ABSTRACT
Congenital myasthenic syndromes (CMSs) are inherited disorders of neuromuscular transmission that do not involve immunologic mechanisms. The mutations that produce CMSs alter the expression and function of ion channels, receptors, enzymes, or other accessory molecules that are needed to maintain the safety margin of neuromuscular transmission. In addition to a neuromuscular transmission defect, some CMSs are associated with secondary degenerative changes of muscle (i.e., endplate myopathy). Most CMSs are autosomal recessive disorders although at least one subtype, the slowchannel syndrome (SCCMS), is typically autosomal dominant. Ultrastructural, physiologic, and molecular genetic techniques have been used to define and classify the various CMSs (Table 6.1) and to design treatment strategies. Although these highly specialized studies are often necessary to make a specific diagnosis, correlation of these data with clinical manifestations and findings on electrodiagnostic studies, as well as increasing availability of genetic probes for specific mutations, has made it possible to diagnose and accurately classify many patients with CMS without the need for intercostal or anconeus muscle biopsy.
