Myotilinopathy

Myotilinopathy (Orphanet code 209224) is a rare inherited muscle disorder caused by mutations in the MYOT gene, which encodes myotilin, a structural protein of the sarcomeric Z-disc in skeletal muscle. Myotilinopathy belongs to the group of myofibrillar myopathies (MFM), specifically classified as myofibrillar myopathy type 3 (MFM3). It is also known as MYOT-related myofibrillar myopathy. The disease primarily affects skeletal muscle, leading to progressive muscle weakness and wasting. Cardiac involvement, including cardiomyopathy and cardiac conduction defects, may also occur in some patients, and peripheral neuropathy has been reported. Clinical features typically include slowly progressive proximal and/or distal limb muscle weakness, often beginning in the lower extremities. Patients may experience difficulty walking, foot drop, and progressive gait impairment. Muscle biopsy characteristically shows myofibrillar disorganization with abnormal protein aggregates containing desmin, myotilin, and other Z-disc proteins. Serum creatine kinase levels may be normal or mildly elevated. Some patients develop respiratory insufficiency as the disease progresses. Onset is typically in adulthood, usually after the age of 40, though earlier presentations have been described. There is currently no cure or disease-specific treatment for myotilinopathy. Management is supportive and multidisciplinary, including physical therapy to maintain mobility, orthotic devices, respiratory support when needed, and cardiac monitoring for those with cardiac involvement. Genetic counseling is recommended for affected families. Research into potential therapies, including gene-based approaches, is ongoing but remains in early stages.

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