Miyoshi myopathy

Miyoshi myopathy (also known as Miyoshi distal myopathy or distal myopathy with anterior tibial onset type 1) is a rare inherited muscular dystrophy that primarily affects the distal muscles of the legs, particularly the posterior compartment (calf muscles). It belongs to the group of dysferlinopathies, caused by mutations in the DYSF gene located on chromosome 2p13, which encodes the protein dysferlin. Dysferlin plays a critical role in muscle membrane repair, and its deficiency leads to progressive muscle fiber degeneration. Miyoshi myopathy is allelic with limb-girdle muscular dystrophy type R2 (LGMDR2), meaning both conditions arise from mutations in the same gene but present with different patterns of muscle involvement. The disease typically presents in late adolescence or early adulthood (usually between ages 15 and 30), with progressive weakness and atrophy of the calf muscles (gastrocnemius and soleus). Affected individuals often notice difficulty standing on tiptoes, climbing stairs, or walking on uneven surfaces. A hallmark feature is markedly elevated serum creatine kinase (CK) levels, often 10 to 100 times the normal range, reflecting ongoing muscle damage. Over time, the weakness may spread to involve proximal muscles of the legs and arms, and some patients may eventually require wheelchair assistance, typically years to decades after onset. Muscle MRI characteristically shows fatty replacement of the posterior calf compartment muscles early in the disease course. There is currently no cure or disease-modifying treatment for Miyoshi myopathy. Management is supportive and multidisciplinary, including physical therapy to maintain mobility and prevent contractures, occupational therapy, orthotic devices, and monitoring for cardiac and respiratory complications (though these are uncommon). Genetic counseling is recommended for affected families. Research into gene therapy, dysferlin replacement strategies, and other molecular approaches is ongoing, offering hope for future therapeutic options.

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