Limb-Girdle Muscular Dystrophy

Limb-Girdle Muscular Dystrophies are classified into autosomal dominant (LGMD1) and autosomal recessive (LGMD2/R) forms, further subdivided by specific genetic mutations. Genetic subtypes affect proteins involved in various cellular functions: sarcolemmal proteins (dystroglycans, sarcoglycans, caveolin), contractile proteins (titin, nebulin), Z-disk proteins, and ubiquitin proteasome pathway components. These proteins are critical for maintaining the structural integrity of muscle and proper cellular signaling. Mutations lead to muscle fiber degeneration, inflammation, and progressive replacement by fat and fibrotic tissue. Different genetic subtypes correlate with different clinical presentations, progression rates, and systemic manifestations. LGMD typically manifests with proximal weakness, affecting hip and shoulder muscles. Patients experience difficulty climbing stairs, rising from chairs, and overhead activities. Gait becomes increasingly waddling and wide-based as disease progresses. Some LGMD subtypes include cardiomyopathy (LGMD1B, LGMD2I, LGMD2L, LGMD2K), requiring cardiac monitoring. Respiratory involvement may develop in advanced disease. Disease progression rates vary significantly among subtypes, from indolent forms with slow progression to rapidly progressive forms leading to wheelchair dependence within years of onset.