmes, Gener; McKinney, Sandra; Zhang, Zhaoping; Givol, David; de Crombrugghe, Benoit

    2004-01-01

    We generated transgenic mice that express a constitutively active mutant of MEK1 in chondrocytes. These mice showed a dwarf phenotype similar to achondroplasia, the most common human dwarfism, caused by activating mutations in FGFR3. These mice displayed incomplete hypertrophy of chondrocytes in the growth plates and a general delay in endochondral ossification, whereas chondrocyte proliferation was unaffected. Immunohistochemical analysis of the cranial base in transgenic embryos showed reduced staining for collagen type X and persistent expression of Sox9 in chondrocytes. These observations indicate that the MAPK pathway inhibits hypertrophic differentiation of chondrocytes and negatively regulates bone growth without inhibiting chondrocyte proliferation. Expression of a constitutively active mutant of MEK1 in chondrocytes of Fgfr3-deficient mice inhibited skeletal overgrowth, strongly suggesting that regulation of bone growth by FGFR3 is mediated at least in part by the MAPK pathway. Although loss of Stat1 restored the reduced chondrocyte proliferation in mice expressing an achondroplasia mutant of Fgfr3, it did not rescue the reduced hypertrophic zone, the delay in formation of secondary ossification centers, and the achondroplasia-like phenotype. These observations suggest a model in which Fgfr3 signaling inhibits bone growth by inhibiting chondrocyte differentiation through the MAPK pathway and by inhibiting chondrocyte proliferation through Stat1. PMID:14871928

  2. Identification and in silico characterization of p.G380R substitution in FGFR3, associated with achondroplasia in a non-consanguineous Pakistani family.

    Science.gov (United States)

    Ajmal, Muhammad; Mir, Asif; Shoaib, Muhammad; Malik, Salman Akbar; Nasir, Muhammad

    2017-07-05

    The dimerization efficiency of FGFR3 transmembrane domain plays a critical role in the formation of a normal skeleton through the negative regulation of bone development. Recently, gain-of-function mutations in the transmembrane domain of FGFR3 has been described associated with an aberrant negative regulation, leading to the development of achondroplasia-group disorders, including achondroplasia (ACH), hypochondroplasia (HCH) and thanatophoric dysplasia (TD). Here, we describe a non-consanguineous Pakistani family with achondroplasia to explain hereditary basis of the disease. PCR-based linkage analysis using microsatellite markers was employed to localize the disease gene. Gene specific intronic primers were used to amplify the genomic DNA from all affected as well as phenotypically healthy individuals. Amplified PCR products were then subjected to Sanger sequencing and RFLP analysis to identify a potentially pathogenic mutation. The impact of identified mutation on FGFR3 protein's structure and stability was highlighted through different bioinformatics tools. Genetic screening of the family revealed a previously reported heterozygous c.1138 G > A (p.G380R) mutation in the coding exon 8 of FGFR3 gene. Identified genetic variation was confirmed in all affected individuals while healthy individuals and controls were found genotypically normal. The results were further validated by RFLP analysis as c.1138 G > A substitution generates a unique recognition site for SfcI endonuclease. Following SfcI digestion, the electrophoretic pattern of three bands/DNA fragments for each patient is indicative of heterozygous status of the disease allele. In silico studies of the mutant FGFR3 protein predicted to adversely affect the stability of FGFR3 protein. Mutation in the transmembrane domain may adversely affect the dimerization efficiency and overall stability of the FGFR3, leading to a constitutively active protein. As a result, an uncontrolled intracellular signaling

  3. Long-term follow-up of a child with Klinefelter syndrome and achondroplasia from infancy to 16 years.

    Science.gov (United States)

    Arditi, Jessica D; Thomaidis, Loretta; Frysira, Helen; Doulgeraki, Artemis; Chrousos, George P; Kanaka-Gantenbein, Christina

    2017-07-26

    Achondroplasia (ACH), an autosomal dominant skeletal dysplasia, occurs in approximately 1:20,000 births. On the other hand, 47,XXY aneuploidy (Klinefelter syndrome [KS]) is the most common sex chromosome disorder, with a prevalence of approximately 1:600 males. To the best of our knowledge, only five cases of patients presenting both ACH and KS have been reported to date in the international literature. However, none of these cases has been longitudinally followed during the entire childhood. We report a male patient with ACH and KS, diagnosed in early infancy because of his typical phenotype of ACH. The diagnosis was confirmed by molecular analysis revealing a de novo heterozygous 1138 G-to-A mutation of the FGFR3 gene. During his first assessment, a karyotype was performed, which also revealed coexistence of KS. He was followed by our pediatric endocrinology team until the age of 16 years, then he was gradually transferred to adult endocrine care. This is the first reported case with both conditions that was diagnosed in infancy and was longitudinally followed by a pediatric endocrinology team regularly, from infancy to late adolescence. With a typical phenotype of ACH, it is striking and noteworthy that he did not develop the classical endocrine complications of a child with KS, neither did he necessitate testosterone supplementation during his pubertal development, due to his normal virilization and testosterone levels.

  4. Meckel’s and condylar cartilages anomalies in achondroplasia result in defective development and growth of the mandible

    Science.gov (United States)

    Biosse Duplan, Martin; Komla-Ebri, Davide; Heuzé, Yann; Estibals, Valentin; Gaudas, Emilie; Kaci, Nabil; Benoist-Lasselin, Catherine; Zerah, Michel; Kramer, Ina; Kneissel, Michaela; Porta, Diana Grauss; Di Rocco, Federico; Legeai-Mallet, Laurence

    2016-01-01

    Activating FGFR3 mutations in human result in achondroplasia (ACH), the most frequent form of dwarfism, where cartilages are severely disturbed causing long bones, cranial base and vertebrae defects. Because mandibular development and growth rely on cartilages that guide or directly participate to the ossification process, we investigated the impact of FGFR3 mutations on mandibular shape, size and position. By using CT scan imaging of ACH children and by analyzing Fgfr3Y367C/+ mice, a model of ACH, we show that FGFR3 gain-of-function mutations lead to structural anomalies of primary (Meckel’s) and secondary (condylar) cartilages of the mandible, resulting in mandibular hypoplasia and dysmorphogenesis. These defects are likely related to a defective chondrocyte proliferation and differentiation and pan-FGFR tyrosine kinase inhibitor NVP-BGJ398 corrects Meckel’s and condylar cartilages defects ex vivo. Moreover, we show that low dose of NVP-BGJ398 improves in vivo condyle growth and corrects dysmorphologies in Fgfr3Y367C/+ mice, suggesting that postnatal treatment with NVP-BGJ398 mice might offer a new therapeutic strategy to improve mandible anomalies in ACH and others FGFR3-related disorders. PMID:27260401

  5. Lower limb lengthening in patients with disproportionate short stature with achondroplasia: a systematic review of the last 20 years.

    Science.gov (United States)

    Schiedel, Frank; Rödl, Robert

    2012-01-01

    Parents of children suffering from disproportionate short stature due to achondroplasia may wish to have surgical leg lengthening carried out for the child. The aim is not to increase height, but rather to achieve physiological proportions in the body. In a systematic review of the literature on the topic dating from the last 20 years, the surgical approaches used for this purpose were analyzed in accordance with the Preferred reporting items for systematic reviews and meta-analyses (PRISMA) criteria. Twelve studies show that to date, involvement of the child in decision-making at the start of treatment has been expected and that it is recommended from the age of 12. In highly heterogeneous patient groups, with varying factors involved and different techniques being used, lengthening (often by more than 10 cm) is described. High complication rates are reported, with many setbacks often requiring repeat surgery. Using PALEY'S multiplier method, the expected standing height, sitting height, and leg length can be predicted and an individualized treatment approach can be planned and operative procedures could be started in early childhood as PERETTI suggests. As the patients are unable to be involved in decision-making as young children, these data may provide a basis for offering differentiated advice to parents, who usually consult a pediatric orthopedist at a very early stage in the child's life.

  6. Dynamic cervicomedullary cord compression and alterations in cerebrospinal fluid dynamics in children with achondroplasia: review of an 11-year surgical case series.

    Science.gov (United States)

    Mukherjee, Debraj; Pressman, Barry D; Krakow, Deborah; Rimoin, David L; Danielpour, Moise

    2014-09-01

    Achondroplasia may be associated with compression at the cervicomedullary junction. Determining which patients are at greatest risk for neurological complications of cervicomedullary compression can be difficult. In the current study the authors reviewed their records to determine the incidence and clinical significance of dynamic cervicomedullary stenosis and obstruction of CSF flow along with surgical outcomes following posterior fossa decompression. The authors reviewed 34 consecutive cases involving symptomatic children with achondroplasia undergoing cervicomedullary decompression performed by a single surgeon over 11 years. Of these patients, 29 had undergone preoperative dynamic MRI of the cervicomedullary junction with cine (cinema) CSF flow studies; 13 of these patients underwent postoperative dynamic MRI studies. Clinical outcomes included changes in polysomnography, head circumference percentile, and fontanel characteristics. Radiographic outcomes included changes in dynamic spinal cord diameter, improvement in CSF flow at the foramen magnum, and change in the Evans ratio. Patients were predominantly female, with a mean age at presentation of 6.6 years and mean follow-up of 3.7 years (range 1-10 years). All patients had moderate to excellent improvement in postoperative polysomnography, slight decrease in average head circumference percentile (from 46.9th percentile to 45.7th percentile), and no subjective worsening of fontanel characteristics. The Evans ratio decreased by 2%, spinal cord diameter increased an average of 3.1 mm, 5.2 mm, and 0.2 mm in the neutral, flexed, and extended positions, respectively, and CSF flow improved qualitatively in all 3 positions. There were no postoperative infections, CSF leaks, or other major complications. None of the patients undergoing initial foramen magnum decompression performed at our medical center required reoperation. Patients with achondroplasia and symptomatic cervicomedullary compression have increased risk

  7. Myelography in achondroplasia: value of a lateral C1-2 puncture and non-ionic, water-soluble contrast medium

    International Nuclear Information System (INIS)

    Suss, R.A.; Udvarhelyi, G.B.; Wang, H.; Kumar, A.J.; Zinreich, S.J.; Rosenbaum, A.E.

    1983-01-01

    Because of technical difficulties and diagnostic limitations encountered with other myelographic techniques in patients with achondroplasia, the authors employed a lateral C1-2 puncture and non-ionic, water-soluble contrast medium in 18 achondroplastic patients with spinal compression (21 procedures). This technique proved most appropriate for identifying the upper limit of degenerative osteophytes causing exacerbation of congenital spinal stenosis, which is crucial in planning decompressive surgery. A potentially important additional finding was the presence of degenerative lower cervical spine disease in the majority of patients. There were no serious complications. The authors recommend this technique as safe and effective in achondroplastic patients with severe congenital spinal stenosis

  8. Effect of the achondroplasia mutation on FGFR3 dimerization and FGFR3 structural response to fgf1 and fgf2: A quantitative FRET study in osmotically derived plasma membrane vesicles.

    Science.gov (United States)

    Sarabipour, Sarvenaz; Hristova, Kalina

    2016-07-01

    The G380R mutation in the transmembrane domain of FGFR3 is a germline mutation responsible for most cases of Achondroplasia, a common form of human dwarfism. Here we use quantitative Fӧster Resonance Energy Transfer (FRET) and osmotically derived plasma membrane vesicles to study the effect of the achondroplasia mutation on the early stages of FGFR3 signaling in response to the ligands fgf1 and fgf2. Using a methodology that allows us to capture structural changes on the cytoplasmic side of the membrane in response to ligand binding to the extracellular domain of FGFR3, we observe no measurable effects of the G380R mutation on FGFR3 ligand-bound dimer configurations. Instead, the most notable effect of the achondroplasia mutation is increased propensity for FGFR3 dimerization in the absence of ligand. This work reveals new information about the molecular events that underlie the achondroplasia phenotype, and highlights differences in FGFR3 activation due to different single amino-acid pathogenic mutations. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. New aids for the non-invasive prenatal diagnosis of achondroplasia: dysmorphic features, charts of fetal size and molecular confirmation using cell-free fetal DNA in maternal plasma

    NARCIS (Netherlands)

    Chitty, L. S.; Griffin, D. R.; Meaney, C.; Barrett, A.; Khalil, A.; Pajkrt, E.; Cole, T. J.

    2011-01-01

    To improve the prenatal diagnosis of achondroplasia by constructing charts of fetal size, defining frequency of sonographic features and exploring the role of non-invasive molecular diagnosis based on cell-free fetal deoxyribonucleic acid (DNA) in maternal plasma. Data on fetuses with a confirmed

  10. Serum NT-proCNP levels increased after initiation of GH treatment in patients with achondroplasia/hypochondroplasia.

    Science.gov (United States)

    Kubota, Takuo; Wang, Wei; Miura, Kohji; Nakayama, Hirofumi; Yamamoto, Keiko; Fujiwara, Makoto; Ohata, Yasuhisa; Tachibana, Makiko; Kitaoka, Taichi; Takakuwa, Satoshi; Miyoshi, Yoko; Namba, Noriyuki; Ozono, Keiichi

    2016-06-01

    Serum amino-terminal propeptide of C-type natriuretic peptide (NT-proCNP) levels have been proposed as a biomarker of linear growth in healthy children. The usefulness of NT-proCNP in patients with achondroplasia (ACH)/hypochondroplasia (HCH) remains to be elucidated. The objective was to study whether serum NT-proCNP level is a good biomarker for growth in ACH/HCH and other patients of short stature. This was a longitudinal cohort study. Sixteen children with ACH (aged 0·4-4·3 years), six children with HCH (2·7-6·3 years), 23 children with idiopathic short stature (ISS) (2·2-9·0 years), eight short children with GH deficiency (GHD) (2·9-6·8 years) and five short children born small for gestational age (SGA) (2·0-6·6 years). Patients with ACH/HCH received GH treatment for 1 year. Serum NT-proCNP levels and height were measured. NT-proCNP levels positively correlated with height velocity in these short children (P < 0·05, r = 0·27). NT-proCNP levels inversely correlated with age in children with ISS alone (P < 0·01, r = -0·55). Serum NT-proCNP levels in patients with ACH/HCH were increased 3 months following the initiation of GH treatment (P < 0·05). Height SDS gain during GH treatment for 1 year was positively correlated with the changes in NT-proCNP levels after the initiation of GH (P < 0·01, r = 0·72). Serum NT-proCNP levels may be a good biomarker to indicate the effect of GH treatment on growth in patients with ACH/HCH at least in the first year and height velocity in short stature patients. © 2016 John Wiley & Sons Ltd.

  11. New aids for the non-invasive prenatal diagnosis of achondroplasia: dysmorphic features, charts of fetal size and molecular confirmation using cell-free fetal DNA in maternal plasma.

    Science.gov (United States)

    Chitty, L S; Griffin, D R; Meaney, C; Barrett, A; Khalil, A; Pajkrt, E; Cole, T J

    2011-03-01

    To improve the prenatal diagnosis of achondroplasia by constructing charts of fetal size, defining frequency of sonographic features and exploring the role of non-invasive molecular diagnosis based on cell-free fetal deoxyribonucleic acid (DNA) in maternal plasma. Data on fetuses with a confirmed diagnosis of achondroplasia were obtained from our databases, records reviewed, sonographic features and measurements determined and charts of fetal size constructed using the LMS (lambda-mu-sigma) method and compared with charts used in normal pregnancies. Cases referred to our regional genetics laboratory for molecular diagnosis using cell-free fetal DNA were identified and results reviewed. Twenty-six cases were scanned in our unit. Fetal size charts showed that femur length was usually on or below the 3(rd) centile by 25 weeks' gestation, and always below the 3(rd) by 30 weeks. Head circumference was above the 50(th) centile, increasing to above the 95(th) when compared with normal for the majority of fetuses. The abdominal circumference was also increased but to a lesser extent. Commonly reported sonographic features were bowing of the femora, frontal bossing, short fingers, a small chest and polyhydramnios. Analysis of cell-free fetal DNA in six pregnancies confirmed the presence of the c.1138G > A mutation in the FGRF3 gene in four cases with achondroplasia, but not the two subsequently found to be growth restricted. These data should improve the accuracy of diagnosis of achondroplasia based on sonographic findings, and have implications for targeted molecular confirmation that can reliably and safely be carried out using cell-free fetal DNA. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

  12. Limb lengthening in achondroplasia

    Directory of Open Access Journals (Sweden)

    Sanjay K Chilbule

    2016-01-01

    Full Text Available Background: Stature lengthening in skeletal dysplasia is a contentious issue. Specific guidelines regarding the age and sequence of surgery, methods and extent of lengthening at each stage are not uniform around the world. Despite the need for multiple surgeries, with their attendant complications, parents demanding stature lengthening are not rare, due to the social bias and psychological effects experienced by these patients. This study describes the outcome and complications of extensive stature lengthening performed at our center. Materials and Methods: Eight achondroplasic and one hypochondroplasic patient underwent bilateral transverse lengthening for tibiae, humeri and femora. Tibia lengthening was carried out using a ring fixator and bifocal corticotomy, while a monolateral pediatric limb reconstruction system with unifocal corticotomy was used for the femur and humerus. Lengthening of each bone segment, height gain, healing index and complications were assessed. Subgroup analysis was carried out to assess the effect of age and bone segment on the healing index. Results: Nine patients aged five to 25 years (mean age 10.2 years underwent limb lengthening procedures for 18 tibiae, 10 femora and 8 humeri. Four patients underwent bilateral lengthening of all three segments. The mean length gain for the tibia, femur and humerus was 15.4 cm (100.7%, 9.9 cm (52.8% and 9.6 cm (77.9%, respectively. Healing index was 25.7, 25.6 and 20.6 days/cm, respectively, for the tibia, femur and humerus. An average of 33.3% height gain was attained. Lengthening of both tibia and femur added to projected height achieved as the 3 rd percentile of standard height in three out of four patients. In all, 33 complications were encountered (0.9 complications per segment. Healing index was not affected by age or bone segment. Conclusion: Extensive limb lengthening (more than 50% over initial length carries significant risk and should be undertaken only after due consideration.

  13. Limb lengthening in achondroplasia

    OpenAIRE

    Chilbule, Sanjay K; Dutt, Vivek; Madhuri, Vrisha

    2016-01-01

    Background: Stature lengthening in skeletal dysplasia is a contentious issue. Specific guidelines regarding the age and sequence of surgery, methods and extent of lengthening at each stage are not uniform around the world. Despite the need for multiple surgeries, with their attendant complications, parents demanding stature lengthening are not rare, due to the social bias and psychological effects experienced by these patients. This study describes the outcome and complications of extensive s...

