Congenital Myofibrillar Myopathy Type 6

Abstract

Myofibrillar myopathies (MFM) are a group of morphologically homogeneous but genetically heterogeneous chronic muscle disorders. The morphological changes in muscle result from disruption of the sarcomeric Z disc and myofibrils, with abnormal accumulation of multiple proteins of the Z disc, including desmin, alpha-B-crystallin, myotilin, ZASP, filamin-C, and BAG3 (Table 35.1). The disease is characterized by progressive limb and axial muscle weakness associated with cardiomyopathy and severe respiratory insufficiency during adolescence. To date, three unrelated cases have been described with childhood onset of rapidly progressive myofibrillar myopathy in which the same heterozygous mutation in the BAG3 gene was found. Two patients presented with a rigid spine and one a peripheral neuropathy. Disintegration of Z discs, extensive accumulation of granular debris and larger inclusions, and apoptosis of a small fraction of the nuclei characterize the disease. Members of the BAG family, including BAG3, are cytoprotective proteins that bind to and regulate Hsp70 family molecular chaperones.