Limb-girdle and distal dystrophies

Limb-girdle and distal dystrophies are rare genetic neuromuscular disorders characterized by progressive muscle weakness and atrophy.

The pathophysiology of these disorders involves genetic mutations that lead to the dysfunction of key proteins in muscle cells. In limb-girdle muscular dystrophies, the genetic defects responsible for over 30 subtypes have been identified, with the causative mutations mostly found in limb-girdle muscular dystrophy-associated genes.

The prevalence of limb-girdle and distal dystrophies in the United Kingdom is estimated at 0.18 per 100,000 population.

Clinically, limb-girdle and distal dystrophies usually manifest in the proximal muscles of the hip and shoulder girdles. The disease progression is typically characterized by progressive muscular dystrophy, which can be exacerbated by exercise. Distal muscular dystrophy, on the other hand, is characterized by weakness and atrophy in the distal muscles, such as those in the hands and feet. The clinical presentation of distal muscular dystrophy can vary, but it often includes juvenile or early adult onset of muscle weakness.

The prognosis of these disorders is generally poor due to their progressive nature. While no curative therapies exist, the clinical severity can vary, with the order of decreasing clinical severity being: sarcoglycanopathy, calpainopathy, dysferlinopathy, and caveolinopathy.