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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.
Prognosis and risk of recurrence
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.
The following summarized guidelines for the evaluation and management of limb-girdle and distal dystrophies are prepared by our editorial team based on guidelines from the American Heart Association (AHA/HRS/ACC 2019) and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM 2014).
Clinical assessment: use a clinical approach to guide genetic diagnosis based on clinical phenotype, inheritance pattern, and associated manifestations.
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Pulmonary function testing
Gene therapy: avoid offering gene therapy, myoblast transplantation, neutralizing antibodies to myostatin, or GH for patients with limb-girdle muscular dystrophy outside of a research study.
Permanent cardiac pacing: as per ACC 2019 guidelines, consider permanent pacing with additional defibrillator capability if needed and meaningful survival of > 1 year is expected in patients with Limb-girdle muscular dystrophy with a PR interval > 240 milliseconds and LBBB.
4.Follow-up and surveillance
Indications for specialist referral: refer newly diagnosed patients with limb-girdle muscular dystrophy subtype at high risk of cardiac complications for cardiology evaluation, even if they are asymptomatic from a cardiac standpoint.