Muscular dystrophies

Muscular dystrophies are characterised by progressive skeletal muscle weakness and wasting, with disease onset ranging from early childhood to late adulthood. Clinical presentation varies considerably between disease entities. Patterns of muscle involvement range from predominantly proximal limb-girdle weakness in the limb-girdle muscular dystrophies and dystrophinopathies to facial and scapular weakness in facioscapulohumeral muscular dystrophy, while other entities may present with distal or oculopharyngeal muscle involvement. Cardiac involvement and respiratory muscle weakness contribute substantially to morbidity in the more severe entities.

Prevalence estimates vary depending on the population studied. In a United Kingdom primary-care cohort, the prevalence of muscular dystrophies was estimated at 29.5/100,000 individuals.

Many genes have been associated with muscular dystrophies, reflecting the considerable genetic and clinical heterogeneity of these disorders. Muscular dystrophies encompass several groups, including myotonic dystrophies, dystrophinopathies, limb-girdle muscular dystrophies, and other less common phenotypes. Common forms include , a multisystem disorder caused by a CTG repeat expansion in the DMPK gene, and , a severe childhood-onset disorder caused by pathogenic variants in the DMD gene and characterized by progressive muscle weakness and loss of ambulation.

The inheritance patterns associated with muscular dystrophies include autosomal dominant, autosomal recessive, and X-linked inheritance.

• Where muscular dystrophies are suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

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