The Limb-Girdle Muscular Dystrophies and the Dystrophinopathies

Stanley Jones P. Iyadurai, MSc, PhD, MD; John T. Kissel, MD, FAAN Muscle and Neuromuscular Junction Disorders p. 1954-1977 December 2016, Vol.22, No.6 doi: 10.1212/CON.0000000000000406
Article as PDF
-- Select an option --

Purpose of Review: The classic approach to identifying and accurately diagnosing limb-girdle muscular dystrophies (LGMDs) relied heavily on phenotypic characterization and ancillary studies including muscle biopsy. Because of rapid advances in genetic sequencing methodologies, several additional LGMDs have been molecularly characterized, and the diagnostic approach to these disorders has been simplified. This article summarizes the epidemiology, clinical features, and genetic defects underlying the LGMDs.

Recent Findings: In recent years, the advent of next-generation sequencing has heralded an era of molecular diagnosis in conjunction with physical characterization. Inadvertently, this process has also led to the “next-generation aftermath,” whereby variants of unknown significance are identified in most patients. Similar to the published diagnostic and treatment guidelines for Duchenne muscular dystrophy, diagnostic and treatment guidelines have recently been published for LGMDs. In addition, the first medication (based on the exon-skipping strategy) for treatment of patients with a subset of Duchenne muscular dystrophy has been recently approved by the US Food and Drug Administration (FDA).

Summary: The LGMDs are a heterogeneous group of hereditary, progressive, and degenerative neuromuscular disorders that present with primary symptoms of shoulder girdle and pelvic girdle weakness. Although a combination of clinical and molecular genetic evaluations may be sufficient for accurate diagnosis of LGMDs in many cases, the contribution of imaging and histopathologic correlations still remains a critical, if not a necessary, component of evaluation in some cases.

Address correspondence to Dr Stanley Jones P. Iyadurai, Ohio State University, Wexner Medical Center, Department of Neurology, 395 W 12th Ave, Columbus, OH 43210, [email protected].

Relationship Disclosure: Dr Iyadurai has received personal compensation for serving on the advisory boards of Allergan; Alnylam Pharmaceuticals, Inc; CSL Behring; and Pfizer, Inc. Dr Kissel has received personal compensation for serving on a consulting board of AveXis, Inc; as journal editor of Muscle & Nerve; and as a consultant for Novartis AG. Dr Kissel has received research/grant funding as principal investigator of a study from the National Institutes of Health and has received funding for clinical trials from AveXis, Inc; AxelaCare Health Solutions, LLC; BioMarin; CSL Behring; Cytokinetics, Inc; Ionis Pharmaceuticals; and Quintiles, Inc; and receives publishing royalties from Oxford University Press.

Unlabeled Use of Products/Investigational Use Disclosure: Drs Iyadurai and Kissel discuss the unlabeled/investigational use of corticosteroids to treat Duchenne muscular dystrophy.

Supplemental digital content: Videos accompanying this article are cited in the text as Supplemental Digital Content. Videos may be accessed by clicking on links provided in the HTML, PDF, and app versions of this article; the URLs are provided in the print version. Video legends begin on page 1976.

Copyright © 2016 by the American Academy of Neurology.