  14. Limb lengthening in achondroplasia.

    Science.gov (United States)

    Chilbule, Sanjay K; Dutt, Vivek; Madhuri, Vrisha

    2016-01-01

    Stature lengthening in skeletal dysplasia is a contentious issue. Specific guidelines regarding the age and sequence of surgery, methods and extent of lengthening at each stage are not uniform around the world. Despite the need for multiple surgeries, with their attendant complications, parents demanding stature lengthening are not rare, due to the social bias and psychological effects experienced by these patients. This study describes the outcome and complications of extensive stature lengthening performed at our center. Eight achondroplasic and one hypochondroplasic patient underwent bilateral transverse lengthening for tibiae, humeri and femora. Tibia lengthening was carried out using a ring fixator and bifocal corticotomy, while a monolateral pediatric limb reconstruction system with unifocal corticotomy was used for the femur and humerus. Lengthening of each bone segment, height gain, healing index and complications were assessed. Subgroup analysis was carried out to assess the effect of age and bone segment on the healing index. Nine patients aged five to 25 years (mean age 10.2 years) underwent limb lengthening procedures for 18 tibiae, 10 femora and 8 humeri. Four patients underwent bilateral lengthening of all three segments. The mean length gain for the tibia, femur and humerus was 15.4 cm (100.7%), 9.9 cm (52.8%) and 9.6 cm (77.9%), respectively. Healing index was 25.7, 25.6 and 20.6 days/cm, respectively, for the tibia, femur and humerus. An average of 33.3% height gain was attained. Lengthening of both tibia and femur added to projected height achieved as the 3(rd) percentile of standard height in three out of four patients. In all, 33 complications were encountered (0.9 complications per segment). Healing index was not affected by age or bone segment. Extensive limb lengthening (more than 50% over initial length) carries significant risk and should be undertaken only after due consideration.

  15. Non-invasive prenatal diagnosis of achondroplasia and thanatophoric dysplasia: next-generation sequencing allows for a safer, more accurate, and comprehensive approach.

    Science.gov (United States)

    Chitty, Lyn S; Mason, Sarah; Barrett, Angela N; McKay, Fiona; Lench, Nicholas; Daley, Rebecca; Jenkins, Lucy A

    2015-07-01

    Accurate prenatal diagnosis of genetic conditions can be challenging and usually requires invasive testing. Here, we demonstrate the potential of next-generation sequencing (NGS) for the analysis of cell-free DNA in maternal blood to transform prenatal diagnosis of monogenic disorders. Analysis of cell-free DNA using a PCR and restriction enzyme digest (PCR-RED) was compared with a novel NGS assay in pregnancies at risk of achondroplasia and thanatophoric dysplasia. PCR-RED was performed in 72 cases and was correct in 88.6%, inconclusive in 7% with one false negative. NGS was performed in 47 cases and was accurate in 96.2% with no inconclusives. Both approaches were used in 27 cases, with NGS giving the correct result in the two cases inconclusive with PCR-RED. NGS provides an accurate, flexible approach to non-invasive prenatal diagnosis of de novo and paternally inherited mutations. It is more sensitive than PCR-RED and is ideal when screening a gene with multiple potential pathogenic mutations. These findings highlight the value of NGS in the development of non-invasive prenatal diagnosis for other monogenic disorders. © 2015 John Wiley & Sons, Ltd.

  16. A novel non-invasive detection method for the FGFR3 gene mutation in maternal plasma for a fetal achondroplasia diagnosis based on signal amplification by hemin-MOFs/PtNPs.

    Science.gov (United States)

    Chen, Jun; Yu, Chao; Zhao, Yilin; Niu, Yazhen; Zhang, Lei; Yu, Yujie; Wu, Jing; He, Junlin

    2017-05-15

    The small amount of cell-free fetal DNA (cffDNA) can be a useful biomarker for early non-invasive prenatal diagnosis (NIPD) of achondroplasia. In this study, a novel non-invasive electrochemical DNA sensor for ultrasensitive detecting FGFR3 mutation gene, a pathogenic gene of achondroplasia, based on biocatalytic signal materials and the biotin-streptavidin system are presented. Notably encapsulation of hemin in metal-organic frameworks-based materials (hemin-MOFs) and platinum nanoparticles (PtNPs) were used to prepare hemin-MOFs/PtNPs composites via a one-beaker-one-step reduction. We utilized hemin-MOFs/PtNPs for signal amplification because the promising hemin-MOFs/PtNPs nanomaterial has remarkable ability of catalyze H 2 O 2 as well as excellent conductivity. To further amplify the electrochemical signal, reduced graphene oxide-tetraethylene pentamine (rGO-TEPA), gold nanoparticles and streptavidin were selected for modification of the electrode to enhance the conductivity and immobilize more biotin-modified capture probe (Bio-CP) through the high specificity and superior affinity between streptavidin and biotin. The electrochemical signal was primarily derived from the synergistic catalysis of H 2 O 2 by hemin and PtNPs and recorded by Chronoamperometry. Under the optimal conditions, this newly designed biosensor exhibited sensitive detection of FGFR3 from 0.1fM to 1nM with a low detection limit of 0.033fM (S/N=3). We proposed that this ultrasensitive biosensor is useful for the early non-invasive prenatal diagnosis of achondroplasia. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Meclozine promotes longitudinal skeletal growth in transgenic mice with achondroplasia carrying a gain-of-function mutation in the FGFR3 gene.

    Science.gov (United States)

    Matsushita, Masaki; Hasegawa, Satoru; Kitoh, Hiroshi; Mori, Kensaku; Ohkawara, Bisei; Yasoda, Akihiro; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2015-02-01

    Achondroplasia (ACH) is one of the most common skeletal dysplasias causing short stature owing to a gain-of-function mutation in the FGFR3 gene, which encodes the fibroblast growth factor receptor 3. We found that meclozine, an over-the-counter drug for motion sickness, inhibited elevated FGFR3 signaling in chondrocytic cells. To examine the feasibility of meclozine administration in clinical settings, we investigated the effects of meclozine on ACH model mice carrying the heterozygous Fgfr3(ach) transgene. We quantified the effect of meclozine in bone explant cultures employing limb rudiments isolated from developing embryonic tibiae from Fgfr3(ach) mice. We found that meclozine significantly increased the full-length and cartilaginous primordia of embryonic tibiae isolated from Fgfr3(ach) mice. We next analyzed the skeletal phenotypes of growing Fgfr3(ach) mice and wild-type mice with or without meclozine treatment. In Fgfr3(ach) mice, meclozine significantly increased the body length after 2 weeks of administration. At skeletal maturity, the bone lengths including the cranium, radius, ulna, femur, tibia, and vertebrae were significantly longer in meclozine-treated Fgfr3(ach) mice than in untreated Fgfr3(ach) mice. Interestingly, meclozine also increased bone growth in wild-type mice. The plasma concentration of meclozine during treatment was within the range that has been used in clinical settings for motion sickness. Increased longitudinal bone growth in Fgfr3(ach) mice by oral administration of meclozine in a growth period suggests potential clinical feasibility of meclozine for the improvement of short stature in ACH.

  18. The Oxygen Consumption and Metabolic Cost of Walking and Running in Adults With Achondroplasia

    Directory of Open Access Journals (Sweden)

    David T. Sims

    2018-04-01

    Full Text Available The disproportionate body mass and leg length of Achondroplasic individuals may affect their net oxygen consumption (V͘O2 and metabolic cost (C when walking at running compared to those of average stature (controls. The aim of this study was to measure submaximal V͘O2 and C during a range of set walking speeds (SWS; 0.56 – 1.94 m⋅s-1, increment 0.28 m⋅s-1, set running speeds (SRS; 1.67 – 3.33 m⋅s-1, increment 0.28 m⋅s-1 and a self-selected walking speed (SSW. V͘O2 and C was scaled to total body mass (TBM and fat free mass (FFM while gait speed was scaled to leg length using Froude’s number (Fr. Achondroplasic V͘O2TBM and V͘O2FFM were on average 29 and 35% greater during SWS (P < 0.05 and 12 and 18% higher during SRS (P < 0.05 than controls, respectively. Achondroplasic CTBM and CFFM were 29 and 33% greater during SWS (P < 0.05 and 12 and 18% greater during SRS (P < 0.05 than controls, respectively. There was no difference in SSW V͘O2TBM or V͘O2FFM between groups (P > 0.05, but CTBM and CFFM at SSW were 23 and 29% higher (P < 0.05 in the Achondroplasic group compared to controls, respectively. V͘O2TBM and V͘O2FFM correlated with Fr for both groups (r = 0.984 – 0.999, P < 0.05. Leg length accounted for the majority of the higher V͘O2TBM and V͘O2FFM in the Achondroplasic group, but further work is required to explain the higher Achondroplasic CTBM and CFFM at all speeds compared to controls.New and Noteworthy: There is a leftward shift of oxygen consumption scaled to total body mass and fat free mass in Achondroplasic adults when walking and running. This is nullified when talking into account leg length. However, despite these scalars, Achondroplasic individuals have a higher walking and metabolic cost compared to age matched non-Achondroplasic individuals, suggesting biomechanical differences between the groups.

  19. Quantitative approach to the posterior cranial fossa and craniocervical junction in asymptomatic children with achondroplasia

    International Nuclear Information System (INIS)

    Calandrelli, Rosalinda; Panfili, Marco; D'Apolito, Gabriella; Pedicelli, Alessandro; Colosimo, Cesare; Zampino, Giuseppe; Pilato, Fabio

    2017-01-01

    We propose an magnetic resonance imaging (MRI)-based quantitative morphovolumetric approach to the posterior cranial fossa (PCF) and craniocervical junction (CCJ) changes in achondroplastic patients investigating possible associations with ventriculomegaly and medullary compression. We analyzed MRI of 13 achondroplastic children not treated by surgery. 3D FSPGR T1-weighted images were used to analyze (1) PCF synchondroses; (2) PCF volume (PCFV), PCF brain volume (PCFBV), PCFV/PCFBV ratio, cerebellar volume, cerebrospinal fluid (CSF) spaces volume, and IV ventricle volume; (3) PCF (clivus, supraocciput, exocciput lengths, tentorial angle) and CCJ (AP and LL diameters of foramen magnum (FM)) morphometry; (4) measurements of FM and jugular foramina (JF) areas; and (5) supratentorial ventricular volume. All patients showed synostosis of spheno-occipital synchondroses, eight showed synostosis of intra-occipital synchondroses, nine showed CCJ impingement on the cervical cord but only three had cervical myelopathy. Compared to controls, clivus and exocciput lengths, LL and AP diameters of FM, FM area and JF area were significantly reduced, supraocciput length, tentorial angle, PCFV, PCFBV, cerebellar volume, supratentorial ventricular system volume were significantly increased. A correlation was found between clivus length and supratentorial ventricular volume, premature closure of intra-occipital synchondroses and FM area while a trend was found between FM area and supraocciput length. Our analysis demonstrates a relationship between the shortening of the clivus and the ventriculomegaly. On the other hand the premature closure of PCF synchondroses, the shape, and the growth direction of supraocciput bone contribute to reduce the FM area, causing in some patients medullary compression. (orig.)

  20. Cervical high-intensity intramedullary lesions in achondroplasia : Aetiology, prevalence and clinical relevance

    NARCIS (Netherlands)

    Brouwer, Patrick A.; Lubout, Charlotte M.; van Dijk, J. Marc C.; Vleggeert-Lankamp, Carmen L.

    2012-01-01

    In achondroplastic patients with slight complaints of medullary compression the cervical spinal cord regularly exhibits an intramedullary (CHII) lesion just below the craniocervical junction with no signs of focal compression on the cord. Currently, the prevalence of the lesion in the general

  1. Quantitative approach to the posterior cranial fossa and craniocervical junction in asymptomatic children with achondroplasia

    Energy Technology Data Exchange (ETDEWEB)

    Calandrelli, Rosalinda; Panfili, Marco; D' Apolito, Gabriella; Pedicelli, Alessandro; Colosimo, Cesare [Fondazione Policlinico Universitario Agostino Gemelli, Univ. Cattolica del Sacro Cuore, Area Diagnostica per Immagini, Roma (Italy); Zampino, Giuseppe [Fondazione Policlinico Universitario Agostino Gemelli, Univ. Cattolica del Sacro Cuore, Area Salute del Bambino, Roma (Italy); Pilato, Fabio [Fondazione Policlinico Universitario Agostino Gemelli, Univ. Cattolica del Sacro Cuore, Area Neuroscienze, Roma (Italy)

    2017-10-15

    We propose an magnetic resonance imaging (MRI)-based quantitative morphovolumetric approach to the posterior cranial fossa (PCF) and craniocervical junction (CCJ) changes in achondroplastic patients investigating possible associations with ventriculomegaly and medullary compression. We analyzed MRI of 13 achondroplastic children not treated by surgery. 3D FSPGR T1-weighted images were used to analyze (1) PCF synchondroses; (2) PCF volume (PCFV), PCF brain volume (PCFBV), PCFV/PCFBV ratio, cerebellar volume, cerebrospinal fluid (CSF) spaces volume, and IV ventricle volume; (3) PCF (clivus, supraocciput, exocciput lengths, tentorial angle) and CCJ (AP and LL diameters of foramen magnum (FM)) morphometry; (4) measurements of FM and jugular foramina (JF) areas; and (5) supratentorial ventricular volume. All patients showed synostosis of spheno-occipital synchondroses, eight showed synostosis of intra-occipital synchondroses, nine showed CCJ impingement on the cervical cord but only three had cervical myelopathy. Compared to controls, clivus and exocciput lengths, LL and AP diameters of FM, FM area and JF area were significantly reduced, supraocciput length, tentorial angle, PCFV, PCFBV, cerebellar volume, supratentorial ventricular system volume were significantly increased. A correlation was found between clivus length and supratentorial ventricular volume, premature closure of intra-occipital synchondroses and FM area while a trend was found between FM area and supraocciput length. Our analysis demonstrates a relationship between the shortening of the clivus and the ventriculomegaly. On the other hand the premature closure of PCF synchondroses, the shape, and the growth direction of supraocciput bone contribute to reduce the FM area, causing in some patients medullary compression. (orig.)

  2. The Oxygen Consumption and Metabolic Cost of Walking and Running in Adults With Achondroplasia

    Science.gov (United States)

    Sims, David T.; Onambélé-Pearson, Gladys L.; Burden, Adrian; Payton, Carl; Morse, Christopher I.

    2018-01-01

    The disproportionate body mass and leg length of Achondroplasic individuals may affect their net oxygen consumption (V͘O2) and metabolic cost (C) when walking at running compared to those of average stature (controls). The aim of this study was to measure submaximal V͘O2 and C during a range of set walking speeds (SWS; 0.56 – 1.94 m⋅s-1, increment 0.28 m⋅s-1), set running speeds (SRS; 1.67 – 3.33 m⋅s-1, increment 0.28 m⋅s-1) and a self-selected walking speed (SSW). V͘O2 and C was scaled to total body mass (TBM) and fat free mass (FFM) while gait speed was scaled to leg length using Froude’s number (Fr). Achondroplasic V͘O2TBM and V͘O2FFM were on average 29 and 35% greater during SWS (P 0.05), but CTBM and CFFM at SSW were 23 and 29% higher (P < 0.05) in the Achondroplasic group compared to controls, respectively. V͘O2TBM and V͘O2FFM correlated with Fr for both groups (r = 0.984 – 0.999, P < 0.05). Leg length accounted for the majority of the higher V͘O2TBM and V͘O2FFM in the Achondroplasic group, but further work is required to explain the higher Achondroplasic CTBM and CFFM at all speeds compared to controls. New and Noteworthy: There is a leftward shift of oxygen consumption scaled to total body mass and fat free mass in Achondroplasic adults when walking and running. This is nullified when talking into account leg length. However, despite these scalars, Achondroplasic individuals have a higher walking and metabolic cost compared to age matched non-Achondroplasic individuals, suggesting biomechanical differences between the groups. PMID:29720948

  3. The prevalence of the complications and their associated factors in humeral lengthening for achondroplasia: retrospective study of 54 cases.

    Science.gov (United States)

    Nakano-Matsuoka, Natsuko; Fukiage, Kenichi; Harada, Yuki; Kashiwagi, Naoya; Futami, Tohru

    2017-11-01

    The aim of this study is to evaluate the complications of humeral lengthening and their associated factors. Fifty-four achondroplastic patients were treated by bilateral humeral lengthening. Our original shoulder sling was sufficient to prevent shoulder dislocation. Pre-existing radial head dislocation was observed in 18 patients. Lengthening was accomplished in all cases without a decrease in the elbow function. Seven humeri fractured after the fixator removal. The risk factors for postoperative fracture were a waiting period of less than 5 days, a healing index less than 25, and the concave shape of the callus. There was no radial nerve palsy.

  4. HDAC6 deficiency or inhibition blocks FGFR3 accumulation and improves bone growth in a model of achondroplasia.

    Science.gov (United States)

    Ota, Sara; Zhou, Zi-Qiang; Romero, Megan P; Yang, Guang; Hurlin, Peter J

    2016-10-01

    Mutations that cause increased and/or inappropriate activation of FGFR3 are responsible for a collection of short-limbed chondrodysplasias. These mutations can alter receptor trafficking and enhance receptor stability, leading to increased receptor accumulation and activity. Here, we show that wildtype and mutant activated forms of FGFR3 increase expression of the cytoplasmic deacetylase HDAC6 (Histone Deacetylase 6) and that FGFR3 accumulation is compromised in cells lacking HDAC6 or following treatment of fibroblasts or chondrocytes with small molecule inhibitors of HDAC6. The reduced accumulation of FGFR3 was linked to increased FGFR3 degradation that occurred through a lysosome-dependent mechanism. Using a mouse model of Thanatophoric Dysplasia Type II (TDII) we show that both HDAC6 deletion and treatment with the small molecule HDAC6 inhibitor tubacin reduced FGFR3 accumulation in the growth plate and improved endochondral bone growth. Defective endochondral growth in TDII is associated with reduced proliferation and poor hypertrophic differentiation and the improved bone growth was associated with increased chondrocyte proliferation and expansion of the differentiation compartment within the growth plate. These findings further define the mechanisms that control FGFR3 accumulation and contribute to skeletal pathology caused by mutations in FGFR3. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Genetics Home Reference: thanatophoric dysplasia

    Science.gov (United States)

    ... thanatophoric dysplasia and their potential therapeutic implications for achondroplasia. Am J Med Genet A. 2010 Jan;152A( ... of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon ...

  6. Genetics Home Reference: SADDAN

    Science.gov (United States)

    ... view the expand/collapse boxes. Description SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a ... Genetic Testing (1 link) Genetic Testing Registry: Severe achondroplasia with developmental delay and acanthosis nigricans Other Diagnosis ...

  7. Lordosis - lumbar

    Science.gov (United States)

    ... spine. Much less common causes in children include: Achondroplasia , a disorder of bone growth that causes the ... Carson BS, Rigamonti D, Ahn ES. Achondroplasia and other dwarfisms. ... PA: Elsevier Saunders; 2011:chap 219. Mistovich RJ, Spiegel ...

