Genetic skeletal muscle disease

Genetic skeletal muscle disease (Orphanet code 206634) is a broad category encompassing a large and heterogeneous group of inherited disorders that primarily affect skeletal muscle structure and/or function. These conditions are caused by mutations in genes encoding proteins essential for muscle fiber integrity, contraction, metabolism, or signaling. The skeletal muscles throughout the body are the primary system affected, leading to symptoms such as progressive muscle weakness, muscle wasting (atrophy), exercise intolerance, muscle pain (myalgia), and in some cases muscle stiffness or cramps. Depending on the specific subtype, respiratory muscles and cardiac muscle may also be involved, potentially leading to breathing difficulties and cardiomyopathy. This grouping includes numerous distinct entities such as muscular dystrophies (e.g., Duchenne, Becker, limb-girdle types), congenital myopathies (e.g., nemaline myopathy, central core disease), metabolic myopathies (e.g., glycogen storage diseases affecting muscle), and myotonic disorders, among others. Age of onset, severity, and progression vary widely depending on the specific genetic defect. Some forms present at birth or in infancy with severe hypotonia and feeding difficulties, while others may not manifest until adulthood with slowly progressive limb-girdle weakness. Treatment for genetic skeletal muscle diseases is largely supportive and depends on the specific diagnosis. Management may include physical therapy, respiratory support, cardiac monitoring, orthopedic interventions, and nutritional support. Gene-specific therapies are emerging for certain subtypes, such as antisense oligonucleotide treatments for Duchenne muscular dystrophy and enzyme replacement therapy for Pompe disease. Genetic counseling is essential for affected families. Diagnosis typically involves clinical evaluation, serum creatine kinase measurement, electromyography, muscle biopsy, and increasingly, molecular genetic testing including next-generation sequencing panels.

Common questions about Genetic skeletal muscle disease