Genetic basis and phenotypic features of congenital myasthenic syndromes

Research output: Chapter in Book/Report/Conference proceedingChapter

24 Scopus citations


The congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. The disease proteins reside in the nerve terminal, the synaptic basal lamina, or in the postsynaptic region, or at multiple sites at the neuromuscular junction as well as in other tissues. Targeted mutation analysis by Sanger or exome sequencing has been facilitated by characteristic phenotypic features of some CMS. No fewer than 20 disease genes have been recognized to date. In one-half of the currently identified probands, the disease stems from mutations in genes encoding subunits of the muscle form of the acetylcholine receptor (CHRNA1, CHRNB, CHRNAD1, and CHRNE). In 10–14% of the probands the disease is caused by mutations in RAPSN, DOK 7, or COLQ, and in 5% by mutations in CHAT. Other less frequently identified disease genes include LAMB2, AGRN, LRP4, MUSK, GFPT1, DPAGT1, ALG2, and ALG 14 as well as SCN4A, PREPL, PLEC1, DNM2, and MTM1. Identification of the genetic basis of each CMS is important not only for genetic counseling and disease prevention but also for therapy, because therapeutic agents that benefit one type of CMS can be harmful in another.

Original languageEnglish (US)
Title of host publicationNeurogenetics, Part II
EditorsDaniel H. Geschwind, Henry L. Paulson, Christine Klein
PublisherElsevier B.V.
Number of pages25
ISBN (Print)9780444640765
StatePublished - Jan 1 2018

Publication series

NameHandbook of Clinical Neurology
ISSN (Print)0072-9752
ISSN (Electronic)2212-4152


  • EMG
  • congenital myasthenic syndromes
  • exome sequencing
  • mutation analysis
  • neuromuscular junction
  • neuromuscular transmission
  • phenotypic clues
  • therapy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)


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