Congenital disorders of neuromuscular transmission

Congenital neuromuscular transmission defects are uncommon but challenging diseases for the clinical neurologist. Some of these disorders entail severe or even life-threatening disability; some are treatable, but effective therapy requires precise diagnosis, and the precise diagnosis is often difficult to make. The diagnosis rests on the combination of clinical data, the electromyogram (EMG), and additional studies that may include microelectrode analysis of neuromuscular transmission, ultrastructural and cytochemical studies of the neuromuscular junction (NMJ), and biochemical studies on muscle specimens. Understandably, these studies often depend on the collaboration of several investigators. In each congenital myasthenic disorder, a genetically determined primary abnormality affects neuromuscular transmission directly or causes secondary derangements that eventually affect transmission. In either case, the safety margin of neuromuscular transmission is eventually compromised by one or more specific mechanisms. Therefore a clear grasp of the factors that affect the safety margin is essential for understanding these disorders.