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Review
. 2025 Nov 25;105(10):e214291.
doi: 10.1212/WNL.0000000000214291. Epub 2025 Oct 28.

Expert Consensus on Genetic Diagnostic Approaches for Patients With Limb-Girdle Muscular Dystrophy

Volker Straub  1 , Amanda R Clause  2 , Sandra Donkervoort  3 , Peter B Kang  4   5 , Chamindra G Laverty  6 , Zhiyv Niu  7 , Matthew P Wicklund  8 , Carsten G Bönnemann  3 , Sandra T Cooper  9   10   11 , Jordi Díaz-Manera  1 , Nicholas E Johnson  12 , Pushpa Narayanaswami  13 , John Vissing  14 , Maggie C Walter  15 , Caryne Craige  16 , Conrad C Weihl  2
Affiliations
Review

Expert Consensus on Genetic Diagnostic Approaches for Patients With Limb-Girdle Muscular Dystrophy

Volker Straub et al. Neurology. .

Abstract

Limb-girdle muscular dystrophy (LGMD) is the phenotypic description of a clinically and genetically diverse group of inherited neuromuscular disorders involving proximal muscles of the pelvic and shoulder girdles. There are currently over 30 different genetic forms of LGMD, and despite diagnostic advances, accurate diagnoses may be difficult to achieve. Although clinical diagnosis of a patient with a specific form of LGMD is possible in some cases, a precise and timely genetic diagnosis can be crucial to anticipate and prevent complications associated with particular genetic forms of LGMD (e.g., extramuscular manifestations such as cardiac, respiratory, or cognitive impairments). With the rapid pace of genetic testing advances, updates on training and education are imperative to support the correct use of these tests. We formed an expert consensus to provide an efficient diagnostic approach meant to empower clinicians in the use of genetic and other supportive tests. Informed selection and interpretation of a gene panel; use of genome or exome sequencing; and use of biochemical, imaging, pathology, and electromyography tests are discussed here. Ultimately, genetic testing should help to confirm a diagnosis and guide treatment decisions or counseling services.

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Conflict of interest statement

