Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome

Neurology. 2015 Dec 1;85(22):1964-71. doi: 10.1212/WNL.0000000000002185. Epub 2015 Oct 30.


Objectives: To describe the clinical and electrophysiologic features of synaptotagmin II (SYT2) mutations, a novel neuromuscular syndrome characterized by foot deformities and fatigable ocular and lower limb weakness, and the response to modulators of acetylcholine release.

Methods: We performed detailed clinical and neurophysiologic assessment in 2 multigenerational families with dominant SYT2 mutations (c.920T>G [p.Asp307Ala] and c.923G>A [p.Pro308Leu]). Serial clinical and electrophysiologic assessments were performed in members of one family treated first with pyridostigmine and then with 3,4-diaminopyridine.

Results: Electrophysiologic testing revealed features indicative of a presynaptic deficit in neurotransmitter release with posttetanic potentiation lasting up to 60 minutes. Treatment with 3,4-diaminopyridine produced both a clinical benefit and an improvement in neuromuscular transmission.

Conclusion: SYT2 mutations cause a novel and potentially treatable complex presynaptic congenital myasthenic syndrome characterized by motor neuropathy causing lower limb wasting and foot deformities, with reflex potentiation following exercise and a uniquely prolonged period of posttetanic potentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / analogs & derivatives
  • 4-Aminopyridine / pharmacology
  • 4-Aminopyridine / therapeutic use
  • Adolescent
  • Adult
  • Aged
  • Amifampridine
  • Child
  • Electrophysiological Phenomena
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Myasthenic Syndromes, Congenital / drug therapy
  • Myasthenic Syndromes, Congenital / genetics
  • Myasthenic Syndromes, Congenital / physiopathology*
  • Potassium Channel Blockers / pharmacology
  • Potassium Channel Blockers / therapeutic use
  • Pyridostigmine Bromide / pharmacology
  • Pyridostigmine Bromide / therapeutic use
  • Reflex / drug effects
  • Reflex / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Synaptotagmin II / genetics*
  • Young Adult


  • Potassium Channel Blockers
  • SYT2 protein, human
  • Synaptotagmin II
  • 4-Aminopyridine
  • Pyridostigmine Bromide
  • Amifampridine