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Limb-Girdle Dystrophy

By

Michael Rubin

, MDCM, Weill Cornell Medical College

Last full review/revision Jul 2020| Content last modified Jul 2020
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Limb-girdle dystrophy is a muscular dystrophy that has numerous subtypes; some are autosomal recessive and some are autosomal dominant. Time of onset is determined by the mode of inheritance, but the disease often begins in childhood. Symptoms are slowly progressive, impacting the proximal muscles. Diagnosis is by DNA analysis and muscle biopsy. Treatment is focused on maintenance of function and prevention of contractures.

Muscular dystrophies are inherited, progressive muscle disorders resulting from defects in one or more genes needed for normal muscle structure and function; dystrophic changes (eg, muscle fiber necrosis and regeneration) are seen on biopsy specimens.

Limb-girdle dystrophy at last count has 31 known subtypes, 23 autosomal recessive and 8 autosomal dominant. The overall incidence is estimated to be around 20 to 40/1,000,000. Males and females are affected equally.

Insights from molecular biology have redefined the way these disorders are classified. Autosomal dominant forms are classified as LGMD 1A, -1B, -1C, and so on, and recessive forms are classified as LGMD 2A, -2B, -2C, and so on. Several chromosomal loci have been identified for autosomal dominant (5q [no known gene product]) and recessive (2q, 4q [beta-sarcoglycan], 13q [gamma-sarcoglycan], 15q [calpain, a calcium-activated protease], and 17q [alpha-sarcoglycan or adhalin]) forms. Structural (eg, dystrophin-associated glycoproteins) or nonstructural (eg, proteases) proteins can be affected.

Symptoms and Signs

Patients typically present with slowly progressive, symmetric, proximal muscle weakness with or without facial involvement and diminished or absent tendon reflexes. The pelvic or shoulder girdle muscles can be affected first. Onset of symptoms for autosomal dominant types ranges from early childhood to adulthood. Onset of symptoms for autosomal recessive types tends to be during childhood, and these types primarily have a pelvic-girdle distribution.

Diagnosis

  • DNA mutation analysis

  • Sometimes muscle biopsy

Diagnosis of limb-girdle dystrophy is indicated by characteristic clinical findings, age at onset, and family history and requires mutation analysis of DNA from peripheral blood leukocytes as the primary confirmatory test. Muscle histology, immunocytochemistry, and Western blot analysis can be done.

Treatment

  • Maintenance of function and prevention of contractures

Treatment of limb-girdle dystrophy focuses on maintaining function and preventing contractures. Guidelines issued by the American Academy of Neurology recommend that newly diagnosed LGMD patients at high risk of cardiac complications be referred for cardiac evaluation, even in the absence of cardiac symptoms. Those at high risk of respiratory failure should undergo pulmonary function testing. All LGMD patients should ideally be referred to a multi-specialty clinic with expertise in neuromuscular disorders.

There is currently no role for gene therapy, myoblast transplantation, neutralizing antibody to myostatin, or growth hormone other than in a research study (1).

Treatment reference

  • 1. Narayanaswami P, Weiss M, Selcen D, et al: Evidence-based guideline summary: Diagnosis and treatment of limb-girdle and distal dystrophies: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. Neurology 83:1453–1463, 2014. doi: 10.1212/WNL.0000000000000892.

More Information

The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

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NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version
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