Bethlem muscular dystrophy

Bethlem muscular dystrophy (also known as Bethlem myopathy or early-onset benign autosomal dominant limb-girdle myopathy with contractures) is a relatively mild form of collagen VI-related muscular dystrophy. It is caused by mutations in the COL6A1, COL6A2, or COL6A3 genes, which encode the three alpha chains of type VI collagen — a key structural protein found in the extracellular matrix of skeletal muscle and connective tissues. The disease primarily affects the skeletal muscular system, leading to progressive proximal muscle weakness and characteristic joint contractures, particularly of the fingers (long finger flexors), wrists, elbows, and ankles. Onset is variable but often occurs in early childhood, though some individuals may not be diagnosed until adulthood. Affected individuals typically present with mild to moderate proximal limb weakness, hypotonia in infancy, and slowly progressive contractures of multiple joints. A distinctive feature is the combination of distal joint hyperlaxity (especially in the fingers and wrists during childhood) with proximal joint contractures. Skin findings such as follicular hyperkeratosis (rough, bumpy skin on the arms and legs), keloid formation, and soft, velvety skin on the palms and soles may also be present. Most patients remain ambulatory into adulthood, though some may require assistive devices later in life. Respiratory function can decline slowly over decades, and a subset of patients may eventually require nocturnal ventilatory support. There is currently no cure or disease-specific treatment for Bethlem muscular dystrophy. Management is supportive and multidisciplinary, including physical therapy to maintain joint mobility and muscle strength, orthopedic interventions for contractures, and monitoring of respiratory function. Genetic counseling is recommended for affected families. Research into collagen VI biology and potential therapeutic strategies, including gene therapy approaches, is ongoing.

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