Single-fiber electromyography-based diagnosis of CACNA1A mutation in children: A potential role of the electrodiagnosis in the era of whole exome sequencing.

Introduction: A loss-of-function mutation in CACNA1A, which encodes P/Q-type Ca channels, causes various diseases. As most of the Ca channels at neuromuscular junctions are of the P/Q type, patients with loss-of-function CACNA1A mutations exhibit disturbed neuromuscular transmission. The associated jitters and blocking in such patients can be detected by single-fiber electromyography (SFEMG).
Cases: We report two cases with different phenotypes, which were predicted to harbor loss-of-function mutations of CACNA1A, by using axonal stimulation SFEMG. One case involved a 2-year-old boy with episodic ataxia type 2. The other case involved a 7-year-old girl diagnosed with epileptic encephalopathy. SFEMG results revealed jitters and blocking in both cases. Moreover, whole exome sequencing (WES) revealed a heterozygous CACNA1A mutation, c.5251C>T, p.Arg1751Trp, in the former case and a novel de novo CACNA1A mutation, c.2122G>A, p.Val708Met, in the latter.
Conclusions: Our cases indicate that SFEMG is a potentially useful diagnostic tool for patients with CACNA1A mutation, especially in pediatric cases where trio analysis is difficult or novel mutations are present.
(Copyright © 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)