Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome

Roger G. Whittaker, David N. Herrmann, Boglarka Bansagi, Bashar Awwad Shiekh Hasan, Robert Muni Lofra, Eric L. Logigian, Janet E. Sowden, Jorge L. Almodovar, J. Troy Littleton, Stephan Zuchner, Rita Horvath, Hanns Lochmüller

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1964-1971
Number of pages8
Issue number22
StatePublished - Dec 1 2015

ASJC Scopus subject areas

  • Clinical Neurology


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