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Ryoikibetsu Shokogun Shirizu 2001
Review
Topics: Abnormalities, Multiple; Dysostoses; Forehead; Humans; Nose
PubMed: 11462369
DOI: No ID Found -
American Journal of Medical Genetics.... Nov 2009Ellis-van Creveld syndrome (EvC; OMIM 225500) is a recessive disorder comprising chondrodysplasia, polydactyly, nail dysplasia, orofacial abnormalities and, in a... (Review)
Review
Ellis-van Creveld syndrome (EvC; OMIM 225500) is a recessive disorder comprising chondrodysplasia, polydactyly, nail dysplasia, orofacial abnormalities and, in a proportion of patients, cardiovascular malformations. Weyers acrodental dysostosis (Weyers; OMIM 193530) is an allelic dominant disorder comprising polydactyly, nail dysplasia, and orofacial abnormalities. EvC results from loss-of-function mutations in EVC or EVC2, the phenotype associated with the mutations in these two genes being indistinguishable. Three convincing causative mutations have been identified in patients with Weyers acrodental dysostosis, which are clustered in the last coding exon of EVC2 and lead to production of a truncated protein lacking the final 43 amino acids. Localization and function of EVC and EVC2 are inferred from studying the murine orthologs. Both Evc and Evc2 proteins localize to the basal bodies of primary cilia and analysis of an Ellis-van Creveld mouse model, which includes the limb shortening and tooth abnormalities of EvC patients, has demonstrated Hedgehog signaling defects in the absence of Evc. The loss of Evc2 has not been studied directly, but Hedgehog signaling is impaired when a mutant murine Evc2 Weyer variant is expressed in vitro. We conclude that the phenotypic abnormalities in EvC and Weyers syndrome result from tissue specific disruption of the response to Hh ligands.
Topics: Animals; Cilia; Dysostoses; Ellis-Van Creveld Syndrome; Exons; Female; Genes, Recessive; Genotype; Hedgehog Proteins; Humans; Ligands; Male; Mice; Models, Biological; Mutation; Phenotype; Radiography
PubMed: 19876929
DOI: 10.1002/ajmg.c.30226 -
Biologie Aujourd'hui 2016Acrodysostosis refers to a heterogeneous group of rare skeletal dysplasia that share characteristic features including severe brachydactyly, facial dysostosis and nasal... (Review)
Review
Acrodysostosis refers to a heterogeneous group of rare skeletal dysplasia that share characteristic features including severe brachydactyly, facial dysostosis and nasal hypoplasia. The literature describing acrodysostosis cases has been confusing because some reported patients may have had other phenotypically related diseases presenting Albright Hereditary Osteodystrophy (AHO) such as pseudohypoparathyroidism type 1a (PHP1a) or pseudopseudohypoparathyroidism (PPHP). A question has been whether patients display or not abnormal mineral metabolism associated with resistance to PTH and/or resistance to other hormones that bind G-protein coupled receptors (GPCR) linked to Gsa, as observed in PHP1a. Defects in two genes, PRKAR1A and PDE4D, both important players in the GPCR-Gsa-cAMP-PKA signaling, were recently identified in patients affected with acrodysostosis. This has helped clarify some issues regarding the heterogeneity of acrodysostosis, in particular the presence of hormonal resistance. Two different genetic and phenotypic syndromes are now identified, both with a similar bone dysplasia: acrodysostosis type 1 due to PRKAR1A defects, and acrodysostosis type 2, due to PDE4D defects. The existence of hormone resistance is typical of the acrodysostosis type 1 syndrome. We discuss here the PRKAR1A and PDE4D gene defects and phenotypes identified in acrodysostosis syndromes, in particular in regard to phenotypically related diseases caused by Gsa gene defects in the same signaling pathway.
