RT Journal Article
SR Electronic
T1 Clinical and molecular features of 66 patients with musculocontractural Ehlers−Danlos syndrome caused by pathogenic variants in <em>CHST14</em> (mcEDS-<em>CHST14</em>)
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP jmedgenet-2020-107623
DO 10.1136/jmedgenet-2020-107623
A1 Mari Minatogawa
A1 Ai Unzaki
A1 Hiroko Morisaki
A1 Delfien Syx
A1 Tohru Sonoda
A1 Andreas R Janecke
A1 Anne Slavotinek
A1 Nicol C Voermans
A1 Yves Lacassie
A1 Roberto Mendoza-Londono
A1 Klaas J Wierenga
A1 Parul Jayakar
A1 William A Gahl
A1 Cynthia J Tifft
A1 Luis E Figuera
A1 Yvonne Hilhorst-Hofstee
A1 Alessandra Maugeri
A1 Ken Ishikawa
A1 Tomoko Kobayashi
A1 Yoko Aoki
A1 Toshihiro Ohura
A1 Hiroshi Kawame
A1 Michihiro Kono
A1 Kosuke Mochida
A1 Chiho Tokorodani
A1 Kiyoshi Kikkawa
A1 Takayuki Morisaki
A1 Tetsuyuki Kobayashi
A1 Takaya Nakane
A1 Akiharu Kubo
A1 Judith D Ranells
A1 Ohsuke Migita
A1 Glenda Sobey
A1 Anupriya Kaur
A1 Masumi Ishikawa
A1 Tomomi Yamaguchi
A1 Naomichi Matsumoto
A1 Fransiska Malfait
A1 Noriko Miyake
A1 Tomoki Kosho
YR 2021
UL http://jmg.bmj.com/content/early/2021/11/22/jmedgenet-2020-107623.abstract
AB Background Musculocontractural Ehlers−Danlos syndrome is caused by biallelic loss-of-function variants in CHST14 (mcEDS-CHST14) or DSE (mcEDS-DSE). Although 48 patients in 33 families with mcEDS-CHST14 have been reported, the spectrum of pathogenic variants, accurate prevalence of various manifestations and detailed natural history have not been systematically investigated.Methods We collected detailed and comprehensive clinical and molecular information regarding previously reported and newly identified patients with mcEDS-CHST14 through international collaborations.Results Sixty-six patients in 48 families (33 males/females; 0–59 years), including 18 newly reported patients, were evaluated. Japanese was the predominant ethnicity (27 families), associated with three recurrent variants. No apparent genotype–phenotype correlation was noted. Specific craniofacial (large fontanelle with delayed closure, downslanting palpebral fissures and hypertelorism), skeletal (characteristic finger morphologies, joint hypermobility, multiple congenital contractures, progressive talipes deformities and recurrent joint dislocation), cutaneous (hyperextensibility, fine/acrogeria-like/wrinkling palmar creases and bruisability) and ocular (refractive errors) features were observed in most patients (&gt;90%). Large subcutaneous haematomas, constipation, cryptorchidism, hypotonia and motor developmental delay were also common (&gt;80%). Median ages at the initial episode of dislocation or large subcutaneous haematoma were both 6 years. Nine patients died; their median age was 12 years. Several features, including joint and skin characteristics (hypermobility/extensibility and fragility), were significantly more frequent in patients with mcEDS-CHST14 than in eight reported patients with mcEDS-DSE.Conclusion This first international collaborative study of mcEDS-CHST14 demonstrated that the subtype represents a multisystem disorder with unique set of clinical phenotypes consisting of multiple malformations and progressive fragility-related manifestations; these require lifelong, multidisciplinary healthcare approaches.Data are available upon reasonable request.