Harper_2004_Semin.Neurol_24_111

Congenital myasthenic syndromes are genetic disorders of neuromuscular transmission that should be considered in the differential diagnosis of seronegative myasthenia gravis and other neuromuscular disorders. They are present at birth but may not manifest until childhood or adult life. A classification system of congenital myasthenic syndromes based on molecular genetics is under evolution. Clinical and neurophysiological correlations with molecular studies have defined diagnostic criteria that assist the clinician in identifying specific clinical myasthenic syndromes. Some types of congenital myasthenia (e.g., slow-channel and fast-channel syndrome, acetylcholinesterase deficiency, and choline acetyltransferase deficiency) can be identified by clinical features, response to cholinesterase inhibitors, and standard electrodiagnostic studies. The molecular genetics, pathogenesis, clinical features, differential diagnosis, natural history, and treatment of well-characterized congenital myasthenic syndromes are discussed.