  8. Genetics Home Reference: Crouzon syndrome with acanthosis nigricans

    Science.gov (United States)

    ... Neidich JA, Wilcox WR. Subtle radiographic findings of achondroplasia in patients with Crouzon syndrome with acanthosis nigricans ... of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon ...

  9. Radiographic manifestations of hypochondroplasia

    Energy Technology Data Exchange (ETDEWEB)

    Heselson, N G; Cremin, B J [Groote Schuur Hospital, Cape Town (South Africa); Beighton, P

    1979-01-01

    Hypochrondroplasia is an inherited skeletal dysplasia that resembles achondroplasia in mild degree. Radiographic manifestations encountered in 12 affected individuals in South Africa include slight shortening of all segments of the tubular bones, moderate caudal diminution of the lumbar interpedicular distances, increased lumbar lordosis with cacral tilt and distal prolongation of the fibular. Hypochondroplasia can be distinguished from other osteochondrodystrophies such as achondroplasia, pseudo-achondroplasia and metaphyseal chondroplasia by the recognition of it clinical and radiographic manifestations.

  10. The radiographic manifestations of hypochondroplasia

    International Nuclear Information System (INIS)

    Heselson, N.G.; Cremin, B.J.; Beighton, P.

    1979-01-01

    Hypochrondroplasia is an inherited skeletal dysplasia that resembles achondroplasia in mild degree. Radiographic manifestations encountered in 12 affected individuals in South Africa include slight shortening of all segments of the tubular bones, moderate caudal diminution of the lumbar interpedicular distances, increased lumbar lordosis with cacral tilt and distal prolongation of the fibular. Hypochondroplasia can be distinguished from other osteochondrodystrophies such as achondroplasia, pseudo-achondroplasia and metaphyseal chondroplasia by the recognition of it clinical and radiographic manifestations. (author)

  11. Fontanelles - excessively large

    Science.gov (United States)

    ... Hydrocephalus Intrauterine growth retardation (IUGR) Premature birth Rarer causes: Achondroplasia Apert syndrome Cleidocranial dysostosis Congenital rubella Neonatal hypothyroidism Osteogenesis imperfecta Rickets When to Contact a Medical ...

  12. Stemcell Information: SKIP000815 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available SKIP000815 ... Diseased ACH-8857-1 ACH-8857-1 ... 軟骨無形成症 Q774 Achondroplasia 10080...0 ... 34 30-39 Male Japanese Japanese Yes No Achondroplasia(GM08857)-specific iPSC.GM08857 is from the father of GM08859. 軟骨無形成症

  13. Preserved fertility in a non-mosaic Klinefelter patient with a mutation in the fibroblast growth factor receptor 3 gene

    DEFF Research Database (Denmark)

    Juul, A; Aksglaede, L; Lund, A M

    2007-01-01

    receptor 3 (FGFR3) gene, which is a gain-of-function mutation resulting in achondroplasia. The patient had phenotypic characteristics of achondroplasia (e.g. short limbed dwarfism and frontal bossing). Testicular volume was 8 ml at 27 years of age and repeated semen samples showed sperm concentrations of 0...

  14. Stemcell Information: SKIP000816 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available SKIP000816 ... Diseased ACH-8858-6 ACH-8858-6 ... 軟骨無形成症 Q774 Achondroplasia 10080...0 ... 30 30-39 Female Japanese Japanese Yes No Achondroplasia(GM08858)-specific iPSC.GM08858 is from the mother of GM08859. 軟骨無形成

  15. Impairment of the transition from proliferative stage to prehypertrophic stage in chondrogenic differentiation of human induced pluripotent stem cells harboring the causative mutation of achondroplasia in fibroblast growth factor receptor 3

    Directory of Open Access Journals (Sweden)

    Naohiro Horie

    2017-06-01

    Conclusions: These results suggested that chondrocyte maturation was impaired between the proliferative stage and prehypertrophic stage in the chondrocytes of ACH. The development of chemical compounds which affect the specific maturation stage of chondrocytes is expected to contribute to the ACH treatment, and FGFR3 genome-edited hiPSCs will be a valuable tool in such research studies.

  16. SAJCH 448 NEW.indd

    African Journals Online (AJOL)

    Holistic care for patients involves not only treating their biological or physical ... Achondroplasia is the commonest form of short-limbed dwarfism, affecting 1 in 26 ... The diagnosis is reliably made on clinical and radiological grounds. (Table 1) ...

  17. Combined spinal and epidural anaesthesia for an elective ...

    African Journals Online (AJOL)

    2012-02-02

    Feb 2, 2012 ... This was followed by the injection of. 2 ml normal saline into the ... expressed feeling minimal discomfort during the application of fundal pressure to .... CSE anaesthesia as a safe technique in a parturient with achondroplasia ...

  18. Disease: H00505 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00505 FGFR3-related short limb skeletal dysplasias, including: Achondroplasia [DS...:H01749]; Hypochondroplasia; Thanatophoric dysplasia [DS:H01750]; Severe achondroplasia with developmental d...elay and acanthosis nigricans (SADDAN) FGFR3-related short limb skeletal dysplasias are a group of dwarfisms...tions by disrupting endochondral bone growth. Skeletal dysplasia FGFR3 [HSA:2261] [KO:K05094] ... ICD-10: ...HORS ... Cohen MM Jr ... TITLE ... Some chondrodysplasias with short limbs: molecular

  19. Selfish spermatogonial selection

    DEFF Research Database (Denmark)

    Lim, Jasmine; Maher, Geoffrey J; Turner, Gareth D H

    2012-01-01

    The dominant congenital disorders Apert syndrome, achondroplasia and multiple endocrine neoplasia-caused by specific missense mutations in the FGFR2, FGFR3 and RET proteins respectively-represent classical examples of paternal age-effect mutation, a class that arises at particularly high frequenc......The dominant congenital disorders Apert syndrome, achondroplasia and multiple endocrine neoplasia-caused by specific missense mutations in the FGFR2, FGFR3 and RET proteins respectively-represent classical examples of paternal age-effect mutation, a class that arises at particularly high...

  20. Stemcell Information: SKIP000817 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available SKIP000817 ... Diseased ACHhomo-8859-3 ACHhomo-8859-3 ... 軟骨無形成症 Q774 Achondroplasia... 100800 ... 0-9 Female Japanese Japanese Yes No Achondroplasia(GM08859)-specific iPSC.GM08859 is from... the homozygous child of GM08857 and GM08858. 軟骨無形成症患者(GM08859)繊維芽細胞由来iPS細胞。|GM08859はGM08858の母親とGM08857の父親の子

  1. SEVERE PULMONARY HYPERTENSION DUE TO SLEEP-DISORDERED BREATHING IN AN ACHONDROPLASIC CHILD

    Directory of Open Access Journals (Sweden)

    Vehbi Dogan

    2014-03-01

    Full Text Available Achondroplasia is the most common skeletal dysplasia in children. Achondroplasic patients often have respiratory problems associated with upper respiratory tract obstruction and craniaofacial dysmorphology. Chronic hypoxemia in these patients can result in pulmonary hypertension. In this report an achondroplasic child with severe day-time pulmonary hypertension is presented. [J Contemp Med 2014; 4(1.000: 41-43

  2. Cloverleaf skull with generalised bone dysplasia

    International Nuclear Information System (INIS)

    Kozlowski, K.; Warren, P.S.; Fisher, C.C.; Royal Hospital for Women, Camperdown

    1985-01-01

    A case of cloverleaf skull with generalised bone dysplasia is reported. The authors believe that bone dysplasia associated with cloverleaf is neither identical with thanatophoric dysplasia nor achondroplasia. Until identity of thanatophoric dysplasia and cloverleaf skull with generalised bone dysplasia is proved the diseases should be looked upon as separate entities and the wording ''thanatophoric dysplasia with cloverleaf skull'' should be abolished. (orig.)

  3. FGFR4 Downregulation of Cell Adhesion in Prostate Cancer

    Science.gov (United States)

    2008-09-01

    in Figure 1, all constructs were stably incorporated into 293-RXR cells and were inducible upon treatment with Ponasterone A. Though we had created...through the transmembrane domain, similar to the FGFR3 Gly380Arg mutation responsible for human dwarfism , or achondroplasia. In this model, the FGFR4

  4. Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population

    OpenAIRE

    Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

    2015-01-01

    Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and l...

  5. Consanguinity and its relevance to clinical genetics

    African Journals Online (AJOL)

    Rabah M. Shawky

    2013-01-29

    Jan 29, 2013 ... Autosomal dominant e.g. Marfan's syndrome and achondroplasia. ... In X-linked diseases consanguineous marriage was de- tected in all cases of ..... government should put strict laws for premarital tests. Conflict of interest .... V. Genetic contribution to high neonatally lethal malformation rate in the United ...

  6. Dwarfism and gigantism in historical picture postcards.

    Science.gov (United States)

    Enderle, A

    1998-01-01

    A collection of 893 historical picture postcards from 1900 to 1935, depicting dwarfs and giants, was analysed from medical and psychosocial viewpoints. In conditions such as 'bird headed dwarfism', achondroplasia, cretinism, so-called Aztecs or pinheads, Grebe chondrodysplasia, and acromegalic gigantism, the disorder could be diagnosed easily. In hypopituitary dwarfism, exact diagnosis was more difficult because of heterogeneity. The most common conditions depicted were pituitary dwarfism and achondroplasia. Most of those with gigantism had pituitary gigantism and acromegaly. Brothers and sisters or parents and their children provided evidence of mendelian inheritance of some of these disorders. The cards suggest that being put on show provided, at least in some cases, social benefits. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9764085

  7. Multiple exostotic hypochondroplasia: Syndrome of combined hypochondroplasia and multiple exostoses

    International Nuclear Information System (INIS)

    Dominguez, R.; Young, L.W.; Girdany, B.R.; Steele, M.W.

    1984-01-01

    This is a report of a family with major focus on the daughter who had short stature. The mother had hypochondroplasia and the father had multiple exostoses. The daughter's skeletal roentgenograms show features of both hypochondroplasia and multiple exostoses. The roentgenographic, clinical and genetic aspects of these skeletal dysplasias are reviewed and hypochrondroplasia is contrasted with achondroplasia. The genetic and counseling implications of the association of hypochondroplasia and multiple exostoses are discussed. (orig.)

  8. Den molekylaergenetiske baggrund for en raekke arvelige kraniosynostoser og kondrodysplasier

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; juncker, Inger; Christensen, L

    2001-01-01

    Fibroblast growth factors are structurally related proteins associated with cell growth, differentiation, migration, wound healing, angiogenesis, and oncogenesis. At the cellular level, their function is mediated by transmembrane tyrosinekinase receptors, fibroblast growth factor receptors. Four ......, ACS. The same mutation can cause different syndromes, and the same syndrome can be caused by mutations in different genes. The chondrodysplasias: achondroplasia, hypochondroplasia, and thanatophoric dysplasia are all caused by mutations in FGFR3....

  9. Cloverleaf skull with generalised bone dysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Warren, P.S.; Fisher, C.C.

    1985-09-01

    A case of cloverleaf skull with generalised bone dysplasia is reported. The authors believe that bone dysplasia associated with cloverleaf is neither identical with thanatophoric dysplasia nor achondroplasia. Until identity of thanatophoric dysplasia and cloverleaf skull with generalised bone dysplasia is proved the diseases should be looked upon as separate entities and the wording ''thanatophoric dysplasia with cloverleaf skull'' should be abolished.

  10. Multiple exostotic hypochondroplasia: Syndrome of combined hypochondroplasia and multiple exostoses

    Energy Technology Data Exchange (ETDEWEB)

    Dominguez, R.; Young, L.W.; Girdany, B.R.; Steele, M.W.

    1984-07-01

    This is a report of a family with major focus on the daughter who had short stature. The mother had hypochondroplasia and the father had multiple exostoses. The daughter's skeletal roentgenograms show features of both hypochondroplasia and multiple exostoses. The roentgenographic, clinical and genetic aspects of these skeletal dysplasias are reviewed and hypochrondroplasia is contrasted with achondroplasia. The genetic and counseling implications of the association of hypochondroplasia and multiple exostoses are discussed.

  11. Chromosomal aberrations in children exposed to diagnostic x-rays

    International Nuclear Information System (INIS)

    Nordenson, I.; Beckman, G.; Beckman, L.; Lemperg, R.

    1980-01-01

    Among children who have received high x-ray doses congenital dislocation of the hip joint is the predominating diagnosis. In a series of 9 children who had received high x-ray doses (8 with luxation of the hip joint and one with achondroplasia) a significant increase of chromosomal aberrations was found. The increase concerned mainly chromosome type aberrations. The shorter the time since the last x-ray investigation the higher was the frequency of chromosome type aberrations. (author)

  12. Fibroblast Growth Factor Receptor-4 and Prostate Cancer Progression

    Science.gov (United States)

    2007-10-01

    difference between the two FGFR-4 variants? Achondroplasia ( dwarfism ) is caused by a similar mutation in FGFR-3 (Gly380 to Arg380). Increased FGFR-3...US men, with approximately 230,000 new cases and 29,000 deaths in 2004 [1]. Prostate cancer deaths are a result of metastatic disease and treatment of...such metastatic disease is one of the major therapeutic challenges in prostate cancer treatment . Many studies have been focused on identification of

  13. Dwarfism and gigantism in historical picture postcards.

    OpenAIRE

    Enderle, A

    1998-01-01

    A collection of 893 historical picture postcards from 1900 to 1935, depicting dwarfs and giants, was analysed from medical and psychosocial viewpoints. In conditions such as 'bird headed dwarfism', achondroplasia, cretinism, so-called Aztecs or pinheads, Grebe chondrodysplasia, and acromegalic gigantism, the disorder could be diagnosed easily. In hypopituitary dwarfism, exact diagnosis was more difficult because of heterogeneity. The most common conditions depicted were pituitary dwarfism and...

  14. Ellis Van Creveld Syndrome: Report of a Case and Brief Literature Review

    OpenAIRE

    Gholamhossein Amirhakimi; Hedyeh Saneifard

    2008-01-01

    Objective: Ellis van Creveld syndrome (EvCS) is a rare autosomal recessive (AR) disorder first described in 1940. The syndrome manifests with several skeletal, oral mucosal and dental anomalies, congenital cardiac defects and nail dysplasia. EvCs should be differentiated from other chondrodystrophies such as achondroplasia and Morquios syndrome.Case Presentation: A nine-year old girl was referred with short stature. In physical examination her height was 105 cm. She had normal intelligence, s...

  15. Not all hypochondroplasia families are linked to chromosome 4p16.3

    Energy Technology Data Exchange (ETDEWEB)

    Rousseau, F.; Munnich, A.; Merrer, M.Le. [INSERM, Paris (France)] [and others

    1994-09-01

    Achondroplasia (ACH, MIM 100800) and hypochondroplasia (HCH, MIM 146000) are short limb dwarfism with enlarged head sharing some specific radiological features. Inter- and intrafamilial clinical variability and histolopathological aspects of the growth cartilage suggested that ACH and HCH are allelic disorders. Recently, the gene for achondroplasia was mapped to chromosome 4p and no recombinants were found in 9 families with hypochondroplasia between D4S111 and the telomere (Zmax=1.70, {theta}=0). By using an additional polymorphic DNA marker which detects VNTR-like polymorphism at the D4S227 locus and a new microsatellite at locus D4S? (AFM163yc1), we observed recombinant events with markers of the chromosome 4p16.3 in 3/10 hypochondroplasia families, indicating that not all hypochondroplasia families are linked to chromosome 4p. A fibroblast growth factor receptor (FGFR3) expressed in chondrocytes during endochondral ossification which is located in the 2.5 Mb candidate region for achondroplasia was regarded as a good candidate gene. No major rearrangement of the FGFR3 gene was detected by Southern blot analysis using an FGFR3 cDNA probe. Further investigations will be required to conclude as to the possible involvement of this gene in ACH.

  16. Fracture following lower limb lengthening in children: a series of 58 patients.

    Science.gov (United States)

    Launay, F; Younsi, R; Pithioux, M; Chabrand, P; Bollini, G; Jouve, J-L

    2013-02-01

    Fracture is one of the main complications following external fixator removal used in cases of progressive lower limb lengthening; rates as high as 50% are found in the literature. The aim of this study was to determine the factors influencing this complication. One hundred and eleven cases of lower limb lengthening were performed in 58 patients (40 femurs and 71 tibias). The mean age at surgery was 10.1years old. Lengthening was performed in all cases with an external fixator alone, associated in 39.6% of cases with intramedullary nailing. The patients were divided into three groups according to disease etiology (congenital, achondroplasia and other). The fractures were classified according to the Simpson classification. Twenty fractures were recorded (18%). Sixteen fractures were found in patients with congenital disease, four with achondroplasia and none in the group of other etiologies. The fracture was more often in the femur (27.5%) than in the tibia (12.7%). The rate of fracture is influenced by different factors depending on the etiology of disease. In congenital diseases, the fracture rate is higher when there is lengthening of more than 15% of the initial length and a delay between surgery and the beginning of lengthening of less than 7days. In patients with achondroplasia, the influence of a relative percentage of lengthening is less important than in those with congenital disease. However, to avoid fractures, lengthening should not be started in children under the age of nine. Moreover, lengthening should begin at least 7days after the fixator has been placed. Retrospective. Level IV. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  17. Morquio syndrome: A radiological diagnosis

    Directory of Open Access Journals (Sweden)

    Sadhanandham Shrinuvasan

    2015-01-01

    Full Text Available Mucopolysaccharidoses (MPS are a family of inherited metabolic diseases that results from the deficiency of lysosomal enzymes involved in the degradation of the glycosaminoglycans (MPS. We report here a 7-year-old female child who presented with complaints of short stature, skeletal deformities, and difficulty in walking with normal intelligence. A clinical diagnosis with differential diagnosis of achondroplasia/rickets was considered. Skeletal survey showed radiological features characteristic of Morquio syndrome (MPS IV which lead to diagnosis in this case.

  18. 78. Coronary bypass using bilateral internal mammary arteries in an achondroplast

    Directory of Open Access Journals (Sweden)

    Mohamed Abdulwahab Alassal

    2015-10-01

    Full Text Available Coronary bypass grafting for ischemic heart disease in achondroplastic dwarfs is very rare. Shortage of veins and sometimes, inadequate vein quality can cause difficulties during surgery. Only two achondroplastic cases were reported in literature that underwent coronary bypass surgery, in which the left internal mammary artery and vein grafts were used. To the best of our knowledge using bilateral internal mammary arteries in such patients was not reported. We report here a 55 years old male achondroplastic dwarf who had triple vessels coronary disease that underwent successful coronary bypass surgery using bilateral mammary arteries. Anatomic and surgical challenges in achondroplasia are highlighted

  19. Systemically induced changes in skeletal structure

    International Nuclear Information System (INIS)

    Van Derslice, R.

