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Abstract
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.
GLOSSARY
- APB=
- abductor pollicis brevis;
- CMAP=
- compound muscle action potential;
- CMS=
- congenital myasthenic syndrome;
- CMSS=
- Congenital Myasthenic Syndrome Scale;
- 3,4-DAP=
- 3,4-diaminopyridine;
- LEMS=
- Lambert-Eaton myasthenic syndrome;
- MRC=
- Medical Research Council;
- MVC=
- maximum voluntary contraction;
- RNS=
- repetitive nerve stimulation;
- SYT2=
- synaptotagmin II;
- TA=
- tibialis anterior;
- VGCC=
- voltage-gated calcium channel
Footnotes
↵* These authors contributed equally to this work.
↵‡ These authors contributed equally to this work.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received June 10, 2015.
- Accepted in final form August 6, 2015.
- © 2015 American Academy of Neurology
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