[Myofibrillar myopathy]

Myofibrillar myopathy (MFM) describes a group of hereditary myopathies pathologically characterized as markedly disorganized myofibrils with cytoplasmic inclusions. Seven disease-related genes have been identified, including DES, CRYAB, MYOT, ZASP, FLNC, BAG3, and FHL1, all of which encode proteins closely related to Z-line. MFM often occurs via autosomal dominant inheritance, but autosomal recessive, or X-linked, forms are also seen. The majority of Japanese patients have no family history. Clinical symptoms of MFM are quite variable. The age at onset ranges from infancy to the eighth decade of life. Some patients show limb girdle muscle involvement, whereas others show distal myopathy. Patients who have cardiomyopathy with no obvious muscle weakness are also seen. Skeletal muscles from MFM patients contain cytoplasmic inclusions called cytoplasmic or spheroid bodies. Immunohistochemically, cytoplasmic accumulations of various proteins are commonly seen, including Z-line proteins such as desmin, αB-crystallin, and myotilin; membrane proteins such as dystrophin and sarcoglycans; heat shock proteins; and ubiquitin. We review the clinical, pathological, and genetic characteristics of MFM patients, including those from our recent study results. Despite intensive mutation screening, about 70% of MFM patients in our series had no mutation in the known causative genes. The identification of novel disease-related genes and the development of efficient diagnostic tools are urgently needed, as is the elucidation of the pathomechanism of myofibril disorganization as a possible target for new treatments.