    1989-01-01

    The number of systemic designs leading the radiographically detectable bone and joint changes is legion. Some disorders (notably the arthridites), while qualifying as diseases with protean systemic manifestations are discussed elsewhere in this book. Other disorders (e.g., achondroplasia), while not representing diseases per se, are included in this chapter for the sake of completeness and due to their relative frequency and their interesting radiographic characteristics. The author focuses on a number of selected conditions, some commonly seen and some relatively infrequently encountered. They are classified into he following categories: endocrinologic; metabolic; hematologic and reticuloendothelial; and dysplastic

  20. Llizarov technique

    International Nuclear Information System (INIS)

    Shankman, S.; Rosenberg, Z.S.; Frankel, V.; Golyakhovsky, V.

    1990-01-01

    This paper illustrates the radiographic manifestations of the Ilizarov distraction technique for the correction of short and deformed limbs. The radiographs of 130 patients who underwent Ilizarov distraction at 160 sites since December 1986 were reviewed retrospectively. Reasons for correction included fracture nonunion and malunion idiopathic leg length discrepancy, achondroplasia, and neurofibromatosis with tibial pseudarthrosis. Ninety patients were adults, and 40 were children. In order to assess cortical bone development during the fixation phase, CT of the regenerate bone was performed in 17 patients. Conventional tomograms were obtained in 20 patients for the evaluation of delayed or hypoplastic union at the distraction site

  1. Tópicos sobre displasias óseas

    Directory of Open Access Journals (Sweden)

    Guillermo Lay-Son R.

    2012-02-01

    Full Text Available It is important to recognize skeletal dysplasia as a heterogeneous group of conditions with many classifications all of which have shortcomings. In consequence, it is very important to obtain anthropometric measurements and a complete skeletal work-up so as to properly establish phenotype. Once this is done patients can be assigned to diagnostic groups and diagnosis may be established. Diagnosing conditions that do not belong to the more common and well known diseases – such as achondroplasia – is more challenging and requires a multi-disciplinary approach.

  2. Sleep Disorders in Childhood Neurogenetic Disorders

    Directory of Open Access Journals (Sweden)

    Laura Beth Mann Dosier

    2017-09-01

    Full Text Available Genetic advances in the past three decades have transformed our understanding and treatment of many human diseases including neurogenetic disorders. Most neurogenetic disorders can be classified as “rare disease,” but collectively neurogenetic disorders are not rare and are commonly encountered in general pediatric practice. The authors decided to select eight relatively well-known neurogenetic disorders including Down syndrome, Angelman syndrome, Prader–Willi syndrome, Smith–Magenis syndrome, congenital central hypoventilation syndrome, achondroplasia, mucopolysaccharidoses, and Duchenne muscular dystrophy. Each disorder is presented in the following format: overview, clinical characteristics, developmental aspects, associated sleep disorders, management and research/future directions.

  3. Ovarian Spigelian hernia: A radiological diagnosis

    International Nuclear Information System (INIS)

    Hill, Ciaran Scott; Chahil, Balvinder; Marlow, Benjamin

    2012-01-01

    We describe that case of a 54 year old lady with achondroplasia who presented with ongoing left sided abdominal pain. Ultrasound and abdominal computerized tomography images demonstrated an enlarged left ovary and Fallopian tube trapped between the rectus abdominus and the lateral semilunar line under cover of the external oblique aponeurosis. A left sided salpingoophrectomy with mesh herniorrhaphy was performed and histological analysis confirmed the hernia contents were a hydrosalpinx and normal ovary. This case report presents the unusual radiographic images and intraoperative photographs of an ovarian Speglian hernia.

  4. Fixed cord in spinal stenosis

    International Nuclear Information System (INIS)

    Levy, L.M.; Wang, H.; Francomano, C.; Hurko, O.; Carson, B.; Heffez, D.S.; DiChiro, G.; Bryan, R.N.

    1990-01-01

    This paper evaluates patients with cervical spinal canal compromise due to congenital anomalies (achondroplasia, Chiari malformation) and degenerative diseases using MR cord motion and cerebrospinal fluid (CSF) flow studies. Pulsatile longitudinal motion of the cervical cord was determined by means of cardiac-gated velocity phase contrast methods, including cine. Pathology included dwarfism (n = 15), Chiari malformation (n = 10), spondylosis (n = 10), and acute cord compression (n = 9). Symptomatic cases of congenital cervical stenosis had decreased cord motion, although CSF flow was not always significantly compromised. Postoperative cases demonstrated good cord and CSF motion, unless compression or obstruction was present

  5. Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador.

    Science.gov (United States)

    Bernal, J E; Briceno, I

    2006-09-01

    The people of Tumaco-La Tolita culture inhabited the borders of present-day Colombia and Ecuador. Already extinct by the time of the Spaniards arrival, they left a huge collection of pottery artifacts depicting everyday life; among these, disease representations were frequently crafted. In this article, we present the results of the personal examination of the largest collections of Tumaco-La Tolita pottery in Colombia and Ecuador; cases of Down syndrome, achondroplasia, mucopolysaccharidosis I H, mucopolysaccharidosis IV, a tumor of the face and a benign tumor in an old woman were found. We believe these to be among the earliest artistic representations of disease.

  6. Severe spinal stenosis in an adult achondroplastic dwarf – case report

    Directory of Open Access Journals (Sweden)

    B. Iliescu1, S. Gaivas1, C. Apetrei1, I. Poeată1,2

    2010-11-01

    Full Text Available Achondroplasia is the most commonform of human short-limbed dwarfism andis one of a spectrum of diseases caused bymutations in the FGFR3 gene.Achondroplasia is estimated to occur in 1 in10,000–30,000 live births4,7. The disease isautosomal dominant, but 80% of patientshave new mutations. It is commonlyassociated with several neurologicalconditions such as hydrocephalus,cervicomedullary compression, cervical orthoracic cord compression, and lumbarspinal compression due to bone stenosisalong the neuraxis. We report a case withsevere spinal stenosis at the lumbar andthoracic levels, with minimal involvementof the cervical spine with late neurologicalonset in an adult patient withachondroplasia. Neurological andradiological findings and surgicalprocedures are discussed. The patient wasadmitted with profound spastic lowerparaparesis and urinary incontinence. In thefirst operation we performed lumbardecompression and the patient improvedand on the fifth day she was able to take ashort walk. 3 months after the first surgerywe intervened on the thoracic spine with amulti-level decompression which allowedfor further neurological improvement,continued in a specialized medical facility.The case stands out as the clinical picturewas dominated by the lumbar stenosis(although both lumbar and thoracicstenosis were severe at the time ofpresentation with a late onset and sparingof the cervical spine.

  7. Total spinal anesthesia in an achondroplasic patient: case report

    Directory of Open Access Journals (Sweden)

    Amiri H R

    2008-06-01

    Full Text Available Background: Total spinal anesthesia is a complication of lumbar epidural anesthesia following undiagnosed subarachnoid or subdural injection of local anesthetic. Although many achondroplastic dwarfs have a normal spine, catheter insertion may be more problematic with a narrow epidural space making a subarachnoid tap more probable.  Other malformations associated with achondroplasia, such as prolapsed intervertebral discs, reduced interpedicular distance, shortened pedicles, and osteophyte formation, combined with a narrow epidural space may make identification of the space difficult and increases the risk of dural puncture. Furthermore, subarachnoid tap or dural puncture may be hard to recognize if a free flow of CSF is difficult to achieve due spinal stenosis. Yet, for those who meet the criteria, epidural regional anesthesia is frequently preferred over other forms, which often have more or more dangerous side effects in this type of patient.Case report: A 22-year-old achondroplastic male dwarf patient was scheduled for pelvic mass resection and was considered a candidate for continuous epidural anesthesia. The anesthesia became complicated by total spinal anesthesia, which was reversed following supportive management for about two hours.Conclusion: There is significant debate over the composition and volume of the test dose, especially for patients with achondroplasia. We nevertheless recommend repeated test-doses during the accomplishment of epidural anesthesia to exclude unintended intravascular, intrathecal or subdural injection, keeping in mind that a test dose of local anesthetic does not completely prevent complications.

  8. Hypochondroplasia with Foramen Magnum Stenosis: a Case Report

    Directory of Open Access Journals (Sweden)

    Nazik Aşılıoğlu

    2011-09-01

    Full Text Available Hypochondroplasia was first reported in the English literature by Beals (1969. The features are similar to those of achondroplasia but are less severe and are usually reported not to involve the skull. The foramen magnum and whole spinal canal are reduced in diameter in achondroplasia, but less so in hypochondroplasia. In this study, we present an unique case of a seven month old child with hypochondroplasia with symptomatic foramen magnum stenosis which required surgical decompression. This 7-month-old child with hypochondroplasia presented with hypotonia and severe respiratory disabilities, including apneic episodes requiring continuous positive airway pressure. Magnetic resonance imaging revealed marked foramen magnum stenosis. Foramen magnum decompression was performed. Postoperatively, steady motor improvement has been observed and the patient no longer requires ventilatory support. To the our knowledge, this is the first report of hypochondroplasia and symptomatic foramen magnum stenosis. In this case we wish to emphasize the necessity of the radiological imaging of foramen magnum and spinal cord for the patient who has respiratory distress and hypotonia with skeletal dysplasia.

  9. Interpretation and value of MR CSF flow studies for paediatric neurosurgery

    Directory of Open Access Journals (Sweden)

    Samukelisiwe Sithembile Mbonane

    2013-03-01

    Full Text Available Imaging techniques may be underutilised when clinicians are unaware of the technique or do not recognise its potential. Phase-contrast MR imaging (PC-MRI is a rapid, simple and non-invasive technique that is sensitive to CSF flow. It demonstrates a mechanical coupling between cerebral blood and CSF flow throughout the cardiac cycle. Neurosurgeons should be able to request this procedure routinely as part of an MRI request. This paper gives an overview of the indications, technical requirements, technique and interpretation, using image examples. Indications for CSF flow studies include assessment and functionality of shunt treatment in patients with hydrocephalus; hydrocephalus associated with achondroplasia; Chiari I malformation; confirmation of aqueductal stenosis; and determining patency of a third ventriculostomy.

  10. Atlantoaxial Subluxation due to an Os Odontoideum in an Achondroplastic Adult: Report of a Case and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Abolfazl Rahimizadeh

    2015-01-01

    Full Text Available The authors report the first example of an adult achondroplastic dwarf with progressive quadriparesis secondary to atlantoaxial subluxation as a consequence of an os odontoideum. Actually, craniocervical region is a frequent site of compression and myelopathy in achondroplasia particularly in children as a result of small foramen magnum and hypertrophied opisthion. Moreover, very rarely in achondroplastic patients, coexistence of atlantoaxial instability as the sequel of os odontoideum can result in further compression of the already compromised cervicomedullary neural tissues, the scenario that has been reported only in five achondroplastic children. Herein, a 39-year-old achondroplastic male suffering such an extremely rare combination is presented. With C1-C2 screw rod instrumentation, atlas arch laminectomy, limited suboccipital craniectomy, and release of dural fibrous bands, reduction, decompression, and stabilization could be achieved properly resulting in steady but progressive recovery.

  11. Anaesthetic Management of Caesarean Section in an Achondroplastic Dwarf

    Directory of Open Access Journals (Sweden)

    Kirti N Saxena

    2008-01-01

    A twenty year old parturient with short stature presented to the hospital in early labour. An elective lower segment caesarean section(LSCS was planned in view of cephalopelvic disproportion. She had papers which suggested that she had been diagnosed as a case of achondroplasia though details were not available. Combined spinal epidural(CSE anaesthesia was planned in the patient in view of the death of her first baby following caesarean section under general anaesthesia. Repeatedly dry taps were achieved on attempting dural puncture. Dural puncture was abandoned and an 18 G epidural catheter was threaded via the Tuohy needle. Sensory block till T 6 was achieved with 6ml of local anaesthetic solution. The patient was stable during the intraoperative and postoperative period.

  12. Perceval S aortic valve implantation in an achondroplastic Dwarf

    Directory of Open Access Journals (Sweden)

    Nikolaos G Baikoussis

    2016-01-01

    Full Text Available Despite cardiovascular disease in patients with dwarfism is not rare; there is a lack of reports referring to cardiac interventions in such patients. Dwarfism may be due to achondroplasia or hormonal growth disorders. We present a 58-year-old woman with episodes of dyspnea for several months. She underwent on transthoracic echocardiography, and she diagnosed with severe aortic valve stenosis. She referred to our department for surgical treatment of this finding. In accordance of her anthropometric characteristics and her very small aortic annulus, we had the dilemma of prosthesis selection. We decided to implant a stentless valve to optimize her effective orifice area. Our aim is to present the successful Perceval S valve implantation and the descriptions of the problems coming across in operating on these special patients. To our knowledge, this is the first case patient in which a Perceval S valve is implanted according to the international bibliography.

  13. Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean Population.

    Directory of Open Access Journals (Sweden)

    Eun Jin Woo

    Full Text Available Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias.

  14. Failed rapid sequence induction in an achondroplastic dwarf

    Directory of Open Access Journals (Sweden)

    Jasleen Kaur

    2011-01-01

    Full Text Available Achondroplasia, a common cause of short limbed type of dwarfism is due to quantitative decrease in rate of endochondral ossification. This abnormal bone growth leads to disproportionate body and head structure, thus placing them under high risk for anaesthetic management. There is paucity in literatures, regarding appropriate drug dosage selection in these patients. Use of drugs as per standard dosage recommendations based on body weight or body surface area, may not be adequate in these patients owing to discrepancies in overall body weight and lean body weight, especially during rapid sequence induction. Here, we report a case of failed rapid sequence induction due to abnormal response to administered drugs in an adult achondroplastic dwarf. Standard doses of thiopentone and rocuronium had to be repeated thrice to achieve adequate conditions for intubation.

  15. Chondroectodermal dysplasia (Ellis van Creveld syndrome: A report of three cases with review of literature

    Directory of Open Access Journals (Sweden)

    Kurian K

    2007-01-01

    Full Text Available Chondroectodermal dysplasia is a rare mesenchymal - ectodermal dysplasia first described in 1940 by Richard W.B. Ellis and Simon van Creveld now known as Ellis van Creveld syndrome. It is also known as Mesvectodermal dysplasia. Majority of cases were characteristically seen in one particular inbred population from the Amish community of Lancaster County, Pennsylvania, U.S.A. The syndrome manifests with several skeletal anomalies, oral mucosal and dental anomalies, congenital cardiac defects and nail dysplasia. Ellis van Creveld syndrome may be differentiated from other chondrodystrophies like achondroplasia, chondroplasia punctata, asphyxiating thorasic dystrophy and Morquio′s syndrome. The presence of oral mucosal and dental alterations like notching of the lower alveolar process, fusion of the upper lip with gingival mucosal margin, occasional presence of neonatal teeth, oligodontia and conical shape of anterior teeth will confirm the diagnosis of Ellis van Creveld syndrome and hence its importance to dentists.

  16. Small is challenging; distal femur fracture management in an elderly lady with achondroplastic dwarfism.

    Science.gov (United States)

    Murphy, Colin G; Chrea, Bopha; Molloy, Alan P; Nicholson, Paul

    2013-03-20

    Achondroplasia is an autosomal dominant dwarfing condition that represents the most common form of skeletal dysplasia. The disease is caused by a mutation in the gene encoding fibroblast growth factor receptor 3 (FGFR3) found at the p16.3 locus on chromosome 4 which results in severe inhibition of subchondral bone growth. Anatomic variations, including articular and periarticular deformities classically seen with this condition, amplify the complexity of fracture fixation. Blood volume loss, age-related bone fragility, component selection and positioning pose serious orthopaedic challenges. Concomitant cardiovascular, respiratory and neurological comorbidities pose additional high-risk perioperative considerations. Despite an estimated prevalence of 1:25 000 in the general population, there is little literature concerning the operative and postoperative treatment challenges faced by orthopaedic surgeons dealing with fracture management on a patient with this condition. We present a case of an intercondylar femoral fracture in an elderly achondroplastic lady successfully treated with percutaneous screw fixation.

  17. The gene for the Ellis-van Creveld syndrome is located on chromosome 4p16

    Energy Technology Data Exchange (ETDEWEB)

    Polymeropoulos, M.H.; Ide, S.E. [National Institute of Health, Bethesda, MD (United States); Wright, M. [Univ. of Newcastle Upon Tyne (United Kingdom)] [and others

    1996-07-01

    Ellis-van Creveld syndrome (EVC) is an autosomal recessive disorder characterized by disproportionate dwarfism, polydactyly, and congenital heart disease. This rare disorder is found with increased frequency among the Old Order Amish community in Lancaster County, Pennsylvania. We have used linkage analysis to localize the gene responsible for the EVC phenotype in nine interrelated Amish pedigrees and three unrelated families from Mexico, Ecuador, and Brazil. We now report the linkage for the Ellisvan Creveld syndrome gene to markers on the distal short arm of human chromosome 4, with Z{sub max} = 6.91 at {theta} = 0.02 for marker HOX7, in a region proximal to the FGFR3 gene responsible for the achondroplasia phenotype. 17 refs., 2 figs., 1 tab.

  18. The Utrecht approach to exercise in chronic childhood conditions: the decade in review.

    Science.gov (United States)

    van Brussel, Marco; van der Net, Janjaap; Hulzebos, Erik; Helders, Paul J M; Takken, Tim

    2011-01-01

    To summarize and discuss current evidence and understanding of clinical pediatric exercise physiology focusing on the work the research group at Utrecht and others have performed in the last decade in a variety of chronic childhood conditions as a continuation of the legacy of Dr Bar-Or. The report discusses current research findings on the cardiopulmonary exercise performance of children (and adolescents) with juvenile idiopathic arthritis, osteogenesis imperfecta, achondroplasia, hemophilia, cerebral palsy, spina bifida, cystic fibrosis, and childhood cancer. Exercise recommendations and contraindications are provided for each condition. Implications for clinical practice and future research in this area are discussed for each of the chronic conditions presented. The authors provide a basic framework for developing an individual and/or disease-specific training program, introduce the physical activity pyramid, and recommend a core set of clinical measures to be used in clinical research.

  19. Perceval S aortic valve implantation in an achondroplastic Dwarf.

    Science.gov (United States)

    Baikoussis, Nikolaos G; Argiriou, Michalis; Argiriou, Orestis; Dedeilias, Panagiotis

    2016-01-01

    Despite cardiovascular disease in patients with dwarfism is not rare; there is a lack of reports referring to cardiac interventions in such patients. Dwarfism may be due to achondroplasia or hormonal growth disorders. We present a 58-year-old woman with episodes of dyspnea for several months. She underwent on transthoracic echocardiography, and she diagnosed with severe aortic valve stenosis. She referred to our department for surgical treatment of this finding. In accordance of her anthropometric characteristics and her very small aortic annulus, we had the dilemma of prosthesis selection. We decided to implant a stentless valve to optimize her effective orifice area. Our aim is to present the successful Perceval S valve implantation and the descriptions of the problems coming across in operating on these special patients. To our knowledge, this is the first case patient in which a Perceval S valve is implanted according to the international bibliography.