Topics: Cyclic AMP; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; Cyclic Nucleotide Phosphodiesterases, Type 4; Drug Resistance; Dysostoses; Hormones; Humans; Intellectual Disability; Mutation; Osteochondrodysplasias; Pseudohypoparathyroidism; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 27813477
DOI: 10.1051/jbio/2016018 -
Ugeskrift For Laeger Sep 2001Fibroblast growth factors are structurally related proteins associated with cell growth, differentiation, migration, wound healing, angiogenesis, and oncogenesis. At the... (Review)
Review
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 genes encoding fibroblast growth factor receptors have been identified, and mutations in three of these, FGFR1, FGFR2, and FGFR3, can cause different congenital, autosomal dominant disorders affecting the craniofacial and skeletal development: craniosynostosis and chondrodysplasias. The craniosynostosis syndromes: Apert syndrome, Beare-Stevenson syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Muenke syndrome, Pfeiffer syndrome and Saethre-Chotzen syndrome can be caused by mutation in either FGFR1, FGFR2, or FGFR3. Saethre-Chotzen syndrome can also be caused by mutation in a functionally related gene, 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.
Topics: Bone Diseases, Developmental; Craniosynostoses; Dysostoses; Gene Expression Regulation, Developmental; Humans; Mutation; Radiography; Receptors, Fibroblast Growth Factor; Syndrome
PubMed: 11571861
DOI: No ID Found -
Modern Problems in Ophthalmology 1975
Topics: Animals; Craniofacial Dysostosis; Craniosynostoses; Diseases in Twins; Female; Genes, Dominant; Genes, Recessive; Male; Mandibulofacial Dysostosis; Pedigree; Polymorphism, Genetic
PubMed: 1177916
DOI: No ID Found -
American Journal of Medical Genetics.... Jul 2003We report two consecutive Caucasian male siblings of nonconsanguineous parents autopsied at 22 and 13 weeks gestational age both with prenatal diagnosis of Jarcho-Levin... (Review)
Review
We report two consecutive Caucasian male siblings of nonconsanguineous parents autopsied at 22 and 13 weeks gestational age both with prenatal diagnosis of Jarcho-Levin syndrome (JLS). Segmentation anomalies of the vertebrae and ribs encompass a spectrum of syndromes with or without associated anomalies of other developmental fields, and include spondylothoracic dysostosis (STD), JLS, Casamassima-Morton-Nance (CMN) syndrome, and spondylocostal dysostosis (SCD), among others. In both these new JLS cases the autopsies confirmed that there were severe developmental alterations in the thoracic and vertebral skeleton (including "crab-like" thorax), accompanied in the older fetus by renal defects. Because vertebral development is controlled by a limited number of master genes including Pax1 and Pax9, we analyzed protein expression from these genes in these two cases compared to age-matched controls. Immunochemical analysis showed a significant reduction in levels of Pax1 and Pax9 protein expression in chondrocytes of the vertebral column. Implications for the etiology and pathogenesis of JLS and related disorders are discussed.
Topics: Abnormalities, Multiple; Adult; DNA-Binding Proteins; Dysostoses; Female; Fetal Death; Humans; Kidney; Male; Musculoskeletal Abnormalities; Osteochondrodysplasias; Pedigree; Pregnancy; Radiography; Siblings; Syndrome; Thoracic Vertebrae; Ultrasonography, Prenatal
PubMed: 12833407
DOI: 10.1002/ajmg.a.20192 -
Hormones (Athens, Greece) 2013An 18-year-old man was admitted to the clinic complaining of deterioration in the function of his hands and feet. The clinical examination revealed that his movements...
