Clinical and molecular features of 66 patients with musculocontractural Ehlers-Danlos syndrome caused by pathogenic variants in CHST14 (mcEDS- CHST14 ).

Autor:	Minatogawa M; Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.; Center for Medical Genetics, Shinshu University Hospital, Matsumoto, Japan., Unzaki A; Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.; Center for Medical Genetics, Shinshu University Hospital, Matsumoto, Japan.; Problem-Solving Oriented Training Program for Advanced Medical Personnel: NGSD (Next Generation Super Doctor) Project, Matsumoto, Japan., Morisaki H; Department of Medical Genetics, Sakakibara Heart Institute, Tokyo, Japan.; Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Suita, Japan., Syx D; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium., Sonoda T; Department of Occupational Therapy, School of Health and Science, Kyushu University of Health and Welfare, Nobeoka, Japan., Janecke AR; Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria.; Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria., Slavotinek A; Division of Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA., Voermans NC; Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Centre, Nijmegen, The Netherlands., Lacassie Y; Department of Pediatrics, Louisiana State University Health Science Center, New Orleans, LA, USA.; Division of Clinical Genetics and Department of Genetics, Children's Hospital of New Orleans, New Orleans, LA, USA., Mendoza-Londono R; Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada., Wierenga KJ; Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, USA., Jayakar P; Division of Genetics and Metabolism, Nicklaus Children's Hospital, Miami, FL, USA., Gahl WA; Undiagnosed Diseases Program, Office of the NIH Director, National Institutes of Health, Bethesda, MD, USA.; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Tifft CJ; Undiagnosed Diseases Program, Office of the NIH Director, National Institutes of Health, Bethesda, MD, USA.; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Figuera LE; División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Mexico., Hilhorst-Hofstee Y; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands., Maugeri A; Department of Clinical Genetics, VU University Medical Centre Amsterdam, Amsterdam, The Netherlands., Ishikawa K; Department of Pediatrics, Iwate Medical University, Morioka, Japan., Kobayashi T; Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.; Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.; Graduate School of Medicine, Tohoku University, Senda, Japan., Aoki Y; Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan., Ohura T; Division of Clinical Laboratory, Sendai City Hospital, Sendai, Japan., Kawame H; Division of Genomic Medicine Support and Genetic Counseling, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.; Miyagi Children's Hospital, Sendai, Japan.; Division of Clinical Genetics, Jikei University Hospital, Tokyo, Japan., Kono M; Department of Dermatology, Nagoya University Graduate School of Medicine Faculty of Medicine, Nagoya, Japan.; Department of Dermatology and Plastic Surgery, Akita University Graduate School of Medicine School of Medicine, Akita, Akita, Japan., Mochida K; Department of Dermatology, University of Miyazaki Faculty of Medicine, Miyazaki, Japan., Tokorodani C; Department of Pediatrics, Kochi Health Sciences Center, Kochi, Japan., Kikkawa K; Department of Pediatrics, Kochi Health Sciences Center, Kochi, Japan., Morisaki T; Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Suita, Japan.; Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.; Department of Internal Medicine, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Kobayashi T; Department of Internal Medicine, Nagano Chuo Hospital, Nagano, Japan., Nakane T; Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Chuo, Japan., Kubo A; Department of Dermatology, Keio University School of Medicine, Tokyo, Japan., Ranells JD; Department of Pediatrics, University of South Florida, College of Medicine, Tampa, FL, USA., Migita O; Department of Clinical Genetics, St. Marianna University, School of Medicine, Kawasaki, Japan., Sobey G; EDS National Diagnostic Service, Sheffield Children's Hospital, Sheffield, UK., Kaur A; Department of Pediatrics (Genetics Division), Advanced Pediatric Cente, Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India., Ishikawa M; Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.; Center for Medical Genetics, Shinshu University Hospital, Matsumoto, Japan., Yamaguchi T; Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.; Center for Medical Genetics, Shinshu University Hospital, Matsumoto, Japan.; Division of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto, Japan., Matsumoto N; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Malfait F; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium., Miyake N; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Kosho T; Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan ktomoki@shinshu-u.ac.jp.; Center for Medical Genetics, Shinshu University Hospital, Matsumoto, Japan.; Division of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto, Japan.; Research Center for Supports to Advanced Science, Shinshu University, Matsumoto, Japan.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2022 Sep; Vol. 59 (9), pp. 865-877. Date of Electronic Publication: 2021 Nov 23.
DOI:	10.1136/jmedgenet-2020-107623
Abstrakt:	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 (>90%). Large subcutaneous haematomas, constipation, cryptorchidism, hypotonia and motor developmental delay were also common (>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. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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