  20. Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population.

    Science.gov (United States)

    Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

    2015-01-01

    Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias.

  1. Future directions in research

    International Nuclear Information System (INIS)

    Hall, J.G.; Lopez-Rangel, E.

    1996-01-01

    New studies of the effects of ionizing radiation on the human genome must include not only its effect on the sequence of a particular gene, but must also consider the possible location, complete structure, regulation, and function of the gene as well. Historically, genetic disorders have been characterized as single gene disorders, chromosomal aberrations, and multifactorial disorders. Now, however, the following have to be considered: mosaicism, genomic imprinting, uniparental disomy, cytoplasmic inheritance, allelic expansion. Molecular techniques that may be useful in analyzing radiation damage include Fluorescent In Situ Hybridization and the Polymerase Chain Reaction. The effect of radiation on the fibroblast growth factor receptor 3, damage to which is associated with the development of achondroplasia, is recommended as a fruitful, if complicated, research topic

  2. Lumbar gibbus in storage diseases and bone dysplasias

    Energy Technology Data Exchange (ETDEWEB)

    Levin, T.L. [Department of Radiology, Division of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States); Berdon, W.E. [Department of Radiology, Division of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States); Lachman, R.S. [International Skeletal Dysplasia Registry, Los Angeles, CA (United States); Anyane-Yeboa, K. [Department of Pediatrics, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States); Ruzal-Shapiro, C. [Department of Radiology, Division of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States); Roye, D.P. Jr. [Department of Orthopedic Surgery, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States)

    1997-04-01

    Objective. The objective of this study was to review the problem of lumbar gibbus in children with storage diseases and bone dysplasias utilizing plain films and MR imaging. Materials and methods. Clinical histories and radiographic images in five patients with storage diseases [four mucopolysaccharidosis (MPS) and one mucolipidosis] and two with achondroplasia were reviewed. The International Skeletal Dysplasia Registry (Los Angeles, Calif.), surveyed for all patients with lumbar gibbus and skeletal dysplasias, provided 12 additional cases. Results. All patients had localized gibbus of the upper lumbar spine, characterized by anterior wedging and posterior displacement of the vertebrae at the apex of the curve, producing a beaked appearance. The curve, exaggerated in the sitting or standing position, was most severe in the two patients with MPS-IV (one of whom died). Both developed severe neurologic signs and symptoms requiring surgical intervention. In four patients, MR images demonstrated the apex of the curve to be at or below the conus. Two patients demonstrated anterior herniation of the intervertebral discs at the apex of the curve, though the signal intensity of the intervertebral discs was normal. Conclusion. Lumbar gibbus has important neurologic and orthopedic implications, and is most severe in patients with MPS. The etiology of the gibbus with vertebral beaking is multifactorial and includes poor truncal muscle tone, weight-bearing forces, growth disturbance and anterior disc herniation. The curve is generally at or below the conus. Neurologic complications are unusual, although orthopedic problems can arise. Due to their longer survival, patients with achondroplasia or Morquio`s disease are more vulnerable to eventual gibbus-related musculoskeletal complications. (orig.). With 6 figs., 2 tabs.

  3. Lumbar gibbus in storage diseases and bone dysplasias

    International Nuclear Information System (INIS)

    Levin, T.L.; Berdon, W.E.; Lachman, R.S.; Anyane-Yeboa, K.; Ruzal-Shapiro, C.; Roye, D.P. Jr.

    1997-01-01

    Objective. The objective of this study was to review the problem of lumbar gibbus in children with storage diseases and bone dysplasias utilizing plain films and MR imaging. Materials and methods. Clinical histories and radiographic images in five patients with storage diseases [four mucopolysaccharidosis (MPS) and one mucolipidosis[ and two with achondroplasia were reviewed. The International Skeletal Dysplasia Registry (Los Angeles, Calif.), surveyed for all patients with lumbar gibbus and skeletal dysplasias, provided 12 additional cases. Results. All patients had localized gibbus of the upper lumbar spine, characterized by anterior wedging and posterior displacement of the vertebrae at the apex of the curve, producing a beaked appearance. The curve, exaggerated in the sitting or standing position, was most severe in the two patients with MPS-IV (one of whom died). Both developed severe neurologic signs and symptoms requiring surgical intervention. In four patients, MR images demonstrated the apex of the curve to be at or below the conus. Two patients demonstrated anterior herniation of the intervertebral discs at the apex of the curve, though the signal intensity of the intervertebral discs was normal. Conclusion. Lumbar gibbus has important neurologic and orthopedic implications, and is most severe in patients with MPS. The etiology of the gibbus with vertebral beaking is multifactorial and includes poor truncal muscle tone, weight-bearing forces, growth disturbance and anterior disc herniation. The curve is generally at or below the conus. Neurologic complications are unusual, although orthopedic problems can arise. Due to their longer survival, patients with achondroplasia or Morquio's disease are more vulnerable to eventual gibbus-related musculoskeletal complications. (orig.). With 6 figs., 2 tabs

  4. All Madelung deformities are not endocrine.

    Science.gov (United States)

    Kumar, Ajay; Rai, Gopal K; Akhtar, Javed; Phillip, Rajeev; Gutch, Manish; Arya, T V S

    2013-10-01

    Madelung deformity is a rare inherited disorder associated with endocrine disorders like Turner's syndrome, pseudohypoparathyroidism, but can be seen with short stature homeobox deficiency conditions such as Leri-Weill dyschondrosteosis (LWD) and Langers mesomelic dysplasia. It has also been reported following trauma to the distal radius epiphysis neoplasia mucopolysaccharidosis (MPS) and achondroplasia. Madelung deformity is an abnormality of distal radial epiphysis where in progressive ulnar and volar tilt of the articular surface occurring in association with distal subluxation of ulna. A 13-year-old girl was referred to us for evaluation of bilateral deformity of wrist and short stature. There was ulnar deviation and dorsal tilt of bilateral hands without history of pain to the joint trauma and family history of similar illness. On X-ray, wrist showed malformed distal radial epiphysis with dorsal and ulnar shift and with increased length of phalanges suggestive of Madelung deformity. X-ray spine was normal. Ultrasound abdomen showed normal uterus and ovary and her follicle stimulating hormone. Luteinizing hormone was normal and so was urine MPS screening. Based on the above points the diagnosis of LWD was made.

  5. The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation.

    Science.gov (United States)

    Deng, Ang; Zhang, Hongqi; Hu, Minyu; Liu, Shaohua; Wang, Yuxiang; Gao, Qile; Guo, Chaofeng

    2018-01-01

    The proliferative rate of chondrocytes affects bone elongation. Chondrocyte hypertrophy is required for endochondral bone formation as chondrocytes secrete factors required for osteoblast differentiation and maturation. Previous studies have demonstrated that the Indian hedgehog (Ihh) signaling pathway is a key regulator of skeletal development and homeostasis. The aim of the present study was to investigate the function of Ihh in chondrocyte proliferation and differentiation, as well as the underlying mechanisms. Ihh was knocked down in mouse chondrocyte cells using short hairpin RNA. Chondrocyte apoptosis and cell cycle arrest were assessed using flow cytometry and the results indicated that knockdown of Ihh significantly inhibited cell growth (PIhh also resulted in cell cycle arrest at G1 to S phase in chondrocytes. It was also observed that knockdown of Ihh decreased alkaline phosphatase activity and mineral deposition of chondrocytes. The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation may be associated with the transforming growth factor-β/mothers against decapentaplegic and osteoprotegerin/receptor activator of nuclear factor κB ligand signaling pathway. The results of the present study suggest that chondrocyte-derived Ihh is essential for maintaining bone growth plates and that manipulation of Ihh expression or its signaling components may be a novel therapeutic technique for the treatment of skeletal diseases, including achondroplasia.

  6. The acrophysis: a unifying concept for understanding enchondral bone growth and its disorders. II. Abnormal growth

    International Nuclear Information System (INIS)

    Oestreich, Alan E.

    2004-01-01

    In order to discuss and illustrate the effects common to normal and abnormal enchondral bone at the physes and at all other growth plates of the developing child, the term ''acrophysis'' was proposed. Acrophyses include the growth plates of secondary growth centers including carpals and tarsals and apophyses, and the growth plates at the nonphyseal ends of small tubular bones. Abnormalities at acrophyseal sites are analogous to those at the physeal growth plates and their metaphyses. For example, changes relating to the zone of provisional calcification (ZPC) are often important to the demonstration of such similarities. Lead lines were an early example of the concept of analogy from abnormality due to physeal and to acrophyseal disturbance. The ZPC is a key factor in understanding patterns of rickets and its healing. Examples (including hypothyroidism, scurvy and other osteoporosis, Ollier disease, achondroplasia, and osteopetrosis, as well as the family of frostbite, Kashin-Beck disease, and rat bite fever) illustrate the acrophysis principle and in turn their manifestations are explained by that principle. (orig.)

  7. Atlantoaxial subluxation. Radiography and magnetic resonance imaging correlated to myelopathy

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Y.; Takahashi, M.; Sakamoto, Y.; Kojima, R.

    Twenty-nine patients with atlantoaxial subluxation (18 with rheumatoid arthritis, 2 due to trauma, 4 with os odontoideum, and one each with polyarteritis nodosa, rheumatic fever, Klippel-Feil syndrome, achondroplasia, and cause unknown) were evaluated using a 0.22 tesla resistive MRI unit. Cord compression was classified into four grades according to the degree on magnetic resonance imaging. There were 7 patients with no thecal sac compression (grade 0), 10 with a minimal degree of subarachnoid space compression without cord compression (grade 1), 7 with mild cord compression (grade 2), and 5 with severe cord compression or cord atrophy (grade 3). Although the severity of myelopathy showed poor correlation with the atlantodental interval on conventional radiography, high correlation was observed between MR grading and the degree of myelopathy. The high signal intensity foci were observed in 7 or 12 patients with cord compression (grades 2 and 3) on T2 weighted images. Other frequently observed findings in rheumatoid arthritis included soft tissue masses of low to intermediate signal intensity in the paraodontoid space, erosions of the odontoid processes, and atlanto-axial impaction on T1 and T2 weighted images.

  8. Combined spinal epidural anesthesia in achondroplastic dwarf for femur surgery

    Directory of Open Access Journals (Sweden)

    Rochana Girish Bakhshi

    2011-11-01

    Full Text Available Achondroplasia is the commonest form of short-limbed dwarfism and occurs in 1:26,000- 40,000 live births. This is an autosomal dominant disorder with abnormal endochondral ossification whereas periosteal and intramembranous ossification are normal. The basic abnormality is a disturbance of cartilage formation mainly at the epiphyseal growth plates and at the base of the skull. The anesthetic management of achondroplastic dwarfs is a challenge to the anesthesiologist. Both regional as well as general anesthesia have their individual risks and consequences. We report a case of an achondroplastic dwarf in whom combined spinal epidural anesthesia was used for fixation of a fractured femur. The patient had undergone previous femur surgery under general anesthesia since he had been informed that spinal anesthesia could be very problematic. There was no technical difficulty encountered during the procedure and an adequate level was achieved with low-dose local anesthetics without any problem. Postoperative pain relief was offered for three consecutive postoperative days using epidural tramadol. We discuss the anesthetic issues and highlight the role of combined spinal epidural anesthesia with low-dose local anesthetics in this patient. This approach also helped in early ambulation and postoperative pain relief.

  9. Atlantoaxial subluxation

    International Nuclear Information System (INIS)

    Yamashita, Y.; Takahashi, M.; Sakamoto, Y.; Kojima, R.

    1989-01-01

    Twenty-nine patients with atlantoaxial subluxation (18 with rheumatoid arthritis, 2 due to trauma, 4 with os odontoideum, and one each with polyarteritis nodosa, rheumatic fever, Klippel-Feil syndrome, achondroplasia, and cause unknown) were evaluated using a 0.22 tesla resistive MRI unit. Cord compression was classified into four grades according to the degree on magnetic resonance imaging. There were 7 patients with no thecal sac compression (grade 0), 10 with a minimal degree of subarachnoid space compression without cord compression (grade 1), 7 with mild cord compression (grade 2), and 5 with severe cord compression or cord atrophy (grade 3). Although the severity of myelopathy showed poor correlation with the atlantodental interval on conventional radiography, high correlation was observed between MR grading and the degree of myelopathy. The high signal intensity foci were observed in 7 or 12 patients with cord compression (grades 2 and 3) on T2 weighted images. Other frequently observed findings in rheumatoid arthritis included soft tissue masses of low to intermediate signal intensity in the paraodontoid space, erosions of the odontoid processes, and atlanto-axial impaction on T1 and T2 weighted images. (orig.)

  10. Pneumomediastinum, Subcutaneous Emphysema, and Tracheal Tear in the Early Postoperative Period of Spinal Surgery in a Paraplegic Achondroplastic Dwarf

    Directory of Open Access Journals (Sweden)

    Sinan Kahraman

    2013-01-01

    Full Text Available Achondroplasia was first described in 1878 and is the most common form of human skeletal dysplasia. Spinal manifestations include thoracolumbar kyphosis, foramen magnum, and spinal stenosis. Progressive kyphosis can result in spinal cord compression and paraplegia due to the reduced size of spinal canal. The deficits are typically progressive, presenting as an insidious onset of paresthesia, followed by the inability to walk and then by urinary incontinence. Paraplegia can be the result of direct pressure on the cord by bone or the injury to the anterior spinal vessels by a protruding bone. Surgical treatment consists of posterior instrumentation, fusion with total wide laminectomy at stenosis levels, and anterior interbody support. Pedicle screws are preferred for spinal instrumentation because wires and hooks may induce spinal cord injury due to the narrow spinal canal. Pedicle lengths are significantly shorter, and 20–25 mm long screws are appropriate for lower thoracic and lumbar pedicles in adult achondroplastic There is no information about the appropriate length of screws for the upper thoracic pedicles. Tracheal injury due to inappropriate pedicle screw length is a rare complication. We report an extremely rare case of tracheal tear due to posterior instrumentation and its management in the early postoperative period.

  11. The acrophysis: a unifying concept for understanding enchondral bone growth and its disorders. II. Abnormal growth

    Energy Technology Data Exchange (ETDEWEB)

    Oestreich, Alan E. [Department of Radiology, Cincinnati Children' s Hospital Medical Center, 3333 Burnet Avenue, OH 45229-3039, Cincinnati (United States)

    2004-03-01

    In order to discuss and illustrate the effects common to normal and abnormal enchondral bone at the physes and at all other growth plates of the developing child, the term ''acrophysis'' was proposed. Acrophyses include the growth plates of secondary growth centers including carpals and tarsals and apophyses, and the growth plates at the nonphyseal ends of small tubular bones. Abnormalities at acrophyseal sites are analogous to those at the physeal growth plates and their metaphyses. For example, changes relating to the zone of provisional calcification (ZPC) are often important to the demonstration of such similarities. Lead lines were an early example of the concept of analogy from abnormality due to physeal and to acrophyseal disturbance. The ZPC is a key factor in understanding patterns of rickets and its healing. Examples (including hypothyroidism, scurvy and other osteoporosis, Ollier disease, achondroplasia, and osteopetrosis, as well as the family of frostbite, Kashin-Beck disease, and rat bite fever) illustrate the acrophysis principle and in turn their manifestations are explained by that principle. (orig.)

  12. The time of onset of abnormal calcification in spondylometaepiphyseal dysplasia, short limb-abnormal calcification type

    Energy Technology Data Exchange (ETDEWEB)

    Tueysuez, Beyhan [Istanbul University, Department of Pediatric Genetics, Cerrahpasa Medical School, Istanbul (Turkey); Gazioglu, Nurperi [Istanbul University, Department of Neurosurgery, Cerrahpasa Medical School, Istanbul (Turkey); Uenguer, Savas [Istanbul University, Department of Pediatric Radiology, Cerrahpasa Medical School, Istanbul (Turkey); Aji, Dolly Yafet [Istanbul University, Department of Pediatrics, Cerrahpasa Medical School, Istanbul (Turkey); Tuerkmen, Seval [Istanbul University, Department of Pediatric Genetics, Cerrahpasa Medical School, Istanbul (Turkey); Universitatsklinikum Berlin, Charite Virchow-Klinik, Berlin (Germany)

    2009-01-15

    A 1-month-old boy with shortness of extremities on prenatal US was referred to our department with a provisional diagnosis of achondroplasia. His height was normal but he had short extremities and platyspondyly, premature carpal epiphyses on both hands, and short tubular bones with irregular metaphyses on radiographs. Re-evaluation of the patient at the age of 1 year revealed very short height and premature calcification of the costal cartilages and epiphyses. Spondylometaepiphyseal dysplasia (SMED), short limb-abnormal calcification type was diagnosed. This condition is a very rare autosomal recessively inherited disorder, and most of the patients die in early childhood due to neurological involvement. At the age of 2 years and 5 months, a CT scan showed narrowing of the cervical spinal canal. One month later he died suddenly because of spinal cord injury. In conclusion early diagnosis is very important because the recurrence risk is high and patients may die due to early neurological complications. The time of onset of abnormal calcifications, a diagnostic finding of the disease, is at the age of around 1 year in most patients. When abnormal calcifications are not yet present, but radiological changes associated with SMED are present, this rare disease must be considered. (orig.)

  13. Frequency of the allelic variant c.1150T > C in exon 10 of the fibroblast growth factor receptor 3 (FGFR3 gene is not increased in patients with pathogenic mutations and related chondrodysplasia phenotypes

    Directory of Open Access Journals (Sweden)

    Thatiane Yoshie Kanazawa

    2014-12-01

    Full Text Available Mutations in the FGFR3 gene cause the phenotypic spectrum of FGFR3 chondrodysplasias ranging from lethal forms to the milder phenotype seen in hypochondroplasia (Hch. The p.N540K mutation in the FGFR3 gene occurs in ~70% of individuals with Hch, and nearly 30% of individuals with the Hch phenotype have no mutations in the FGFR3, which suggests genetic heterogeneity. The identification of a severe case of Hch associated with the typical mutation c.1620C > A and the occurrence of a c.1150T > C change that resulted in a p.F384L in exon 10, together with the suspicion that this second change could be a modulator of the phenotype, prompted us to investigate this hypothesis in a cohort of patients. An analysis of 48 patients with FGFR3 chondrodysplasia phenotypes and 330 healthy (control individuals revealed no significant difference in the frequency of the C allele at the c.1150 position (p = 0.34. One patient carrying the combination `pathogenic mutation plus the allelic variant c.1150T > C' had a typical achondroplasia (Ach phenotype. In addition, three other patients with atypical phenotypes showed no association with the allelic variant. Together, these results do not support the hypothesis of a modulatory role for the c.1150T > C change in the FGFR3 gene.

