Journal of Neurology

, Volume 261, Issue 11, pp 2234–2243 | Cite as

Inherited disorders of the neuromuscular junction: an update

  • Pedro M. Rodríguez Cruz
  • Jacqueline Palace
  • David BeesonEmail author
Neurological Update


Congenital myasthenic syndromes (CMSs) are a group of heterogeneous inherited disorders caused by mutations in genes affecting the function and structure of the neuromuscular junction. This review updates the reader on established and novel subtypes of congenital myasthenia, and the treatment strategies for these increasingly heterogeneous disorders. The discovery of mutations associated with the N-glycosylation pathway and in the family of serine peptidases has shown that causative genes encoding ubiquitously expressed molecules can produce defects at the human neuromuscular junction. By contrast, mutations in lipoprotein-like receptor 4 (LRP4), a long-time candidate gene for congenital myasthenia, and a novel phenotype of myasthenia with distal weakness and atrophy due to mutations in AGRN have now been described. In addition, a pathogenic splicing mutation in a nonfunctional exon of CHRNA1 has been reported emphasizing the importance of analysing nonfunctional exons in genetic analysis. The benefit of salbutamol and ephedrine alone or combined with pyridostigmine or 3,4-DAP is increasingly being reported for particular subtypes of CMS.


Congenital myasthenia Congenital myasthenic syndromes Neuromuscular junction N-glycosylation pathway Salbutamol Ephedrine Prolyl-endopeptidase-like gene (PREPL) deficiency Congenital myopathies Agrin 



We gratefully acknowledge the UK National Specialised Commissioning Team for funding to the Diagnostic and Advisory service for CMS in Oxford.

Conflicts of interest



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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Pedro M. Rodríguez Cruz
    • 1
  • Jacqueline Palace
    • 1
  • David Beeson
    • 1
    • 2
    Email author
  1. 1.Nuffield Department of Clinical NeurosciencesUniversity of OxfordOxfordUK
  2. 2.Neurosciences Group, Weatherall Institute of Molecular MedicineUniversity of Oxford, The John Radcliffe HospitalOxfordUK

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