Congenital Myofibrillar Myopathy Type 1

Abstract

Myofibrillar myopathies (MFM) are a group of morphologically homogeneous but genetically heterogeneous muscle disorders. The pathologic findings in myofibrillar myopathy have been described in the past in various ways, including “inclusion bodies,” “intrasarcoplasmic dense granulofilamentous material,” “spheroid bodies,” “sarcoplasmic bodies,” “cytoplasmic bodies,” “Mallory body-like inclusions,” and “subsarcolemmal vermiform deposits.” The morphological changes in muscle result from disruption of the sarcomeric Z disc and the myofibrils, followed by accumulation of multiple proteins involved in the Z disc, including desmin, alpha-B-crystallin, myotilin, ZASP, filamin-C, and BAG3.

Desmin-related myopathy is characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias, and restrictive heart failure and by accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells, usually in addition to other sarcomeric proteins. In affected members of a family with autosomal dominant inheritance of a desmin-related cardioskeletal myopathy, Goldfarb et al. identified a heterozygous mutation in the desmin gene (Table 45.1). In three affected members of a second family with apparent autosomal recessive inheritance of a more severe disorder, two compound heterozygous mutations in the desmin gene were found. Arrhythmogenic right ventricular dysplasia 7 is another desmin-related myopathy.