  14. Hypochondroplasia, Acanthosis Nigricans, and Insulin Resistance in a Child with FGFR3 Mutation: Is It Just an Association?

    Directory of Open Access Journals (Sweden)

    Manal Mustafa

    2014-01-01

    Full Text Available FGFR3 mutations cause wide spectrum of disorders ranging from skeletal dysplasias (hypochondroplasia, achondroplasia, and thanatophoric dysplasia, benign skin tumors (epidermal nevi, seborrhaeic keratosis, and acanthosis nigricans, and epithelial malignancies (multiple myeloma and prostate and bladder carcinoma. Hypochondroplasia is the most common type of short-limb dwarfism in children resulting from fibroblast growth factor receptor 3 (FGFR3 mutation. Acanthosis nigricans might be seen in severe skeletal dysplasia, including thanatophoric dysplasia and SADDAN syndrome, without a biochemical evidence of hyperinsulinemia. Insulin insensitivity and acanthosis nigricans are uncommonly seen in hypochondroplasia patients with FGFR3 mutations which may represent a new association. We aim to describe the association of hypochondroplasia, acanthosis nigricans, and insulin resistance in a child harboring FGFR3 mutation. To our knowledge, this is the first case report associating the p.N540 with acanthosis nigricans and the second to describe hyperinsulinemia in hypochondroplasia. This finding demonstrates the possible coexistence of insulin insensitivity and acanthosis nigricans in hypochondroplasia patients.

  15. A single nucleotide mutation in Nppc is associated with a long bone abnormality in lbab mice

    Directory of Open Access Journals (Sweden)

    Roe Bruce A

    2007-04-01

    Full Text Available Abstract Background The long bone abnormality (lbab mouse is a new autosomal recessive mutant characterized by overall smaller body size with proportionate dwarfing of all organs and shorter long bones. Previous linkage analysis has located the lbab mutation on chromosome 1 between the markers D1Mit9 and D1Mit488. Results A genome-based positional approach was used to identify a mutation associated with lbab disease. A total of 122 genes and expressed sequence tags at the lbab region were screened for possible mutation by using genomic DNA from lbabl/lbab, lbab/+, and +/+ B6 mice and high throughput temperature gradient capillary electrophoresis. A sequence difference was identified in one of the amplicons of gene Nppc between lbab/lbab and +/+ mice. One-step reverse transcriptase polymerase chain reaction was performed to validate the difference of Nppc in different types of mice at the mRNA level. The mutation of Nppc was unique in lbab/lbab mice among multiple mouse inbred strains. The mutation of Nppc is co-segregated with lbab disease in 200 progenies produced from heterozygous lbab/+ parents. Conclusion A single nucleotide mutation of Nppc is associated with dwarfism in lbab/lbab mice. Current genome information and technology allow us to efficiently identify single nucleotide mutations from roughly mapped disease loci. The lbab mouse is a useful model for hereditary human achondroplasia.

  16. Molecular, Phenotypic Aspects and Therapeutic Horizons of Rare Genetic Bone Disorders

    Directory of Open Access Journals (Sweden)

    Taha Faruqi

    2014-01-01

    Full Text Available A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, craniometaphyseal dysplasia, achondroplasia, and hypophosphatasia. The disease mechanisms of Gorham-Stout disease, melorheostosis, and multiple hereditary exostosis are not fully elucidated. Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP. The use of bisphosphonates and IL-6 inhibitors has been explored to be useful in the treatment of fibrous dysplasia, but more research is warranted. Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed. There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities.

  17. All Madelung deformities are not endocrine

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2013-01-01

    Full Text Available Madelung deformity is a rare inherited disorder associated with endocrine disorders like Turner′s syndrome, pseudohypoparathyroidism, but can be seen with short stature homeobox deficiency conditions such as Leri-Weill dyschondrosteosis (LWD and Langers mesomelic dysplasia. It has also been reported following trauma to the distal radius epiphysis neoplasia mucopolysaccharidosis (MPS and achondroplasia. Madelung deformity is an abnormality of distal radial epiphysis where in progressive ulnar and volar tilt of the articular surface occurring in association with distal subluxation of ulna. A 13-year-old girl was referred to us for evaluation of bilateral deformity of wrist and short stature. There was ulnar deviation and dorsal tilt of bilateral hands without history of pain to the joint trauma and family history of similar illness. On X-ray, wrist showed malformed distal radial epiphysis with dorsal and ulnar shift and with increased length of phalanges suggestive of Madelung deformity. X-ray spine was normal. Ultrasound abdomen showed normal uterus and ovary and her follicle stimulating hormone. Luteinizing hormone was normal and so was urine MPS screening. Based on the above points the diagnosis of LWD was made.

  18. Fibroblast Growth Factor Receptor 3 (FGFR3–Analyses of the S249C Mutation and Protein Expression in Primary Cervical Carcinomas

    Directory of Open Access Journals (Sweden)

    Haiyan Dai

    2001-01-01

    Full Text Available Fibroblast growth factor receptor 3 (FGFR3 seems to play an inhibitory role in bone development, as activating mutations in the gene underlie disorders such as achondroplasia and thanatophoric dysplasia. Findings from multiple myeloma (MM indicate that FGFR3 also can act as an oncogene, and mutation of codon 249 in the fibroblast growth factor receptor 3 (FGFR3 gene was recently detected in 3/12 primary cervical carcinomas. We have analysed 91 cervical carcinomas for this specific S249C mutation using amplification created restriction site methodology (ACRS, and detected no mutations. Immunohistochemistry was performed on 73 of the tumours. Reduced protein staining was seen in 43 (58.8% samples. Six of the tumours (8.2% revealed increased protein staining compared with normal cervical tissue. These patients had a better prognosis than those with reduced or normal levels, although not statistically significant. This report weakens the hypothesis of FGFR3 as an oncogene of importance in cervical carcinomas.

  19. The time of onset of abnormal calcification in spondylometaepiphyseal dysplasia, short limb-abnormal calcification type

    International Nuclear Information System (INIS)

    Tueysuez, Beyhan; Gazioglu, Nurperi; Uenguer, Savas; Aji, Dolly Yafet; Tuerkmen, Seval

    2009-01-01

    A 1-month-old boy with shortness of extremities on prenatal US was referred to our department with a provisional diagnosis of achondroplasia. His height was normal but he had short extremities and platyspondyly, premature carpal epiphyses on both hands, and short tubular bones with irregular metaphyses on radiographs. Re-evaluation of the patient at the age of 1 year revealed very short height and premature calcification of the costal cartilages and epiphyses. Spondylometaepiphyseal dysplasia (SMED), short limb-abnormal calcification type was diagnosed. This condition is a very rare autosomal recessively inherited disorder, and most of the patients die in early childhood due to neurological involvement. At the age of 2 years and 5 months, a CT scan showed narrowing of the cervical spinal canal. One month later he died suddenly because of spinal cord injury. In conclusion early diagnosis is very important because the recurrence risk is high and patients may die due to early neurological complications. The time of onset of abnormal calcifications, a diagnostic finding of the disease, is at the age of around 1 year in most patients. When abnormal calcifications are not yet present, but radiological changes associated with SMED are present, this rare disease must be considered. (orig.)

  20. Dwarfism and early death in mice lacking C-type natriuretic peptide

    Science.gov (United States)

    Chusho, Hideki; Tamura, Naohisa; Ogawa, Yoshihiro; Yasoda, Akihiro; Suda, Michio; Miyazawa, Takashi; Nakamura, Kenji; Nakao, Kazuki; Kurihara, Tatsuya; Komatsu, Yasato; Itoh, Hiroshi; Tanaka, Kiyoshi; Saito, Yoshihiko; Katsuki, Motoya; Nakao, Kazuwa

    2001-01-01

    Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc−/− mice). The Nppc−/− mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc−/− mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia. PMID:11259675

  1. Current insights into the molecular genetic basis of dwarfism in livestock.

    Science.gov (United States)

    Boegheim, Iris J M; Leegwater, Peter A J; van Lith, Hein A; Back, Willem

    2017-06-01

    Impairment of bone growth at a young age leads to dwarfism in adulthood. Dwarfism can be categorised as either proportionate, an overall size reduction without changes in body proportions, or disproportionate, a size reduction in one or more limbs, with changes in body proportions. Many forms of dwarfism are inherited and result from structural disruptions or disrupted signalling pathways. Hormonal disruptions are evident in Brooksville miniature Brahman cattle and Z-linked dwarfism in chickens, caused by mutations in GH1 and GHR. Furthermore, mutations in IHH are the underlying cause of creeper achondroplasia in chickens. Belgian blue cattle display proportionate dwarfism caused by a mutation in RNF11, while American Angus cattle dwarfism is caused by a mutation in PRKG2. Mutations in EVC2 are associated with dwarfism in Japanese brown cattle and Tyrolean grey cattle. Fleckvieh dwarfism is caused by mutations in the GON4L gene. Mutations in COL10A1 and COL2A1 cause dwarfism in pigs and Holstein cattle, both associated with structural disruptions, while several mutations in ACAN are associated with bulldog-type dwarfism in Dexter cattle and dwarfism in American miniature horses. In other equine breeds, such as Shetland ponies and Friesian horses, dwarfism is caused by mutations in SHOX and B4GALT7. In Texel sheep, chondrodysplasia is associated with a deletion in SLC13A1. This review discusses genes known to be involved in these and other forms of dwarfism in livestock. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism.

    Science.gov (United States)

    Wendt, Daniel J; Dvorak-Ewell, Melita; Bullens, Sherry; Lorget, Florence; Bell, Sean M; Peng, Jeff; Castillo, Sianna; Aoyagi-Scharber, Mika; O'Neill, Charles A; Krejci, Pavel; Wilcox, William R; Rimoin, David L; Bunting, Stuart

    2015-04-01

    Achondroplasia (ACH), the most common form of human dwarfism, is caused by an activating autosomal dominant mutation in the fibroblast growth factor receptor-3 gene. Genetic overexpression of C-type natriuretic peptide (CNP), a positive regulator of endochondral bone growth, prevents dwarfism in mouse models of ACH. However, administration of exogenous CNP is compromised by its rapid clearance in vivo through receptor-mediated and proteolytic pathways. Using in vitro approaches, we developed modified variants of human CNP, resistant to proteolytic degradation by neutral endopeptidase, that retain the ability to stimulate signaling downstream of the CNP receptor, natriuretic peptide receptor B. The variants tested in vivo demonstrated significantly longer serum half-lives than native CNP. Subcutaneous administration of one of these CNP variants (BMN 111) resulted in correction of the dwarfism phenotype in a mouse model of ACH and overgrowth of the axial and appendicular skeletons in wild-type mice without observable changes in trabecular and cortical bone architecture. Moreover, significant growth plate widening that translated into accelerated bone growth, at hemodynamically tolerable doses, was observed in juvenile cynomolgus monkeys that had received daily subcutaneous administrations of BMN 111. BMN 111 was well tolerated and represents a promising new approach for treatment of patients with ACH. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model.

    Science.gov (United States)

    Komla-Ebri, Davide; Dambroise, Emilie; Kramer, Ina; Benoist-Lasselin, Catherine; Kaci, Nabil; Le Gall, Cindy; Martin, Ludovic; Busca, Patricia; Barbault, Florent; Graus-Porta, Diana; Munnich, Arnold; Kneissel, Michaela; Di Rocco, Federico; Biosse-Duplan, Martin; Legeai-Mallet, Laurence

    2016-05-02

    Achondroplasia (ACH) is the most frequent form of dwarfism and is caused by gain-of-function mutations in the fibroblast growth factor receptor 3-encoding (FGFR3-encoding) gene. Although potential therapeutic strategies for ACH, which aim to reduce excessive FGFR3 activation, have emerged over many years, the use of tyrosine kinase inhibitor (TKI) to counteract FGFR3 hyperactivity has yet to be evaluated. Here, we have reported that the pan-FGFR TKI, NVP-BGJ398, reduces FGFR3 phosphorylation and corrects the abnormal femoral growth plate and calvaria in organ cultures from embryos of the Fgfr3Y367C/+ mouse model of ACH. Moreover, we demonstrated that a low dose of NVP-BGJ398, injected subcutaneously, was able to penetrate into the growth plate of Fgfr3Y367C/+ mice and modify its organization. Improvements to the axial and appendicular skeletons were noticeable after 10 days of treatment and were more extensive after 15 days of treatment that started from postnatal day 1. Low-dose NVP-BGJ398 treatment reduced intervertebral disc defects of lumbar vertebrae, loss of synchondroses, and foramen-magnum shape anomalies. NVP-BGJ398 inhibited FGFR3 downstream signaling pathways, including MAPK, SOX9, STAT1, and PLCγ, in the growth plates of Fgfr3Y367C/+ mice and in cultured chondrocyte models of ACH. Together, our data demonstrate that NVP-BGJ398 corrects pathological hallmarks of ACH and support TKIs as a potential therapeutic approach for ACH.

  4. A systematic review of genetic skeletal disorders reported in Chinese biomedical journals between 1978 and 2012

    Directory of Open Access Journals (Sweden)

    Cui Yazhou

    2012-08-01

    Full Text Available Abstract Little information is available on the prevalence, geographic distribution and mutation spectrum of genetic skeletal disorders (GSDs in China. This study systematically reviewed GSDs as defined in “Nosology and Classification of genetic skeletal disorders (2010 version” using Chinese biomedical literature published over the past 34 years from 1978 to 2012. In total, 16,099 GSDs have been reported. The most frequently reported disorders were Marfan syndrome, osteogenesis imperfecta, fibrous dysplasia, mucopolysaccharidosis, multiple cartilaginous exostoses, neurofibromatosis type 1 (NF1, osteopetrosis, achondroplasia, enchondromatosis (Ollier, and osteopoikilosis, accounting for 76.5% (12,312 cases of the total cases. Five groups (group 8, 12, 14, 18, 21 defined by “Nosology and Classification of genetic skeletal disorders” have not been reported in the Chinese biomedical literature. Gene mutation testing was performed in only a minor portion of the 16,099 cases of GSDs (187 cases, 1.16%. In total, 37 genes for 41 different GSDs were reported in Chinese biomedical literature, including 43 novel mutations. This review revealed a significant imbalance in rare disease identification in terms of geographic regions and hospital levels, suggesting the need to create a national multi-level network to meet the specific challenge of care for rare diseases in China.

  5. Percutaneous nephrolithotomy in ectopically located kidneys and in patients with musculoskeletal deformities.

    Science.gov (United States)

    Srivastava, A; Gupta, P; Chaturvedi, S; Singh, P; Kapoor, R; Dubey, D; Kumar, A

    2010-01-01

    To assess the feasibility, safety and results of percutaneous nephrolithotomy (PNL) in ectopically located kidneys and in patients with musculoskeletal deformities. Thirteen such patients underwent PNL between June 2005 and May 2008. Mean stone size was 27.4 mm (16-37 mm). Six patients had severe kyphoscoliosis, 2 patients each had achondroplasia, cross-fused ectopia and pelvic ectopic kidney, and 1 patient had thoracic kidney. All had a preoperative CT scan of the abdomen. Preoperative ultrasound- or CT-guided percutaneous nephrostomy (PCN) was done in 10 patients. Three patients underwent laparoscopic-assisted PNL. All underwent standard PNL. The stone-free rate, complication rate and need for secondary intervention were evaluated. PNL was successfully completed in all. A second ultrasound-guided intraoperative puncture was required in 2 patients. Re-look PNL was required in 1 patient and the same patient later required shock wave lithotripsy for complete stone clearance. The remaining 12 patients (92.3%) were rendered stone-free in a single sitting. PNL is a feasible and effective modality in anomalous kidneys. Preoperative planning with CT and image-guided PCN is helpful in these situations. Laparoscopic-assisted PNL can be safely performed in patients where access to a renal collecting system by fluoroscopy or image-guided assistance (ultrasound or CT scan) is not possible. Copyright (c) 2010 S. Karger AG, Basel.

  6. Anatomic Considerations for Radical Retropubic Prostatectomy in an Achondroplastic Dwarf

    Directory of Open Access Journals (Sweden)

    Dennis Gyomber

    2009-01-01

    Full Text Available This is the first report of a radical retropubic prostatectomy (RRP in an achondroplastic dwarf. We highlight the pelvic anatomy, precluding laparoscopic or robotic prostatectomy, and making open surgery extremely difficult. We review relevant literature regarding general, urological, and orthopedic abnormalities of achondroplasia (ACH and present a clinical case. No reports of RRP in achondroplastic dwarfs exist, with only one case of an abandoned RRP due to similar pelvic anatomy in a patient with osteogenesis imperfecta. Significant lumbar lordosis found in ACH results in a short anteroposterior dimension, severely limiting access to the prostate. We present a case of a 62-year-old achondroplastic dwarf who had Gleason 3+4 disease on transrectal ultrasound-guided biopsy in four from 12 cores. Surgery was difficult due to narrow anteroposterior pelvic dimension, but achievable. Histological analysis revealed multifocal prostate cancer, with negative surgical margins and no extraprostatic extension. RRP in ACH patients, although possible, should be approached with caution due to the abnormal pelvic dimensions, and discussions regarding potential abandonment of surgery should be included during informed consent. This case highlights the preoperative use of computed tomography to assist in the surgical planning for patients with difficult pelvic anatomy.

  7. Pseudoachondroplasia: A case report

    Directory of Open Access Journals (Sweden)

    Radlović Vladimir

    2013-01-01

    Full Text Available Introduction. Pseudoachondroplasia (PSACH is an autosomal dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein. It is characterized by rhizomelic dwarfism, limb and vertebral deformity, joint laxity and early onset osteoarthrosis. We present the girl with the early expressed and severe PSACH born to clinically and radiographically unaffected parents. Case Outline. A 6.5-year-old girl presented with short-limbed dwarfism (body height 79.5 cm, achondroplasia-like rhizomelic dwarfism recognized by the absence of abnormality at birth, normal craniofacial appearance, characteristic epiphyseal and metaphyseal radiographic finding and joint hyperlaxity.

  8. Delayed fatherhood.

    Science.gov (United States)

    Lawson, Gerald; Fletcher, Richard

    2014-10-01

    Birth data from developed countries indicates that the average paternal age is increasing. As the trend to older fatherhood has become established, concerns have been raised that this may be linked to adverse outcomes, such as pregnancy complications, congenital anomalies, and long-term health implications for the child. Since the sperm of older fathers may be impaired due to the general effects of ageing, their offspring may be at risk due to defects in sperm quality at conception. A literature search was performed to identify pregnancy complications, fetal anomalies and health issues for the child when the father is in an older age bracket. Evidence for impairment in the sperm and genetic material of older fathers was reviewed. With an older father, there is evidence of an increase in stillbirths and a slightly increased risk of autism, bipolar disorder and schizophrenia in the offspring later in life. The increased risk of achondroplasia has long been recognised. For the mother, there is an increased rate of Caesarean section. Investigations of other possible adverse outcomes have produced mixed findings. Further robust and longitudinal studies are needed to clarify these issues. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. Trabecular bone microarchitecture analysis, a way for an early detection of genetic dwarfism? Case study of a dwarf mother's offspring.

