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Case Reports
. 2023 Nov 28:10:2329048X231216432.
doi: 10.1177/2329048X231216432. eCollection 2023 Jan-Dec.

A Novel Homozygous Variant in the CHRNE Gene in 2 Siblings with Congenital Myasthenic Syndrome

Cassie Chan  1 , Lucy Emery  2 , Caroline Maltese  2 , Ashutosh Kumar  1   3 , Ermal Aliu  4 , Sunil Naik  1   3 , Dustin Paul  1   3
Affiliations
Case Reports

A Novel Homozygous Variant in the CHRNE Gene in 2 Siblings with Congenital Myasthenic Syndrome

Cassie Chan et al. Child Neurol Open. .

Abstract

Cholinergic receptor nicotinic epsilon (CHRNE) subunit mutations cause postsynaptic type of congenital myasthenic syndrome either as a primary acetylcholine-receptor deficiency or abnormal channel kinetics in the receptor. We report a novel homozygous variant (c.322C > T, p.Pro108Ser) in the epsilon subunit causing primary acetylcholine-receptor deficiency in two siblings. Two siblings presented with fatigable weakness. Both siblings had whole exome sequencing showing a homozygous variant (c.322C > T, p.Pro108Ser) of unknown significance in the epsilon subunit. Electromyography/nerve conduction study with repetitive nerve stimulation on one sibling showed a defect in neuromuscular junction transmission. Pseudoephedrine and fluoxetine for suspected slow-channel congenital myasthenic syndrome yielded no improvement. A trial of pyridostigmine led to clinical improvement. Given the clinical presentation, consanguinity, homozygous genetic variant, and response to pyridostigmine, we rationalize the homozygous variant (c.322C > T, p.Pro108Ser) in cholinergic receptor nicotinic epsilon subunit causes the primary acetylcholine-receptor deficiency congenital myasthenic syndrome.

Keywords: CHRNE; CMS; congenital myasthenic syndrome; neuromuscular; pediatric.

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Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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