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Cited by 121Muscle Physiology and DisordersGenomics and Rare DiseasesGenetics and Neurodevelopmental Disorders

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Facioscapulohumeral Muscular Dystrophy

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Statland, Jeffrey M., Tawil, Rabi·2016·Continuum
DOI 10.1212/con.0000000000000399PMC PMC5898965
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Abstract

PURPOSE OF REVIEW: This article describes the clinical characteristics, diagnosis, molecular pathogenesis, and treatment of facioscapulohumeral muscular dystrophy (FSHD). RECENT FINDINGS: FSHD comprises two genetically distinct types that converge on a common downstream pathway of the expression of the toxic protein DUX4. Approximately 95% of patients have FSHD type 1 (FSHD1), in which loss of DNA repetitive elements (D4Z4 repeats) in the subtelomeric region of chromosome 4q causes decreased methylation and epigenetic derepression of DUX4, a gene contained within each D4Z4 repeat. FSHD type 2 (FSHD2) occurs through a deletion-independent mechanism but, similar to FSHD1, leads to decreased methylation and epigenetic derepression in the same region of chromosome 4q. Whereas FSHD1 is dominantly inherited, FSHD2 shows digenic inheritance, and about 80% of patients will have a mutation in the SMCHD1 gene. DUX4 lacks a polyadenylation signal, so both FSHD1 and FSHD2 only occur in the presence of permissive 4q polymorphisms, which provide a stabilizing polyadenylation sequence. FSHD is an epigenetic disease, and penetrance and severity are related to both the number of residual D4Z4 units and D4Z4 methylation. SUMMARY: Recent consensus guidelines outline standards for care for FSHD, and identification of potential therapeutic targets have shifted emphasis in the research community toward drug development and clinical trial planning.

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Metadata

Authors
Statland, J. M., & Tawil, R.
Affiliations
University of Rochester Medicine (US)
Corresponding author
Tawil, Rabi
ORCID
Venue
Continuum
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2016-12
Volume
22
Issue
6
Pages
1916-1931
ISSN
  • 1080-2371 (ISSN-L)
  • 1538-6899
DOI
10.1212/con.0000000000000399
PMC
PMC5898965
OpenAlex
W2559821780
Cited by
121
References
2
Citations by year
2026: 15 · 2025: 10 · 2024: 11 · 2023: 12 · 2022: 15 · 2021: 17 · 2020: 16 · 2019: 17 · 2018: 6 · 2017: 2
FWCI
4.33
Type
journal article
Language
en
Open access
Locations
  • CONTINUUM Lifelong Learning in Neurology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Bristol-Myers Squibb
  • Novartis
  • FSH Society
  • Friends of FSH Research
  • Acceleron
  • aTyr
  • Sarepta Therapeutics
  • National Institutes of Health (KL2TR000119)
  • National Institute of Neurological Disorders and Stroke (P01NS069539, U01NS061795)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54AR065139)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
facioscapulohumeral muscular dystrophy, FSHD1, FSHD2, DUX4, D4Z4 repeat, chromosome 4q, epigenetic derepression, DNA methylation, SMCHD1, digenic inheritance, polyadenylation, molecular pathogenesis, diagnosis, treatment, clinical guidelines
MeSH terms
Adolescent, Adult, Humans, Male, Pedigree, Muscular Dystrophy, Facioscapulohumeral

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