title: Congenital myasthenic syndromes and the neuromuscular junction.
abstract: OBJECTIVE
  Congenital myasthenic syndromes (CMS) are a group of heterogeneous inherited disorders caused by mutations in genes encoding proteins essential for the integrity of neuromuscular transmission. This review updates the reader on the new mutations of known CMS genes, new causative genes and the treatment strategies for these increasingly heterogeneous disorders. It also provides a brief summary of the congenital myopathies with myasthenic features.
  
  
  RESULTS
  The discovery of causative genes encoding for ubiquitously expressed and extrajunctional molecules has changed our previous view of congenital myasthenia. Mutations associated with the N-glycosylation pathway and in the family of serine peptidases have shown that abnormalities in the post-translational modification of proteins can produce defects at the human neuromuscular junction. However, mutations in lipoprotein-like receptor 4, a long-time candidate gene for congenital myasthenia, have now been described and a new pathogenic splicing mutation in the nonfunctional exon of CHRNA1 has been reported. The use of salbutamol and ephedrine alone or combined with pyridostigmine or 3,4-DAP is increasingly being reported in different CMS subtypes with significant benefit.
  
  
  CONCLUSIONS
  Recent studies of the CMS illustrate the increasing complexity of the genetics, pathophysiological mechanisms and therapy of impaired synaptic transmission at the neuromuscular junction.
authors.affiliation: aNuffield Department of Clinical Neurosciences, University of Oxford bNeurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Oxford, UK.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Rodríguez Cruz
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Palace
authors.forename: David
authors.initials: D
authors.lastname: Beeson
mesh_terms: D000818:Animals; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics / Q000473:pathology / Q000628:therapy; D009469:Neuromuscular Junction / Q000235:genetics / Q000503:physiopathology*; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000235:genetics
chemical_list: C523021:CHRNA1 protein, human; D026502:LDL-Receptor Related Proteins; C551781:LRP4 protein, human; D011978:Receptors, Nicotinic