How to Spot Congenital Myasthenic Syndromes Resembling the Lambert-Eaton Myasthenic Syndrome? A Brief Review of Clinical, Electrophysiological, and Genetics Features

Neuromolecular Med. 2018 Jun;20(2):205-214. doi: 10.1007/s12017-018-8490-1. Epub 2018 Apr 25.

Abstract

Congenital myasthenic syndromes (CMS) are heterogeneous genetic diseases in which neuromuscular transmission is compromised. CMS resembling the Lambert-Eaton myasthenic syndrome (CMS-LEMS) are emerging as a rare group of distinct presynaptic CMS that share the same electrophysiological features. They have low compound muscular action potential amplitude that increment after brief exercise (facilitation) or high-frequency repetitive nerve stimulation. Although clinical signs similar to LEMS can be present, the main hallmark is the electrophysiological findings, which are identical to autoimmune LEMS. CMS-LEMS occurs due to deficits in acetylcholine vesicle release caused by dysfunction of different components in its pathway. To date, the genes that have been associated with CMS-LEMS are AGRN, SYT2, MUNC13-1, VAMP1, and LAMA5. Clinicians should keep in mind these newest subtypes of CMS-LEMS to achieve the correct diagnosis and therapy. We believe that CMS-LEMS must be included as an important diagnostic clue to genetic investigation in the diagnostic algorithms to CMS. We briefly review the main features of CMS-LEMS.

Keywords: Congenital myasthenic syndromes; Lambert–Eaton myasthenic syndrome.

Publication types

  • Review

MeSH terms

  • Acetylcholine / physiology
  • Agrin / genetics
  • Autoimmunity
  • Calcium Signaling
  • Electrophysiology
  • Exercise
  • Exocytosis
  • Humans
  • Lambert-Eaton Myasthenic Syndrome / diagnosis*
  • Laminin / genetics
  • Myasthenic Syndromes, Congenital / diagnosis*
  • Myasthenic Syndromes, Congenital / genetics
  • Nerve Tissue Proteins / genetics
  • Neural Conduction
  • Neuromuscular Junction / physiopathology
  • SNARE Proteins / physiology
  • Synaptic Transmission
  • Synaptotagmin II / genetics
  • Vesicle-Associated Membrane Protein 1 / genetics

Substances

  • Agrin
  • Laminin
  • Nerve Tissue Proteins
  • SNARE Proteins
  • Synaptotagmin II
  • UNC13B protein, human
  • VAMP1 protein, human
  • Vesicle-Associated Membrane Protein 1
  • laminin alpha5
  • Acetylcholine