Congenital muscular dystrophy

Until several years ago, the congenital muscular dystrophies (CMD) were the Cinderellas of the neuromuscular disorders. There was no consensus on the existence of different forms, no knowledge of the pathogenesis, and frequent misdiagnosis. Recently, however, rapid advances in our understanding of various aspects of CMDs have occurred, and CMDs have gained their deserved place among the well-characterized muscular dystrophies. Recent developments in the CMD field are a remarkable example of an integrated clinical, biochemical, and molecular approach to the characterization of a disorder. The article by Pegoraro et al.1 in this issue of Neurology confirms the primary role of the LAMA2 gene that encodes the laminin α2 chain in one form of classic CMD; the article by Cohn et al.,2 also in this issue, emphasizes the broad clinical spectrum known to exist in CMD, and confirms the importance of examining secondary changes and the expression of several proteins within one sample. Clinical diversity in CMDs has been recognized for many years, and the severity and variable involvement of the eyes and brain differentiated Japanese cases described by Fukuyama and Finnish cases described by Santovouri (muscle eye brain disease) from the more classic cases in other geographic regions (see reference 3). Clarification of the various forms, however, did not emerge until the European Neuromuscular Center(ENMC) consortium was established. At the first workshop, four clinical categories were defined, and a collaborative strategy to identify the molecular basis of each was established.3 Exploration then advanced rapidly. Arahata's group reported reduced expression of the laminin α2 chain (then referred to as laminin M or merosin) in Fukuyama CMD (FCMD), and raised the possibility of a major role of the basal lamina in this condition.4 Shortly thereafter, the locus for FCMD was mapped to chromosome 9q, implying that the …