An 18-year-old man was admitted to the clinic complaining of deterioration in the function of his hands and feet. The clinical examination revealed that his movements were clumsy and that he had disproportionally short limbs. In addition, he also had facial abnormalities of frontal bossing, hypertelorism, maxillary hypoplasia, broad low nasal bridge, short upturned nose with anteverted nostrils and triangular mouth. All extremities appeared short with stubby fingers and toes and with broad hands and wrinkling of the dorsal skin. Chromosomal analysis showed a normal (46, XY) karyotype. X-ray studies revealed broad, short metacarpals and phalanges with cone-shaped epiphyses and brachycdactyly and a diagnosis of peripheral dysostosis was confirmed by the characteristic radiographic appearance of the hands. Serum calcium and alkaline phosphatase levels were high, parathormone (PTH) was low, but 25 (OH) Vitamin D, albumin, and 24 hour urine calcium levels were in the normal range. Based on these findings, a diagnosis of acrodysostosis associated with hypercalcemia was made. To the best of our knowledge, this represents the first description of this syndrome.
Topics: Adolescent; Ataxia; Diagnosis, Differential; Dysostoses; Hand Bones; Humans; Hypercalcemia; Intellectual Disability; Male; Osteochondrodysplasias; Pseudohypoparathyroidism; Radiography
PubMed: 23933701
DOI: 10.14310/horm.2002.1416 -
Spine Jul 2004Prospective assessment of a cohort of patients affected by spondylocostal dysostosis. (Review)
Review
STUDY DESIGN
Prospective assessment of a cohort of patients affected by spondylocostal dysostosis.
OBJECTIVE
To report on the results of conservative and operative management of spondylocostal dysostosis and, based on this, to propose an assessment and treatment protocol for the condition.
SUMMARY OF BACKGROUND DATA
Spondylocostal dysostosis and spondylothoracic dysostosis are subtypes of Jarcho-Levin syndrome, a hereditary condition manifested by vertebral body and related rib malformations. Mortality prevails in spondylothoracic dysostosis because of more severe respiratory compromise.
METHODS
Details of prenatal and postnatal diagnosis, history, and management of 13 patients with spondylocostal dysostosis are presented. All patients were treated postnatally with repeated chest physiotherapy. Two patients refractory to conservative treatment underwent surgical intervention: the first had a chest wall reconstruction via a latissimus dorsi flap, the second a posterior spinal instrumented fusion for progressive scoliosis.
RESULTS
Prenatal ultrasound in 4 of 13 cases showed full details of vertebral and rib anomalies. Thoracic and lumbar hemivertebrae were most common, leading to congenital scoliosis in 10 of 13 cases. A number of extraskeletal abnormalities were also identified. At an average follow-up of 4.5 years, the survival rate was 100% with a remarkable decrease of the rate of respiratory complications. Surgical treatment in selected cases led to satisfactory results.
CONCLUSIONS
Prenatal diagnosis of spondylocostal dysostosis allows exclusion of spondylothoracic dysostosis and aids genetic counseling in quantifying the risk to siblings. Postnatally, prompt management of these patients with physiotherapy leads to prolonged survival. Surgical intervention may then be indicated to stabilize chest wall or spine deformities, with promising results.
Topics: Abnormalities, Multiple; Antibiotic Prophylaxis; Braces; Child; Child, Preschool; Cohort Studies; Combined Modality Therapy; Consanguinity; Disease Progression; Dysostoses; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Physical Therapy Modalities; Prospective Studies; Respiration Disorders; Respiratory Tract Infections; Ribs; Scoliosis; Spinal Fusion; Spine; Treatment Outcome; Ultrasonography, Prenatal
PubMed: 15223937
DOI: 10.1097/01.brs.0000128761.72844.ab -
Indian Journal of Pediatrics 1992
Review
Topics: Adolescent; Adult; Caloric Tests; Child; Child, Preschool; Dysostoses; Ear, External; Ear, Middle; Female; Hearing Disorders; Humans; Infant; Infant, Newborn; Male
PubMed: 1459686
DOI: 10.1007/BF02833004 -
Annales de Chirurgie Plastique Et... Oct 2001
Topics: Ear, External; Humans; Mandibulofacial Dysostosis; Preoperative Care; Plastic Surgery Procedures
PubMed: 11770464
DOI: 10.1016/s0294-1260(01)00063-2