Myofibrillar myopathy

Myofibrillar myopathy (MFM) is a group of rare inherited neuromuscular disorders characterized by the progressive disintegration of myofibrils (the contractile units of muscle fibers) and abnormal accumulation of degraded muscle proteins within muscle cells. The disease primarily affects skeletal muscle, leading to progressive muscle weakness that typically begins in the distal limbs (hands and feet) and may spread to involve proximal muscles. Cardiac involvement is common and can manifest as cardiomyopathy (dilated or hypertrophic) and cardiac conduction defects, which may be life-threatening. Peripheral neuropathy and respiratory insufficiency are also frequently observed. MFM is also known as desmin-related myopathy or protein aggregate myopathy, depending on the specific genetic subtype. Several genes have been implicated in myofibrillar myopathy, including DES (desmin), CRYAB (alpha-B crystallin), MYOT (myotilin), ZASP/LDB3, FLNC (filamin C), BAG3, FHL1, and TTN (titin), among others. These genes encode proteins critical for the structural integrity of the sarcomere and cytoskeleton. Muscle biopsy typically reveals characteristic findings including amorphous or granular deposits, rimmed vacuoles, and accumulation of multiple proteins such as desmin, alpha-B crystallin, and dystrophin. Diagnosis is confirmed through a combination of clinical evaluation, muscle biopsy with immunohistochemistry, and genetic testing. There is currently no cure or disease-specific treatment for myofibrillar myopathy. Management is supportive and multidisciplinary, focusing on physical therapy to maintain mobility, cardiac monitoring and treatment of arrhythmias or heart failure (including pacemaker or implantable defibrillator placement when indicated), respiratory support for ventilatory insufficiency, and orthopedic interventions as needed. Prognosis varies depending on the genetic subtype and the degree of cardiac and respiratory involvement. Genetic counseling is recommended for affected individuals and their families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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