학술논문

The phenotype of the musculocontractural type of Ehlers‐Danlos syndrome due to CHST14 mutations
Document Type
article
Source
American Journal of Medical Genetics Part A. 170(1)
Subject
Biomedical and Clinical Sciences
Ophthalmology and Optometry
Rare Diseases
Brain Disorders
Clinical Research
Pediatric
Adolescent
Adult
Child
Child
Preschool
Connective Tissue Diseases
Dermis
Ehlers-Danlos Syndrome
Female
Fibroblasts
Fluorescent Antibody Technique
Indirect
Humans
Infant
Male
Middle Aged
Mutation
Sulfotransferases
Young Adult
dermatan sulfate
deficiency
dermatan sulfate epimerase
N-acetylgalactosamine 4-O-sulfotransferase
connective tissue
Ehlers-Danlos syndrome
adducted thumb
clubfoot
proteoglycan
arthrogryposis
myopathy
Genetics
Clinical Sciences
Clinical sciences
Language
Abstract
The musculocontractural type of Ehlers-Danlos syndrome (MC-EDS) has been recently recognized as a clinical entity. MC-EDS represents a differential diagnosis within the congenital neuromuscular and connective tissue disorders spectrum. Thirty-one and three patients have been reported with MC-EDS so far with bi-allelic mutations identified in CHST14 and DSE, respectively, encoding two enzymes necessary for dermatan sulfate (DS) biosynthesis. We report seven additional patients with MC-EDS from four unrelated families, including the follow-up of a sib-pair originally reported with the kyphoscoliotic type of EDS in 1975. Brachycephaly, a characteristic facial appearance, an asthenic build, hyperextensible and bruisable skin, tapering fingers, instability of large joints, and recurrent formation of large subcutaneous hematomas are always present. Three of seven patients had mildly elevated serum creatine kinase. The oldest patient was blind due to retinal detachment at 45 years and died at 59 years from intracranial bleeding; her affected brother died at 28 years from fulminant endocarditis. All patients in this series harbored homozygous, predicted loss-of-function CHST14 mutations. Indeed, DS was not detectable in fibroblasts from two unrelated patients with homozygous mutations. Patient fibroblasts produced higher amounts of chondroitin sulfate, showed intracellular retention of collagen types I and III, and lacked decorin and thrombospondin fibrils compared with control. A great proportion of collagen fibrils were not integrated into fibers, and fiber bundles were dispersed into the ground substance in one patient, all of which is likely to contribute to the clinical phenotype. This report should increase awareness for MC-EDS.