Premium
The phenotype of the musculocontractural type of Ehlers‐Danlos syndrome due to CHST14 mutations
Author(s) -
Janecke Andreas R.,
Li Ben,
Boehm Manfred,
Krabichler Birgit,
Rohrbach Marianne,
Müller Thomas,
Fuchs Irene,
Golas Gretchen,
Katagiri Yasuhiro,
Ziegler Shira G.,
Gahl William A.,
Wilnai Yael,
Zoppi Nicoletta,
Geller Herbert M.,
Giunta Cecilia,
Slavotinek Anne,
Steinmann Beat
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37383
Subject(s) - ehlers–danlos syndrome , decorin , medicine , joint hypermobility , dermatan sulfate , fulminant , pathology , heparan sulfate , anatomy , cartilage , heparin , proteoglycan
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. © 2015 Wiley Periodicals, Inc.