Clinical and molecular features of 66 patients with musculocontractural Ehlers-Danlos syndrome caused by pathogenic variants in

Abnormalities, Multiple / genetics Ehlers-Danlos Syndrome / diagnosis Female Genetic Association Studies Humans Male Phenotype Sulfotransferases / genetics
human genetics musculoskeletal diseases

Journal

Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R

Informations de publication

Date de publication:
Sep 2022
Historique:
received: 29 11 2020
accepted: 25 09 2021
pubmed: 25 11 2021
medline: 24 8 2022
entrez: 24 11 2021
Statut: ppublish

Résumé

Musculocontractural Ehlers-Danlos syndrome is caused by biallelic loss-of-function variants in We collected detailed and comprehensive clinical and molecular information regarding previously reported and newly identified patients with mcEDS- 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- This first international collaborative study of mcEDS-

Sections du résumé

BACKGROUND
Musculocontractural Ehlers-Danlos syndrome is caused by biallelic loss-of-function variants in
METHODS
We collected detailed and comprehensive clinical and molecular information regarding previously reported and newly identified patients with mcEDS-
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-
CONCLUSION
This first international collaborative study of mcEDS-

Identifiants

DOI: 10.1136/jmedgenet-2020-107623 PMID: 34815299 PMC: PMC9411915
pubmed: 34815299
pii: jmedgenet-2020-107623
doi: 10.1136/jmedgenet-2020-107623
pmc: PMC9411915
doi:

Substances chimiques

Sulfotransferases EC 2.8.2.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

865-877

Informations de copyright

© 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.

Déclaration de conflit d'intérêts

Competing interests: None declared.

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Auteurs

Mari Minatogawa (M)

Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
Center for Medical Genetics, Shinshu University Hospital, Matsumoto, Japan.

Ai 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.

Hiroko Morisaki (H)

Department of Medical Genetics, Sakakibara Heart Institute, Tokyo, Japan.
Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Suita, Japan.

Delfien Syx (D)

Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.

Tohru Sonoda (T)

Department of Occupational Therapy, School of Health and Science, Kyushu University of Health and Welfare, Nobeoka, Japan.

Andreas R Janecke (AR)

Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria.
Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.

Anne Slavotinek (A)

Division of Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0001-7053-2449

Nicol C Voermans (NC)

Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Centre, Nijmegen, The Netherlands.

Yves 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.

Roberto Mendoza-Londono (R)

Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.

Klaas J Wierenga (KJ)

Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, USA.

Parul Jayakar (P)

Division of Genetics and Metabolism, Nicklaus Children's Hospital, Miami, FL, USA.

William A 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.

Cynthia J 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.

Luis E Figuera (LE)

División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Mexico.

Yvonne Hilhorst-Hofstee (Y)

Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.

Alessandra Maugeri (A)

Department of Clinical Genetics, VU University Medical Centre Amsterdam, Amsterdam, The Netherlands.

Ken Ishikawa (K)

Department of Pediatrics, Iwate Medical University, Morioka, Japan.

Tomoko 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.

Yoko Aoki (Y)

Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.

Toshihiro Ohura (T)

Division of Clinical Laboratory, Sendai City Hospital, Sendai, Japan.

Hiroshi 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.

Michihiro 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.

Kosuke Mochida (K)

Department of Dermatology, University of Miyazaki Faculty of Medicine, Miyazaki, Japan.

Chiho Tokorodani (C)

Department of Pediatrics, Kochi Health Sciences Center, Kochi, Japan.

Kiyoshi Kikkawa (K)

Department of Pediatrics, Kochi Health Sciences Center, Kochi, Japan.

Takayuki 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.

Tetsuyuki Kobayashi (T)

Department of Internal Medicine, Nagano Chuo Hospital, Nagano, Japan.

Takaya Nakane (T)

Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Chuo, Japan.

Akiharu Kubo (A)

Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.

Judith D Ranells (JD)

Department of Pediatrics, University of South Florida, College of Medicine, Tampa, FL, USA.

Ohsuke Migita (O)

Department of Clinical Genetics, St. Marianna University, School of Medicine, Kawasaki, Japan.

Glenda Sobey (G)

EDS National Diagnostic Service, Sheffield Children's Hospital, Sheffield, UK.

Anupriya Kaur (A)

Department of Pediatrics (Genetics Division), Advanced Pediatric Cente, Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India.

Masumi Ishikawa (M)

Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
Center for Medical Genetics, Shinshu University Hospital, Matsumoto, Japan.

Tomomi 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.

Naomichi Matsumoto (N)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
ORCID: 0000-0001-9846-6500

Fransiska Malfait (F)

Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.

Noriko Miyake (N)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Tomoki 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.
ORCID: 0000-0002-8344-7507

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Classifications MeSH

questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Malformations › Malformations multiples › Clinical and molecular features of 66 patients...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies génétiques de la peau › Syndrome d'Ehlers-Danlos › Clinical and molecular features of 66 patients...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Études d'associations génétiques › Clinical and molecular features of 66 patients...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Clinical and molecular features of 66 patients...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Clinical and molecular features of 66 patients...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Sulfur group transferases › Sulfotransferases › Clinical and molecular features of 66 patients...