Overview of distal myopathies: from the clinical to the molecular

Abstract

Five distinct predominantly distal myopathies have been identified with discrete clinical and genetic patterns as follows: (1) Welander myopathy (late adult onset, type 1), with autosomal dominant inheritance and unknown molecular localization; (2) Markesbery-Griggs/Udd myopathies (late adult onset, type 2), with autosomal dominant inheritance and linkage to chromosome 2q; (3) Nonaka myopathy (early adult onset, type 1), with autosomal recessive inheritance and molecular localization to 9p1-q1. Nonaka myopathy is identical to quadriceps-sparing familial inclusion body myopathy; (4) Miyoshi myopathy (early adult onset, type 2), with autosomal recessive inheritance and localization to 2p; (5) Laing myopathy (early onset, type 3), with autosomal dominant inheritance and linkage to chromosome 14. The gene and abnormal gene product have not yet been defined for any of the distal myopathies. However, it is already clear that disorders allelic to the distal myopathies can begin with proximal weakness. Given such major phenotypic variation, it is possible that some of the diseases we regard as distal myopathies may become obsolete. Instead, these conditions may become known by their genetic mutation or abnormal gene product, much like Duchenne and Becker dystrophy.