    Science.gov (United States)

    Colombo, Antony; Hoogland, Menno; Coqueugniot, Hélène; Dutour, Olivier; Waters-Rist, Andrea

    2018-03-01

    A 66 year-old woman with a disproportionate dwarfism and who bore seven children was discovered at the Middenbeemster archaeological site (The Netherlands). Three are perinates and show no macroscopic or radiological evidence for a FGFR3 mutation causing hypo-or achondroplasia. This mutation induces dysfunction of the growth cartilage, leading to abnormalities in the development of trabecular bone. Because the mutation is autosomal dominant, these perinates have a 50% risk of having been affected. This study determines whether trabecular bone microarchitecture (TBMA) analysis is useful for detecting genetic dwarfism. Proximal metaphyses of humeri were μCT-scanned with a resolution of 7-12 μm. Three volumes of interest were segmented from each bone with TIVMI© software. The TBMA was quantified in BoneJ© using six parameters on which a multivariate analysis was then performed. Two of the Middenbeemster perinates show a quantitatively different TBMA organization. These results and the family's medical history suggest a diagnosis of genetic dwarfism for this two perinates. This study provides evidence to support the efficacy of μCT for diagnosing early-stage bone disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Implementing Non-Invasive Prenatal Diagnosis (NIPD) in a National Health Service Laboratory; From Dominant to Recessive Disorders.

    Science.gov (United States)

    Drury, Suzanne; Mason, Sarah; McKay, Fiona; Lo, Kitty; Boustred, Christopher; Jenkins, Lucy; Chitty, Lyn S

    2016-01-01

    Our UK National Health Service regional genetics laboratory offers NIPD for autosomal dominant and de novo conditions (achondroplasia, thanataphoric dysplasia, Apert syndrome), paternal mutation exclusion for cystic fibrosis and a range of bespoke tests. NIPD avoids the risks associated with invasive testing, making prenatal diagnosis more accessible to families at high genetic risk. However, the challenge remains in offering definitive diagnosis for autosomal recessive diseases, which is complicated by the predominance of the maternal mutant allele in the cell-free DNA sample and thus requires a variety of different approaches. Validation and diagnostic implementation for NIPD of congenital adrenal hyperplasia (CAH) is further complicated by presence of a pseudogene that requires a different approach. We have used an assay targeting approximately 6700 heterozygous SNPs around the CAH gene (CYP21A2) to construct the high-risk parental haplotypes and tested this approach in five cases, showing that inheritance of the parental alleles can be correctly identified using NIPD. We are evaluating various measures of the fetal fraction to help determine inheritance of parental mutations. We are currently exploring the utility of an NIPD multi-disorder panel for autosomal recessive disease, to make testing more widely applicable to families with a variety of serious genetic conditions.

  11. A single nucleotide mutation in Nppc is associated with a long bone abnormality in lbab mice.

    Science.gov (United States)

    Jiao, Yan; Yan, Jian; Jiao, Feng; Yang, Hongbin; Donahue, Leah Rae; Li, Xinmin; Roe, Bruce A; Stuart, John; Gu, Weikuan

    2007-04-17

    The long bone abnormality (lbab) mouse is a new autosomal recessive mutant characterized by overall smaller body size with proportionate dwarfing of all organs and shorter long bones. Previous linkage analysis has located the lbab mutation on chromosome 1 between the markers D1Mit9 and D1Mit488. A genome-based positional approach was used to identify a mutation associated with lbab disease. A total of 122 genes and expressed sequence tags at the lbab region were screened for possible mutation by using genomic DNA from lbabl/lbab, lbab/+, and +/+ B6 mice and high throughput temperature gradient capillary electrophoresis. A sequence difference was identified in one of the amplicons of gene Nppc between lbab/lbab and +/+ mice. One-step reverse transcriptase polymerase chain reaction was performed to validate the difference of Nppc in different types of mice at the mRNA level. The mutation of Nppc was unique in lbab/lbab mice among multiple mouse inbred strains. The mutation of Nppc is co-segregated with lbab disease in 200 progenies produced from heterozygous lbab/+ parents. A single nucleotide mutation of Nppc is associated with dwarfism in lbab/lbab mice. Current genome information and technology allow us to efficiently identify single nucleotide mutations from roughly mapped disease loci. The lbab mouse is a useful model for hereditary human achondroplasia.

  12. New insight on FGFR3-related chondrodysplasias molecular physiopathology revealed by human chondrocyte gene expression profiling.

    Directory of Open Access Journals (Sweden)

    Laurent Schibler

    Full Text Available Endochondral ossification is the process by which the appendicular skeleton, facial bones, vertebrae and medial clavicles are formed and relies on the tight control of chondrocyte maturation. Fibroblast growth factor receptor (FGFR3 plays a role in bone development and maintenance and belongs to a family of proteins which differ in their ligand affinities and tissue distribution. Activating mutations of the FGFR3 gene lead to craniosynostosis and multiple types of skeletal dysplasia with varying degrees of severity: thanatophoric dysplasia (TD, achondroplasia and hypochondroplasia. Despite progress in the characterization of FGFR3-mediated regulation of cartilage development, many aspects remain unclear. The aim and the novelty of our study was to examine whole gene expression differences occurring in primary human chondrocytes isolated from normal cartilage or pathological cartilage from TD-affected fetuses, using Affymetrix technology. The phenotype of the primary cells was confirmed by the high expression of chondrocytic markers. Altered expression of genes associated with many cellular processes was observed, including cell growth and proliferation, cell cycle, cell adhesion, cell motility, metabolic pathways, signal transduction, cell cycle process and cell signaling. Most of the cell cycle process genes were down-regulated and consisted of genes involved in cell cycle progression, DNA biosynthesis, spindle dynamics and cytokinesis. About eight percent of all modulated genes were found to impact extracellular matrix (ECM structure and turnover, especially glycosaminoglycan (GAG and proteoglycan biosynthesis and sulfation. Altogether, the gene expression analyses provide new insight into the consequences of FGFR3 mutations in cell cycle regulation, onset of pre-hypertrophic differentiation and concomitant metabolism changes. Moreover, impaired motility and ECM properties may also provide clues about growth plate disorganization. These

  13. Selfish spermatogonial selection: evidence from an immunohistochemical screen in testes of elderly men.

    Directory of Open Access Journals (Sweden)

    Jasmine Lim

    Full Text Available The dominant congenital disorders Apert syndrome, achondroplasia and multiple endocrine neoplasia-caused by specific missense mutations in the FGFR2, FGFR3 and RET proteins respectively-represent classical examples of paternal age-effect mutation, a class that arises at particularly high frequencies in the sperm of older men. Previous analyses of DNA from randomly selected cadaveric testes showed that the levels of the corresponding FGFR2, FGFR3 and RET mutations exhibit very uneven spatial distributions, with localised hotspots surrounded by large mutation-negative areas. These studies imply that normal testes are mosaic for clusters of mutant cells: these clusters are predicted to have altered growth and signalling properties leading to their clonal expansion (selfish spermatogonial selection, but DNA extraction eliminates the possibility to study such processes at a tissue level. Using a panel of antibodies optimised for the detection of spermatocytic seminoma, a rare tumour of spermatogonial origin, we demonstrate that putative clonal events are frequent within normal testes of elderly men (mean age: 73.3 yrs and can be classed into two broad categories. We found numerous small (less than 200 cells cellular aggregations with distinct immunohistochemical characteristics, localised to a portion of the seminiferous tubule, which are of uncertain significance. However more infrequently we identified additional regions where entire seminiferous tubules had a circumferentially altered immunohistochemical appearance that extended through multiple serial sections that were physically contiguous (up to 1 mm in length, and exhibited enhanced staining for antibodies both to FGFR3 and a marker of downstream signal activation, pAKT. These findings support the concept that populations of spermatogonia in individual seminiferous tubules in the testes of older men are clonal mosaics with regard to their signalling properties and activation, thus fulfilling

  14. Volume reduction of the jugular foramina in Cavalier King Charles Spaniels with syringomyelia

    Directory of Open Access Journals (Sweden)

    Schmidt Martin

    2012-09-01

    Full Text Available Abstract Background Understanding the pathogenesis of the chiari-like malformation in the Cavalier King Charles Spaniel (CKCS is incomplete, and current hypotheses do not fully explain the development of syringomyelia (SM in the spinal cords of affected dogs. This study investigates an unconventional pathogenetic theory for the development of cerebrospinal fluid (CSF pressure waves in the subarachnoid space in CKCS with SM, by analogy with human diseases. In children with achondroplasia the shortening of the skull base can lead to a narrowing of the jugular foramina (JF between the cranial base synchondroses. This in turn has been reported to cause a congestion of the major venous outflow tracts of the skull and consequently to an increase in the intracranial pressure (ICP. Amongst brachycephalic dog breeds the CKCS has been identified as having an extremely short and wide braincase. A stenosis of the JF and a consequential vascular compromise in this opening could contribute to venous hypertension, raising ICP and causing CSF jets in the spinal subarachnoid space of the CKCS. In this study, JF volumes in CKCSs with and without SM were compared to assess a possible role of this pathologic mechanism in the development of SM in this breed. Results Computed tomography (CT scans of 40 CKCSs > 4 years of age were used to create three-dimensional (3D models of the skull and the JF. Weight matched groups (7–10 kg of 20 CKCSs with SM and 20 CKCSs without SM were compared. CKCSs without SM presented significantly larger JF -volumes (median left JF: 0.0633 cm3; median right JF: 0.0703 cm3; p 3; median right JF: 0.0434 cm3; p Conclusion A stenosis of the JF and consecutive venous congestion may explain the aetiology of CSF pressure waves in the subarachnoid space, independent of cerebellar herniation, as an additional pathogenetic factor for the development of SM in this breed.

  15. Delineation of facial archetypes by 3d averaging.

    Science.gov (United States)

    Shaweesh, Ashraf I; Thomas, C David L; Bankier, Agnes; Clement, John G

    2004-10-01

    The objective of this study was to investigate the feasibility of creating archetypal 3D faces through computerized 3D facial averaging. A 3D surface scanner Fiore and its software were used to acquire the 3D scans of the faces while 3D Rugle3 and locally-developed software generated the holistic facial averages. 3D facial averages were created from two ethnic groups; European and Japanese and from children with three previous genetic disorders; Williams syndrome, achondroplasia and Sotos syndrome as well as the normal control group. The method included averaging the corresponding depth (z) coordinates of the 3D facial scans. Compared with other face averaging techniques there was not any warping or filling in the spaces by interpolation; however, this facial average lacked colour information. The results showed that as few as 14 faces were sufficient to create an archetypal facial average. In turn this would make it practical to use face averaging as an identification tool in cases where it would be difficult to recruit a larger number of participants. In generating the average, correcting for size differences among faces was shown to adjust the average outlines of the facial features. It is assumed that 3D facial averaging would help in the identification of the ethnic status of persons whose identity may not be known with certainty. In clinical medicine, it would have a great potential for the diagnosis of syndromes with distinctive facial features. The system would also assist in the education of clinicians in the recognition and identification of such syndromes.

  16. Cellular evidence for selfish spermatogonial selection in aged human testes.

    Science.gov (United States)

    Maher, G J; Goriely, A; Wilkie, A O M

    2014-05-01

    Owing to a recent trend for delayed paternity, the genomic integrity of spermatozoa of older men has become a focus of increased interest. Older fathers are at higher risk for their children to be born with several monogenic conditions collectively termed paternal age effect (PAE) disorders, which include achondroplasia, Apert syndrome and Costello syndrome. These disorders are caused by specific mutations originating almost exclusively from the male germline, in genes encoding components of the tyrosine kinase receptor/RAS/MAPK signalling pathway. These particular mutations, occurring randomly during mitotic divisions of spermatogonial stem cells (SSCs), are predicted to confer a selective/growth advantage on the mutant SSC. This selective advantage leads to a clonal expansion of the mutant cells over time, which generates mutant spermatozoa at levels significantly above the background mutation rate. This phenomenon, termed selfish spermatogonial selection, is likely to occur in all men. In rare cases, probably because of additional mutational events, selfish spermatogonial selection may lead to spermatocytic seminoma. The studies that initially predicted the clonal nature of selfish spermatogonial selection were based on DNA analysis, rather than the visualization of mutant clones in intact testes. In a recent study that aimed to identify these clones directly, we stained serial sections of fixed testes for expression of melanoma antigen family A4 (MAGEA4), a marker of spermatogonia. A subset of seminiferous tubules with an appearance and distribution compatible with the predicted mutant clones were identified. In these tubules, termed 'immunopositive tubules', there is an increased density of spermatogonia positive for markers related to selfish selection (FGFR3) and SSC self-renewal (phosphorylated AKT). Here we detail the properties of the immunopositive tubules and how they relate to the predicted mutant clones, as well as discussing the utility of

  17. Detection of a de novo Y278C mutation in FGFR3 in a pregnancy with severe fetal hypochondroplasia: prenatal diagnosis and literature review.

    Science.gov (United States)

    Chen, Chih-Ping; Su, Yi-Ning; Lin, Tzu-Hung; Chang, Tung-Yao; Su, Jun-Wei; Wang, Wayseen

    2013-12-01

    We describe a prenatal molecular diagnosis of hypochondroplasia (HCH) in a pregnancy not at risk of HCH and review the literature on prenatal diagnosis of HCH. A 28-year-old primigravid woman was referred for genetic counseling at 30 weeks of gestation because of short-limbed dwarfism in the fetus. The woman had a body height of 152 cm. Her husband had a body height of 180 cm. Level II ultrasound showed a normal amount of amniotic fluid and a singleton fetus with fetal biometry equivalent to 30 weeks except for short limbs. Fetal biometry measurements were as follows: biparietal diameter = 7.38 cm (30 weeks); head circumference = 28.14 cm (30 weeks); abdominal circumference (AC) = 24.64 cm (30 weeks); femur length (FL) = 3.97 cm ( 0.18); humerus = 3.64 cm (diagnosis of achondroplasia (ACH) was made. DNA testing for the FGFR3 gene and whole-genome array comparative genomic hybridization (aCGH) analysis were performed using cord blood DNA obtained by cordocentesis. FGFR3 mutation analysis revealed a de novo heterozygous c.833A > G, TAC > TGC transversion in exon 7 leading to a p.Tyr278Cys (Y278C) mutation in the FGFR3 protein. aCGH analysis revealed no genomic imbalance in cord blood. After delivery, the fetus had short limbs, a narrow thorax, brachydactyly, and relative macrocephaly. Cytogenetic analysis of cultured placental cells revealed a karyotype of 46,XX. Prenatal diagnosis of abnormal ultrasound findings suspicious of ACH should include a differential diagnosis of HCH by molecular analysis of FGFR3. Copyright © 2013. Published by Elsevier B.V.

  18. Volume reduction of the jugular foramina in Cavalier King Charles Spaniels with syringomyelia.

    Science.gov (United States)

    Schmidt, Martin Jürgen; Ondreka, Nele; Sauerbrey, Maren; Volk, Holger Andreas; Rummel, Christoph; Kramer, Martin

    2012-09-06

    Understanding the pathogenesis of the chiari-like malformation in the Cavalier King Charles Spaniel (CKCS) is incomplete, and current hypotheses do not fully explain the development of syringomyelia (SM) in the spinal cords of affected dogs. This study investigates an unconventional pathogenetic theory for the development of cerebrospinal fluid (CSF) pressure waves in the subarachnoid space in CKCS with SM, by analogy with human diseases. In children with achondroplasia the shortening of the skull base can lead to a narrowing of the jugular foramina (JF) between the cranial base synchondroses. This in turn has been reported to cause a congestion of the major venous outflow tracts of the skull and consequently to an increase in the intracranial pressure (ICP). Amongst brachycephalic dog breeds the CKCS has been identified as having an extremely short and wide braincase. A stenosis of the JF and a consequential vascular compromise in this opening could contribute to venous hypertension, raising ICP and causing CSF jets in the spinal subarachnoid space of the CKCS. In this study, JF volumes in CKCSs with and without SM were compared to assess a possible role of this pathologic mechanism in the development of SM in this breed. Computed tomography (CT) scans of 40 CKCSs > 4 years of age were used to create three-dimensional (3D) models of the skull and the JF. Weight matched groups (7-10 kg) of 20 CKCSs with SM and 20 CKCSs without SM were compared. CKCSs without SM presented significantly larger JF -volumes (median left JF: 0.0633 cm3; median right JF: 0.0703 cm3; p stenosis of the JF and consecutive venous congestion may explain the aetiology of CSF pressure waves in the subarachnoid space, independent of cerebellar herniation, as an additional pathogenetic factor for the development of SM in this breed.

  19. Dwarfs in ancient Egypt.

    Science.gov (United States)

    Kozma, Chahira

    2006-02-15

    Ancient Egypt was one of the most advanced and productive civilizations in antiquity, spanning 3000 years before the "Christian" era. Ancient Egyptians built colossal temples and magnificent tombs to honor their gods and religious leaders. Their hieroglyphic language, system of organization, and recording of events give contemporary researchers insights into their daily activities. Based on the record left by their art, the ancient Egyptians documented the presence of dwarfs in almost every facet of life. Due to the hot dry climate and natural and artificial mummification, Egypt is a major source of information on achondroplasia in the old world. The remains of dwarfs are abundant and include complete and partial skeletons. Dwarfs were employed as personal attendants, animal tenders, jewelers, and entertainers. Several high-ranking dwarfs especially from the Old Kingdom (2700-2190 BCE) achieved important status and had lavish burial places close to the pyramids. Their costly tombs in the royal cemeteries and the inscriptions on their statutes indicate their high-ranking position in Egyptian society and their close relation to the king. Some of them were Seneb, Pereniankh, Khnumhotpe, and Djeder. There were at least two dwarf gods, Ptah and Bes. The god Ptah was associated with regeneration and rejuvenation. The god Bes was a protector of sexuality, childbirth, women, and children. He was a favored deity particularly during the Greco-Roman period. His temple was recently excavated in the Baharia oasis in the middle of Egypt. The burial sites and artistic sources provide glimpses of the positions of dwarfs in daily life in ancient Egypt. Dwarfs were accepted in ancient Egypt; their recorded daily activities suggest assimilation into daily life, and their disorder was not shown as a physical handicap. Wisdom writings and moral teachings in ancient Egypt commanded respect for dwarfs and other individuals with disabilities. Copyright (c) 2005 Wiley-Liss, Inc.

