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Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome

Lookup NU author(s): Professor Roger Whittaker, Dr Boglarka Bansagi, Professor Rita HorvathORCiD, Professor Hanns Lochmuller


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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 metadata

Author(s): Whittaker RG, Herrmann DN, Bansagi B, Hasan BAS, Lofra RM, Logigian EL, Sowden JE, Almodovar JL, Littleton JT, Zuchner S, Horvath R, Lochmuller H

Publication type: Article

Publication status: Published

Journal: Neurology

Year: 2015

Volume: 85

Issue: 22

Pages: 1964-1971

Print publication date: 01/12/2015

Online publication date: 30/10/2015

Acceptance date: 06/08/2015

ISSN (print): 0028-3878

ISSN (electronic): 1526-632X

Publisher: Lippincott Williams & Wilkins


DOI: 10.1212/WNL.0000000000002185


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Funder referenceFunder name
CMT Association
JPB Foundation
MRC Centre for Neuromuscular Diseases
309548European Research Council
98482Medical Research Council UK
305121European Union
305444European Union
G1000848Medical Research Council (UK)
G102037Wellcome Trust
G1002274Medical Research Council UK
U54NS065712Inherited Neuropathies Consortium Rare Disease Clinical Research Network, National Institute of Neurological Disorders and Stroke