200 Section - Characteristic Repetitive Compound Motor Unit Action Potentials in a Case of Slow-Channel Congenital Myasthenic Syndrome

A 39-year-old female with weakness and fatigue was referred for electrophysiologic testing. The symptoms began during pregnancy 20 years prior. She had no ocular or bulbar symptoms. Strength testing demonstrated neck extension weakness, 3/5 finger extension, and 4/5 shoulder abduction and ankle dorsiflexion.

On electrophysiologic testing, median and ulnar CMAPs demonstrated normal amplitude and latency, but had repetitive CMPAPs (R-CMAPs), suggestive of CMS. Slow repetitive stimulation of the ulnar nerve recording ADM had 20% decrement at baseline. Genetic testing identified a heterozygous missense variant of uncertain significance, CHRNB1 c.755T >A, p.(Val252Asp), and she was diagnosed with slow-channel CMS.

Discussions: CMS are a heterogeneous group of inherited disorders characterized by impaired NMJ transmission. The most common CMS variant is caused by loss-of-function CHRNE mutations and improves with pyridostigmine. Worsening of symptoms during pregnancy has been reported.
R-CMAPs are specific for slow-channel CMS from mutations in AChR subunit genes (CHRNE, CHRNA1, CHRNB1, or CHRND) and COLQ-associated AChE deficiency CMS. Gain-of-function mutations in these genes exhibit paradoxical worsening with cholinesterase inhibition.
R-CMAPs may be synaptic or neurogenic. Synaptic R-CMAPs result from continued endplate depolarization causing muscle fiber reactivations from excess acetylcholine or prolonged AChR channel opening. R-CMAPs may also occur with acetylcholinesterase inhibitor toxicity, organophosphate poisoning, and nerve hyperexcitability syndromes.

Conclusions: This case emphasizes the critical role of electrophysiological testing and recognition of R-CMAPs in the diagnosis of CMS. This can prompt appropriate genetic evaluation, prevent unnecessary treatments, and guide targeted management strategies. Understanding potential triggers for symptom exacerbation such as pregnancy supports more precise diagnosis, anticipatory guidance, and optimized care. In this case, repetitive CMAPs and a gain-of-function AChR mutation confirmed slow-channel CMS, a subtype that worsens with pyridostigmine. Recognition of this R-CMAP impacted initial treatment in this patient as pyridostigmine was avoided, and treatment with fluoxetine was initiated.