V. Straub received speaker honoraria from Italfarmaco, Pfizer, Roche, and Sarepta Therapeutics, and consultancy fees for scientific advice and meeting contributions from Astellas Gene Therapies, Bayer, Biogen, Edgewise Therapeutics, Entrada Therapeutics, ML Bio Solutions, Roche, Sanofi Genzyme, and Sarepta Therapeutics; receives research funding from Sanofi Genzyme and Sarepta Therapeutics, and is supported by the National Institute for Health and Care Research Newcastle Biomedical Research Centre as part of his employment with Newcastle University and Newcastle Hospitals NHS Foundation Trust. A.R. Clause and S. Donkervoort report no disclosures relevant to the manuscript. P.B. Kang has received personal compensation for serving as a consultant for Neurogene, for serving on advisory boards for Lupin and ITF Therapeutics (Italfarmaco), and for serving as an associate editor for Wiley and as an editor for the American Academy of Neurology; he has received research support from ML Bio Solutions and Sarepta Therapeutics and publishing royalties for authoring content for UpToDate (Wolters Kluwer); and has been a medical advisory board member with the Speak Foundation, President of the Child Neurology Society, and an ex officio Board Member with the Child Neurology Foundation, all without compensation. The institution of P.B. Kang has received research support from Sarepta Therapeutics, Xtraordinary Joy Foundation, Centers for Disease Control and Prevention (CDC), NIH, National Initiative for Cockayne Syndrome, the Greg Marzolf Jr. Foundation, Edgewise, and ML Bio. The institution of an immediate family member of P.B. Kang has received research support from Sarepta Therapeutics, the NIH, and the US Food and Drug Administration (FDA), and an immediate family member of P.B. Kang has received intellectual property interests from a discovery or technology relating to health care. C.G. Laverty reports compensation as a consultant on advisory boards for Sarepta Therapeutics, Novartis, Biogen, Dyne, the Muscular Dystrophy Association, Solid Biosciences, and UCB. Z. Niu reports consultation for Genome Medical Inc. and Sarepta and honoraria from AANEM, for which activities are approved by Mayo Clinic. M.P. Wicklund has acted as a paid consultant on advisory boards for Amicus Therapeutics, Edgewise Therapeutics, Jazz Pharmaceuticals, Juvena Therapeutics, ML Bio Solutions, Sarepta Therapeutics, and UCB; and he receives research support from Catalyst Pharmaceuticals, Fulcrum Therapeutics, and Sarepta Therapeutics. C.G. Bönnemann reports no disclosures relevant to the manuscript. S.T. Cooper has received support from an Australian NHMRC Grant Level L3 (APP2017952, 2023–2027); she has no existing financial relationships that will benefit from publication of these data; she is the named inventor of intellectual property (IP) relating to splicing variant detection (PCT/AU2019/000141; PCT/AU2020/050234) owned jointly by The University of Sydney and Sydney Children's Hospitals Network and is the Director of Frontier Genomics, which has licensed this IP; she currently receives no consultancy fees or other remuneration for her Directorship role. J. Díaz-Manera received speaker honoraria from Amicus, Sanofi, Lupin, and Sarepta Therapeutics and consultancy fees for scientific advice and meeting contributions from Astellas Gene Therapies, Biogen, Entrada Therapeutics, ML Bio Solutions, Roche, Sanofi Genzyme, and Sarepta Therapeutics; receives research funding from Sanofi Genzyme, Amicus, Spark, Astellas, Sarepta Therapeutics, and Italfarmaco; and is supported by the National Institute for Health and Care Research Newcastle Biomedical Research Centre as part of his employment with Newcastle University and Newcastle Hospitals NHS Foundation Trust. N.E. Johnson is a cofounder of Repeat RNA Therapeutics Inc., and Myogene therapies; has received grant funding from National Institute of Neurological Disorders and Stroke (R01NS104010, U01NS124974), NCATS (R21TR003184), the CDC (U01DD001242), and the FDA (7R01FD006071); receives royalties from the Congenital and Childhood Myotonic Dystrophy Health Index (CCMDHI) and the Charcot-Marie-Tooth Health Index (CMTHI); and receives research funds from Novartis, Takeda, PepGen, Sanofi Genzyme, Dyne, Vertex Pharmaceuticals, Fulcrum Therapeutics, AskBio, ML Bio, and Sarepta; and has provided consultation for Arthex, Angle Therapeutics, Juvena, Rgenta, PepGen, AMO Pharma, Takeda, Design, Dyne, AskBio, Avidity, and Vertex Pharmaceuticals. P. Narayanaswami has received research support from the NIH, Alexion, and the Patient-Centered Outcomes Research Institute (PCORI); consultations/advisory boards include Alexion, Amgen, Argenx, Cabaletta-Bio, CVS, Dianthus, GlaxoSmithKline, Immune Abs, Immunovant, Johnson & Johnson, Merck, Novartis, UCB, and Viridian; data monitoring boards include Sanofi, Argenx, and NMD Pharma; and royalties are from Springer Nature. J. Vissing has acted as a paid consultant on advisory boards for Roche, Sanofi Genzyme, Sarepta Therapeutics, Fulcrum Therapeutics, Biogen, Amicus, Regeneron, argenx BVBA, UCB Biopharma SPRL, Arvinas, ML Biopharma, Edgewise Therapeutics, Atamyo, Amgen, Dyne Therapeutics, Janssen Pharmaceuticals, Benitic Biopharma, Novartis, Lupin Atlantis Holdings SA, Johnson & Johnson, Solid Biosciences, Entrada Therapeutics, Avidity Biosciences, and Italfarmaco; and has received research, travel support, and/or speaker honoraria from Sanofi Genzyme, Alexion Pharmaceuticals, Edgewise Therapeutics, Fulcrum Therapeutics, UCB Biopharma SPRL, Amgen, and Johnson & Johnson. M.C. Walter has served on advisory boards for AveXis, Biogen, Novartis, Pfizer, Roche, Santhera, Sarepta, Pharnext, PTC Therapeutics, Ultragenyx, and Wave Sciences; received funding for travel or speaker honoraria from AveXis, Biogen, PTC Therapeutics, Ultragenyx, Santhera, and Sarepta; and worked as an ad hoc consultant for AskBio, Audentes Therapeutics, AveXis, Biogen Pharma GmbH, Fulcrum Therapeutics, GLG Consult, Guidepoint Global, Gruenenthal Pharma, Novartis, Pharnext, PTC Therapeutics, and Roche. C. Craige is a contractor with Symbiotix, part of Havas Health & You, which provided funding for the manuscript. C.C. Weihl has received consultant fees for advising ML Bio Solutions and Sarepta Therapeutics. Go to Neurology.org/N for full disclosures.

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