title: Congenital myasthenic syndromes.
abstract: OBJECTIVE
  Congenital myasthenic syndromes are a heterogeneous group of diseases caused by genetic defects affecting neuromuscular transmission. In this article, a strategy that leads to the diagnosis of congenital myasthenic syndromes is presented, and recent advances in the clinical, genetic and molecular aspects of congenital myasthenic syndrome are outlined.
  
  
  RESULTS
  Besides the identification of new mutations in genes already known to be implicated in congenital myasthenic syndromes (genes for the acetylcholine receptor subunits and the collagen tail of acetylcholinesterase), mutations in other genes have more recently been discovered and characterized (genes for choline acetyltransferase, rapsyn, and the muscle sodium channel SCN4A). Fluoxetine has recently been proposed as an alternative treatment for 'slow channel' congenital myasthenic syndrome.
  
  
  CONCLUSIONS
  The characterization of congenital myasthenic syndromes comprises two complementary steps: establishing the diagnosis and identifying the pathophysiological type of congenital myasthenic syndrome. Characterization of the type of congenital myasthenic syndrome has allowed it to be classified as caused by presynaptic, synaptic and postsynaptic defects. A clinically and muscle histopathologically oriented genetic study has identified several genes in which mutations cause the disease. Despite comprehensive characterization, the phenotypic expression of one given gene involved is variable, and the aetiology of many congenital myasthenic syndromes remains to be discovered.
authors.affiliation: Inserm U582 and Unité Clinique de Pathologie Neuromusculaire, Institut de Myologie, Hôpital de la Salpêtrière, Paris, France. d.hantai@myologie.chups.jussieu.fr
authors.forename: Daniel
authors.initials: D
authors.lastname: Hantaï
authors.forename: Pascale
authors.initials: P
authors.lastname: Richard
authors.forename: Jeanine
authors.initials: J
authors.lastname: Koenig
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
mesh_terms: D000110:Acetylcholinesterase / Q000172:deficiency; D000818:Animals; D005838:Genotype; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D020294:Myasthenic Syndromes, Congenital / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000502:physiology; D010641:Phenotype; D011379:Prognosis
chemical_list: D009124:Muscle Proteins; C051609:peripheral membrane protein 43K; D000110:Acetylcholinesterase