The Limb-Girdle Muscular Dystrophies

Matthew P. Wicklund, MD, FAAN Muscle and Neuromuscular Junction Disorders p. 1599-1618 December 2019, Vol.25, No.6 doi: 10.1212/CON.0000000000000809
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purpose of review As a group, the limb-girdle muscular dystrophies (LGMDs) are the fourth most prevalent genetic muscle disease, yet they are still not well known or understood. This article defines and describes LGMDs, delineates a diagnostic strategy, and discusses treatment of the LGMDs.

recent findings In 2018, the definition of the LGMDs was further refined, and a new nomenclature was proposed. Diagnosis of the LGMDs was long guided by the distinctive clinical characteristics of each particular subtype but now integrates use of genetics—with next-generation sequencing panels, exomes, and full genome analysis—early in the diagnostic assessment. Appreciation of the phenotypic diversity of each LGMD subtype continues to expand. This emphasizes the need for precision genetic diagnostics to better understand each subtype and formulate appropriate management for individual patients. Of significant relevance, the explosion of research into therapeutic options accentuates the need for accurate diagnosis, comprehensive disease characterization, and description of the natural histories of the LGMDs to move the field forward and to mitigate disease impact on patients with LGMD.

summary The LGMDs are genetic muscle diseases that superficially appear similar to one another but have important differences in rates of progression and concomitant comorbidities. Definitive diagnoses are crucial to guide management and treatment now and in the future. As targeted treatments emerge, it will be important for clinicians to understand the nomenclature, diagnosis, clinical manifestations, and treatments of the LGMDs.

Address correspondence to Dr Matthew P. Wicklund Department of Neurology, University of Colorado School of Medicine, Mail Stop B185, Academic Office 1, 12631 E 17th Ave, Room 5223, Aurora, CO 80045, [email protected].

RELATIONSHIP DISCLOSURE: Dr Wicklund has received personal compensation for serving on the scientific advisory boards of Myonexus Therapeutics, Inc and Sarepta Therapeutics. Dr Wicklund has served on the editorial board of Muscle & Nerve, has held stock or stock options for Myonexus Therapeutics, Inc, and has received research/grant support as principal investigator of studies for Acceleron Pharma, Inc; the Muscular Dystrophy Association; and Orphazyme.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Dr Wicklund discusses the unlabeled/investigational use of cell replacement therapies, gene editing, and viral vector gene therapy for the treatment of limb-girdle muscular dystrophies.

© 2019 American Academy of Neurology.