Congenital myasthenic syndromes

Congenital myasthenic syndromes (CMSs) are heterogeneous disorders. Clinical, electrophysiologic, and morphologic studies have paved the way for detecting CMS-related mutations in proteins residing in the nerve terminal, the synaptic basal lamina, and in the postsynaptic region of the motor endplate (EP). The disease proteins identified to date reside in the nerve terminal, the synaptic space, the postsynaptic region or occur in proteins subserving EP development and maintenance, or in proteins that subserve protein glycosylation. Myasthenic syndromes can also occur in combination with centronuclear myopathies and defects in plectin. Analysis of the properties of the expressed mutants has contributed to finding improved therapy for most CMS. Despite these advances, the molecular basis of some phenotypically characterized CMS awaits discovery.