  20. Genetic drift. The ancient Egyptian dwarfs of the pyramids: the high official and the female worker.

    Science.gov (United States)

    Kozma, Chahira; Sarry El Din, Azza Mohamed; El Shafy El Banna, Rokia Abd; El Samie Kandeel, Wafaa Abd; Lachman, Ralph

    2011-08-01

    The existence of dwarfism is amply documented in ancient Egypt due to the rich biological and artistic legacies. In previous articles published in this journal, I discussed the roles of people with skeletal dysplasia in ancient Egyptian civilization. In this article I, along with my Egyptian and American colleagues, describe two skeletons of dwarfs that date to 2700-2184 BCE and were unearthed from a funerary complex near the Great Pyramids in Giza. The first skeleton belongs to a high official, Per-ni-ankh-w, who died between 45 and 50 years of age. His statue is on display in the Egyptian Museum of Cairo. The second skeleton belongs to a pregnant female worker found with a fetus in situ. Her estimated age at death was 25-30 years. She most likely died during childbirth due to a small pelvic outlet as supported by her narrow sacrum. The fetal bones appear normal. Radiological examination of both skeletons confirmed the clinical diagnosis of achondroplasia. Ancient Egyptians concerned themselves with the search for spiritual fulfillment through the tradition of moral teachings. Amenemope, a wise man who lived during the reign of Amenhotep III (1391-1354 BCE), advocated respect toward individuals with disabilities: Do not jeer at a blind man nor tease a dwarf, Neither interfere with the condition of a cripple. Do not taunt a man who is in the hand of God, Nor scowl at him if he errs. In summary, artistic, biological, and written resources indicate that dwarfs were well integrated in ancient Egyptian society. Copyright © 2011 Wiley-Liss, Inc.

  1. Anestesia em anã acondroplásica obesa mórbida para gastroplastia redutora Anestesia en enana acondroplásica obesa mórbida para gastroplastia reductora Anesthesia for bariatric surgery in an achondroplastic dwarf with morbid obesity

    Directory of Open Access Journals (Sweden)

    Maria Angélica Abrão

    2009-02-01

    í la conducción de la anestesia.BACKGROUND AND OBJECTIVES: Achondroplasia is the most common form among the different types of osteochondrodysplasia that cause dwarfism. Dwarves develop obesity quite frequently, and surgical treatment has shown greater efficacy, both for effective weight loss and long term maintenance. The objective of this report was to present the case of bariatric surgery with Y-en-Roux gastric bypass in an achondroplastic dwarf with morbid obesity. The different difficulties in the anesthetic management of this patient and the way they were dealt with were discussed in order to decrease intraoperative morbidity and mortality. CASE REPORT: This is a 29 years old female dwarf with achondroplasia and morbid obesity since childhood. She was 123 cm tall and weighed 144 kg at the time of admission to the Bariatric Surgery service. With a body mass index (BMI of 95.18 kg.m-2, she had several associated diseases especially of the respiratory system and osteoarticular system. After a long follow-up with diet, exercises, and psychological support, her clinical condition improved and she was referred for surgery: Y-en-Roux gastroplasty using the technique of Capella-Fobi. Intubation of the awake patient under direct laryngoscopy was difficult and a bronchofibroscope had to be used. Surgery was uneventful and the patient was maintained under total intravenous anesthesia with continuous infusion of remifentanil and propofol. She was extubated at the end of the surgery still in the operating room. CONCLUSIONS: The simultaneous comorbidities of achondroplasia and morbid obesity can hinder the anesthetic management, especially regarding the airways. A thorough pre-anesthetic evaluation is necessary to anticipate the conducts and minimize risks, therefore optimizing the evolution of anesthesia.

  2. Seqüestro pulmonar extralobar: análise anatomopatológica de dois casos em natimortos e revisão da literatura Extralobar pulmonary sequestration: anatomical analysis of two cases in stillbirths and review of literature

    Directory of Open Access Journals (Sweden)

    Ítalo Martins de Oliveira

    2008-06-01

    Full Text Available O seqüestro pulmonar é definido como uma massa anormal de tecido pulmonar sem comunicação com a árvore brônquica. É anomalia rara, responsável por 0,15-6,45% das malformações pulmonares congênitas. Quando possui revestimento pleural próprio, chama-se seqüestro pulmonar extralobar (SPE. Este trabalho descreve dois casos de SPE em natimortos (NM com 32 (1 e 34 (2 semanas de gestação com diagnóstico clínico de hipoxia intra-uterina e adenomatose cística, respectivamente, e faz revisão da literatura. O diagnóstico envolveu análise ultra-sonográfica, sindrômica, macroscópica e microscópica dos NM. Foi observada massa supradiafragmática no hemitórax esquerdo ligada à aorta torácica (1 e ao diafragma (2. As MFs associadas foram agenesia tímica (2, hipoplasia pulmonar (2, pé torto congênito (1 e acondroplasia de membros (2. A microscopia evidenciou, nos dois casos, tecido pulmonar imaturo e pedículo vascularizado e inervado.Pulmonary sequestration represents an abnormal pulmonary mass that does not communicate with the tracheobronchial tree. It is a rare malformation (MF, accountable for 0.15%-6.45% of pulmonary congenital MFs. When it has its own pleural covering, it is called extralobar (EBPS. This work describes two cases of EBPS in stillbirths (SB, at 32 (1 and 34 (2 weeks' gestation, with clinical diagnosis of intrauterine hypoxia and cystic adenomatosis, respectively. It also reviews the literature on the subject. The diagnosis involved ultrasonographic, syndromic, macroscopic and microscopic analysis. The macroscopy showed a supradiaphragmatic mass in the left hemithorax linked to thoracic aorta (1 and diaphragm (2. The associated MFs were: thymic agenesis (2, pulmonary hypoplasia (2, clubfoot (1 and achondroplasia (2. Microscopy demonstrated, in both cases, immature pulmonary tissue and vascularized and innervated pedicle.

  3. Caracterización patogénica de los recién nacidos con malformaciones múltiples

    Directory of Open Access Journals (Sweden)

    Francisca Alonso Lotti

    1998-06-01

    Full Text Available El Registro Cubano de Malformaciones Congénitas (RECUMAC ha analizado 520 578 recién nacidos en 36 hospitales ginecobstétricos de 13 provincias de Cuba en un período de 12 años (de marzo de 1985 a diciembre de 1996, en el cual la prevalencia de malformaciones congénitas al nacimiento es de 179,8 por 10 000 nacimientos. El 24,6 % de los casos presentó 2 ó más malformaciones asociadas entre sí. Se realizó la clasificación de los multimalformados y los síndromes resultaron ser los más frecuentes. Entre los cromosómicos, el síndrome de Down ocupó el primer lugar, con una prevalencia al nacimiento de 7,8 por 10 000 nacimientos. En relación con los monogénicos heredados con modelos autosómicos dominante y recesivo la acondroplasia y el albinismo presentaron el mayor número de casos para una prevalencia al nacimiento de 0,44 y 0,21 por 10 000 nacimientos, respectivamente.The Cuban Registry of Congenital Malformations (CRCM has analyzed 520 578 newborns at 36 gynecobstetric hospitals in 13 provinces af Cuba for 12 years (from March, 1985 to December, 1996, in which the prevalence of malformations at birth is of 179.8 per 10 000 births. 24.6 % of the cases presented 2 or more malformations associated among themselves. The classification of those suffering from multimalformation was carried out and syndromes proved to be the most frequent. Within the cromosomic syndromes the Down´s syndrome was in the first place with a prevalence at birth of 7.8 per 10 000 births´. In connection with monogenic syndromes inherited with dominant and recessive autosomal models, achondroplasia and albinism had the highest number of cases for a prevalence at birth of 0.44 and 0.21 per 10 000 births, respectively.

  4. [Short stature treatment by lower limb lengthening--multicenter study from five centers].

    Science.gov (United States)

    Koczewski, Paweł; Shadi, Milud; Napiontek, Marek; Dorman, T; Faflik, J; Grzegorzewski, A; Jasiewicz, B; Kacki, W; Kucharski, R; Niedzielski, K; Synder, M; Tesiorowski, M; Zarzycka, M; Zarek, S

    2002-01-01

    26 patients (17 female, 9 male) from 5 centers were evaluated. The age at the beginning of treatment ranged from 6 to 29 years (mean 13.8). The cause of short stature in 19 patients was achondroplasia or pseudoachondroplasia, in next 2--other bone dysplasias. The other 5 patients had not bone pathology and were treated because of cosmetic indications. Preoperative body height ranged from 90 to 149 cm (mean 120). Axial deviations of the lower extremities were noted in 11 patients. Mean follow-up was 3.7 years. METHOD OF TREATMENT: Most of patients were treated with Ilizarov device using cross lengthening strategy (2 stages--opposite femur and tibia lengthening). Mean duration of treatment including interval between two stages (mean 12 months) was 29 months. Planned increase of body height ranged from 10 to 26 cm (mean 16.4). Planned or greater lengthening (mean 14.8 cm) was achieved in 14 patients. Partial planned lengthening (mean 65% of planned lengthening) was achieved in 8 patients (mean 11.8 cm) including two patients who resigned the second stage of treatment. In two patients lengthening was stopped during first month of treatment because of great complications. In 2 patients treatment was not completed (interval between first and second stage). Mean increase of body height of patients with complete treatment was 13.1 cm (from 2 to 28). Problems, obstacles and complications were analyzed according to Paley classification. There were 24 problems in 15 patient (inflammation process around K wires--15 patients, bone healing disturbances--3, regenerate fracture--2, transient foot equinus--2 and axial deviation of the lower extremity--1). There were 31 obstacles in 19 patients (regenerate's defect--7 patients, premature bone consolidation--6, foot equinus--4 and other--14). There were 26 complications in 18 patients (axial deviation of the lengthened segment--8, foot equinus--6, paresis of the peroneal nerve--3, fractures--2 and other--5). The most serious

  5. Estudo comparativo do nível de qualidade de vida entre sujeitos acondroplásicos e não-acondroplásicos Comparative study of quality of life level between achondroplasics and non-achondroplasics subjects

    Directory of Open Access Journals (Sweden)

    Mariana Pereira Cervan

    2008-01-01

    Full Text Available A acondroplasia é caracterizada como um distúrbio genético autossômico dominante que afeta a ossificação endocondral, constituindo uma das causas de nanismo. Entre as características está presente principalmente a baixa estatura e desproporção tronco/membros. Diante disso, o acondroplásico poderá se mostrar inferiorizado e insatisfeito com sua aparência física, influenciando, juntamente a outros fatores, na qualidade de vida (QV dessa população. OBJETIVO: Comparar o nível de QV entre sujeitos acondroplásicos e não-acondroplásicos. MÉTODO: Foram avaliados 21 indivíduos acondroplásicos, sendo nove homens e 13 mulheres, pareados por idade e gênero, a 21 não-acondroplásicos. O nível de QV foi estimado por meio do questionário WHOQOL-BREF. RESULTADOS: Na comparação entre sujeitos acondroplásicos e não acondroplásicos do gênero feminino constatou-se que no domínio físico as mulheres acondroplásicas apresentaram escore médio significativamente menor, enquanto na comparação entre os gêneros, o grupo de mulheres acondroplásicas apresentou escore médio significativamente menor que os homens acondroplásicos no domínio psicológico. CONCLUSÃO: No presente estudo, a QV não apresentou diferença entre os grupos, entretanto, nos domínios físico e psicológico, as mulheres acondroplásicas demonstraram menor satisfação com sua condição.Achondroplasia is characterized as an autosomal dominant genetic disturbance which affects the endochondral ossification which is a common cause of dwarfism syndrome. Among the characteristics the most common are the short stature and disproportional trunk/limbs. Thus, the achondroplasic subjects can face themselves inferior and not satisfied with their physical appearance, influencing, among other factors, the quality of life of this population. OBJECTIVE: To compare the quality of life level between achondroplasic and non-achondroplasic subjects. METHODS: Study with 21

  6. Desbalance redox en la infertilidad masculina Lack of Redox balance in male sterility

    Directory of Open Access Journals (Sweden)

    Akel Mallok

    2011-06-01

    between generation of reactive oxygen species and the antioxidants that may to cause damages or deformities in the spermatozoa and eventually male sterility. The reactive oxygen species are produced due to different mechanisms present in semen, motionless spermatozoa or with motility disorders, leukocytes and morphologically normal spermatozoa but functionally abnormal. Among these damages it is present the lipid peroxidation to spermatic membrane and the nuclear and mitochondrial DNA fragmentation. The damages of oxidative stress on DNA may also to cause disorders in offspring including cancer and achondroplasia. Lipid peroxidation leads to an alteration in the membrane affecting its structure and function. The human spermatozoon membrane contains a high proportion of poly-non-saturated fatty acids therefore its oversensitivity to lipid peroxidation is very high. The reactive oxygen species have different effects on spermatic cells, being a very controversial topic. The aim of present paper was to update readers on some of the biochemical features related to the production of reactive oxygen species and the diagnostic methods used to detect the human sterility.

  7. From Horus the child to Hephaestus who limps: a romp through history.

    Science.gov (United States)

    Aterman, K

    1999-03-05

    The question of why Hephaestus, the Greek god of smiths, limped has been the subject of much debate, mainly on mythological grounds. This debate extended also into the field of medical diagnosis, with attempts at defining the nature of the deformity that made the crippled Hephaestus the buffoon of the other Olympic gods. One problem encountered in these debates was the changes to which the ugly young Hephaestus was subjected with the passing of time-from a limping deformed youth to the later dignified and normal man. While some authors, largely influenced by poetic Greek texts and vase paintings, attributed the limp to talipes (club-feet), others pointed to certain features suggestive of achondroplasia. Since the image of the early Hephaestus is based mainly on the much earlier concept of the Egyptian god Ptah, who as the triune god of the resurrection sometimes is depicted as an achondroplastic dwarf (Ptah-Pataikos), the suggestion of the possible achondroplastic dwarf-like nature of the early Hephaestus is not implausible. It is supported by similarities in the image of Hephaestus to some features in other Egyptian gods, such as the domestic god Bes, the guardian of the new-born, and the Horus the Child or Harpocrates (Greek), yet another protector of youth and "the symbol of everything that is young and vigorous" [Budge, 1969: The Gods of the Egyptians, or Studies in Egyptian Mythology. Volume I.]. The characteristic feature of this child-god is the "lock of Harpocrates" on the right side of his head. That this lock can sometimes also be seen not only on the head of Ptah-Pataikos and of Bes but also on the young Hephaestus is highly suggestive of the Egyptian influence on his image. Recently, however, another interesting explanation of Hephaestus's limp has been suggested that may explain why the Egyptian influenced image of the early achondroplastic Hephaestus changed to the later, more Grecian view of the smith-god who hobbled because of club

  8. MANAGEMENT OF LUMBAR SPINAL CANAL STENOSIS

    Directory of Open Access Journals (Sweden)

    Mukhergee G. S

    2016-06-01

    Full Text Available BACKGROUND Spinal stenosis is one of the most common conditions in the elderly. It is defined as a narrowing of the spinal canal. The term stenosis is derived from the Greek word for narrow, which is “Stenos”. The first description of this condition is attributed to Antoine portal in 1803. Verbiest is credited with coining the term spinal stenosis and the associated narrowing of the spinal canal as its potential cause. [1-10] Kirkaldy–Willis subsequently described the degenerative cascade in the lumbar spine as the cause for the altered anatomy and pathophysiology in spinal stenosis. [11-15] If compression does not occur, the canal should be described as narrow but not stenotic. Some studies defined lumbar spinal stenosis as a “narrowing of the osteoligamentous vertebral canal and/or the intervertebral foramina causing compression of the thecal sac and/or the caudal nerve roots; at a single vertebral level, narrowing may affect the whole canal or part of it” (Postacchini 1983. This definition distinguished between disc herniation and stenosis. [16] . The most common type of spinal stenosis is caused by degenerative arthritis of the spine. Hypertrophy and ossification of the posterior longitudinal ligament which usually are confined to the cervical spine, and diffuse idiopathic skeletal hyperostosis (DISH syndrome also may result in an acquired form of spinal stenosis. Congenital forms caused by disorders such as achondroplasia and dysplastic spondylolisthesis are much less common. Congenital spinal stenosis usually is central and is evident or imaging studies. Idiopathic congenital narrowing usually involves the anteroposterior dimension of the canal secondary to short pedicles; the patient otherwise is normal. In contrast, in achondroplasia, the canal is narrowed in the anteroposterior plane owing to shortened pedicles and in lateral dimension because of diminished interpedicular distance. Acquired forms of spinal stenosis usually are

  9. Bloqueio bilateral do nervo pudendo para hemorroidectomia em paciente acondroplásico: relato de caso Bloqueo bilateral del nervio pudendo para hemorroidectomía en paciente acondroplásico: relato de caso Bilateral blockade of the pudend nerve to hemorrhoidectomy in achondroplasic patient: case report

    Directory of Open Access Journals (Sweden)

    Bruno Salomé de Morais

    2006-04-01

    ética espontánea. La anestesia de esos pacientes presenta varias particularidades. El objetivo del presente relato fue el de describir un caso de paciente acondroplásico, con previo historial de intervención quirúrgica de la columna para descompresión medular, sometido a Hemorroidectomía a través de bloqueo bilateral de los nervios pudendos. RELATO DEL CASO: Paciente del sexo masculino, 47 años, acondroplásico, que fue ingresado para la realización de hemorroidectomía.Al hacérsele el examen físico presentaba el cuello acortado con extensión limitada de la cabeza, Mallampati clase IV, distancia tireomentoniana de 6 cm y abertura de la boca de 3,5 cm. La columna vertebral presentaba cifosis torácica y lordosis lumbar acentuada, además de cicatriz quirúrgica en la región lumbar. Fue realizado el bloqueo bilateral de los nervios pudendos con ropivacaina a 1%, por vía transperineal, con una aguja aislada de 0,8 mm x 100 mm 21G (Stimuplex A100 BBraun, Melsungen, Germany conectada al estimulador de nervios periféricos (Stimuplex-DIG, BBraun.El paciente fue colocado en decúbito ventral y la cirugía iniciada después de 15 minutos da administración del anestésico. Durante todo el procedimiento, el paciente permaneció consciente y no relató ningún dolor o incomodidad. Hasta el momento del alta hospitalaria (22h después de la realización del bloqueo, el paciente no refirió dolor, incomodidad, náusea, vómito, bloqueo motor, retención o incontinencia urinaria. Después del alta, evolucionó bien presentando evacuación después de 31 horas de efectuada la cirugía. CONCLUSIONES: El caso mostró el uso del bloqueo bilateral de los nervios pudendos, con el auxilio del neuroestimulador como técnica anestésica aislada para la hemorroidectomía.BACKGROUND AND OBJECTIVES: The achondroplasic dwarfism or achondroplasia is the most common form of dwarfism and occurs, in most of the cases, as a result of spontaneous genetic alteration. The anesthesia in these