Facioscapulohumeral muscular dystrophy

Handbook of Clinical Neurology
Rabi Tawil

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy with a distinctive pattern of skeletal muscle weakness and a wide spectrum of disease severity. The pathophysiologic consequences of the genetic lesion, the loss of a critical number of macrosatellite repeats (D4Z4) in the subtelomeric region of chromosome 4q35, remained unexplained for almost two decades. Recent studies demonstrate that contraction in the number of D4Z4 repeats results in chromatin relaxation and transcriptional de-repression of DUX4, a gene normally expressed only in the germline. In about 5% of individuals with phenotypic FSHD, there is no contraction in the D4Z4 repeats and yet similar chromatin changes are present, resulting in the inappropriate expression of the DUX4 gene. The chromatin changes in this form of FSHD (FSHD2) are the result, in most cases, of mutations in SMCHD1, a gene on chromosome 18 involved in chromatin regulation. The recent identification of aberrant activation of DUX4 transcription in FSHD as the root cause of FSHD now allows for a targeted approach to therapeutic development.

Citations

Jan 26, 2020·International Journal of Molecular Sciences·Kenji Rowel Q LimToshifumi Yokota
Jul 23, 2020·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·Giulia GiacomucciGiorgio Tasca
Mar 8, 2020·Neurology. Neuroimmunology and Neuroinflammation·Xavier Suárez-CalvetJordi Díaz-Manera
May 14, 2020·Annals of Neurology·A Reghan FoleyCarsten G Bönnemann
Mar 2, 2021·European Journal of Applied Physiology·Matteo Beretta-PiccoliGiuseppe D'Antona
Jun 3, 2021·Medicina·Elisabeta BădilăAlexandru Scafa Udriște
Jun 17, 2021·Muscle & Nerve·Stefan NicolauTeerin Liewluck
Jul 6, 2021·Frontiers in Physiology·Matteo Beretta-PiccoliGiuseppe D'Antona
Jul 29, 2021·Current Heart Failure Reports·Edyta BlaszczykJeanette Schulz-Menger
Sep 21, 2021·Brain : a Journal of Neurology·Natalie K KatzJeffrey M Statland

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