Facioscapulohumeral Muscular Dystrophies

Kathryn R. Wagner, MD, PhD Muscle and Neuromuscular Junction Disorders p. 1662-1681 December 2019, Vol.25, No.6 doi: 10.1212/CON.0000000000000801
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PURPOSE OF REVIEW Facioscapulohumeral muscular dystrophy (FSHD) is a common muscular dystrophy affecting both pediatric and adult patients. This article reviews the phenotype and pathophysiology of the disease as well as the recent efforts in clinical outcome measures and clinical trials.

RECENT FINDINGS As the name implies, FSHD involves weakness of facial muscles, muscles that fix the scapula, and muscles overlying the humerus (biceps and triceps). The distinctive phenotype of FSHD occurs secondary to two different genetic mechanisms. FSHD type 1 (FSHD1) is due to a deletion on chromosome 4q, leading to hypomethylation and derepression of DUX4. FSHD type 2 (FSHD2) is due to mutations in SMCHD1 with resulting hypomethylation of the same subtelomeric region of chromosome 4q and derepression of DUX4. Understanding the central role of DUX4 has opened up the possibility of disease-modifying treatments. In preparation for clinical trials of novel agents, researchers are in the process of validating a number of clinical trial outcome measures including MRI, the 6-minute walk test, the FSHD Composite Outcome Measure, reachable workspace, electrical impedance myography, and the FSHD Health Index.

SUMMARY The treatment of FSHD is currently supportive only. While past clinical trials in FSHD have been largely disappointing, novel agents in development, including antisense oligonucleotides, gene therapy, and small molecules, hold promise for future meaningful therapies.

Address correspondence to Dr Kathryn R. Wagner, Center for Genetic Muscle Disorders, Kennedy Krieger Institute, 707 N Broadway, Baltimore, MD 21205, wagnerk@kennedykrieger.org.

RELATIONSHIP DISCLOSURE: Dr Wagner has received personal compensation for serving on the data safety monitoring board of FibroGen, Inc; the dose escalation committee of Wave Pharma; and as a consultant for Asklepios BioPharmaceutical, Inc, Dynacure, F. Hoffmann-La Roche AG, PTC Therapeutics, and Sarepta Therapeutics. Dr Wagner has received research/grant support from Acceleron Pharma, Inc; Catabasis; F. Hoffmann-La Roche AG; Fulcrum Therapeutics; Michael’s Cause; the National Institute of Child Health and Human Development; Pfizer Inc; Pietro’s Fight; and Ryan’s Quest.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Dr Wagner reports no disclosure.

© 2019 American Academy of Neurology.