{"title":"Limb-Girdle Muscular Dystrophies.","authors":"Teerin Liewluck","doi":"10.1212/cont.0000000000001615","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This article reviews the current classification system, common subtypes, differential diagnosis, diagnostic algorithms, current management strategies, and evolving therapeutic areas for limb-girdle muscular dystrophies (LGMDs).</p><p><strong>Latest developments: </strong>There are currently five dominantly inherited LGMDs (LGMD-D1 to D5) and 29 recessively inherited LGMDs (LGMD-R1 to R29). Progress in molecular genetics makes next-generation sequencing gene panels the initial step in diagnosing LGMD and, in some cases, obviates the need for muscle biopsy. The panel should include LGMD genes and genes responsible for other hereditary myopathies and congenital myasthenic syndromes. Whole-exome sequencing or whole-genome sequencing can be performed before or after a muscle biopsy, depending on the specifics of each case. Once a diagnosis of LGMD is established, genetic counseling, symptomatic and supportive care, and cardiopulmonary surveillance remain the cornerstones of management. However, results from preclinical studies and early-stage clinical trials of genetic therapies for common LGMD-R subtypes are promising.</p><p><strong>Essential points: </strong>Progressive proximal weakness and hyperCKemia are hallmark features of LGMDs; however, they are not specific and can also be observed in many acquired and hereditary myopathies. Muscle biopsy is typically reserved for patients with negative or inconclusive genetic testing and can be particularly useful for verifying the pathogenicity of variants of uncertain significance. Advances in molecular genetics and genetic therapies have revolutionized the diagnostic landscape of LGMDs and paved the way for future disease-specific treatments.</p>","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"31 5","pages":"1344-1371"},"PeriodicalIF":0.0000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CONTINUUM Lifelong Learning in Neurology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1212/cont.0000000000001615","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/10/2 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: This article reviews the current classification system, common subtypes, differential diagnosis, diagnostic algorithms, current management strategies, and evolving therapeutic areas for limb-girdle muscular dystrophies (LGMDs).
Latest developments: There are currently five dominantly inherited LGMDs (LGMD-D1 to D5) and 29 recessively inherited LGMDs (LGMD-R1 to R29). Progress in molecular genetics makes next-generation sequencing gene panels the initial step in diagnosing LGMD and, in some cases, obviates the need for muscle biopsy. The panel should include LGMD genes and genes responsible for other hereditary myopathies and congenital myasthenic syndromes. Whole-exome sequencing or whole-genome sequencing can be performed before or after a muscle biopsy, depending on the specifics of each case. Once a diagnosis of LGMD is established, genetic counseling, symptomatic and supportive care, and cardiopulmonary surveillance remain the cornerstones of management. However, results from preclinical studies and early-stage clinical trials of genetic therapies for common LGMD-R subtypes are promising.
Essential points: Progressive proximal weakness and hyperCKemia are hallmark features of LGMDs; however, they are not specific and can also be observed in many acquired and hereditary myopathies. Muscle biopsy is typically reserved for patients with negative or inconclusive genetic testing and can be particularly useful for verifying the pathogenicity of variants of uncertain significance. Advances in molecular genetics and genetic therapies have revolutionized the diagnostic landscape of LGMDs and paved the way for future disease-specific treatments.
期刊介绍:
Continue your professional development on your own schedule with Continuum: Lifelong Learning in Neurology®, the American Academy of Neurology" self-study continuing medical education publication. Six times a year you"ll learn from neurology"s experts in a convenient format for home or office. Each issue includes diagnostic and treatment outlines, clinical case studies, a topic-relevant ethics case, detailed patient management problem, and a multiple-choice self-assessment examination.