Mongraph: Electrodiagnostic Evaluation of Congenital Myasthenic Syndromes-Article

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This 2025 AANEM monograph by Ricardo A. Maselli reviews the electrodiagnostic (EDX) evaluation of congenital myasthenic syndromes (CMS), which are rare genetic disorders affecting neuromuscular (NM) transmission, leading to weakness and fatigability. Although CMS prevalence is about 9 per million children, these patients commonly appear in specialized EDX labs. CMS involves mutations in over 35 genes affecting presynaptic, synaptic, or postsynaptic proteins critical for NMJ function.<br /><br />EDX testing, especially repetitive nerve stimulation (RNS) at slow (2–3 Hz) and fast rates, is central for detecting NM transmission failure—a hallmark of CMS. Slow-rate RNS reveals decrement in compound muscle action potentials (CMAPs) due to synaptic vesicle depletion and calcium accumulation at nerve terminals, often showing a characteristic U-shaped response in postsynaptic CMS. Fast-rate RNS can unmask subtle defects or frequency-dependent transmission failures, as seen in some CMS forms involving sodium channel dysfunction or acetylcholinesterase deficiency. Single-fiber EMG (SFEMG) is highly sensitive for detecting NM transmission abnormalities by measuring increased jitter and blocking, especially when decrements on RNS are subtle or absent.<br /><br />The monograph classifies CMS by protein defect localization: presynaptic (e.g., choline acetyltransferase, SNARE proteins, mitochondrial-related), synaptic (e.g., collagen Q, laminins), and postsynaptic (acetylcholine receptor subunits, rapsyn, sodium channels). Each subtype has distinctive EDX features. For instance, COLQ mutations cause prolonged endplate potentials, repetitive CMAPs, and frequency-dependent decrement with VGSC inactivation. Mutations in SNARE proteins and Ca2+ sensors yield Lambert-Eaton myasthenic syndrome (LEMS)-like facilitation patterns. Postsynaptic receptor defects show decremental CMAP responses similar to acquired myasthenia gravis, with slow- and fast-channel syndromes exhibiting characteristic repetitive responses and spectral changes.<br /><br />EDX findings vary between patients and treatment status, requiring comprehensive assessment of proximal and distal muscles and multiple techniques. Preconditioning RNS at 10 Hz for 5 minutes can reveal subtle transmission defects in presynaptic synthesis disorders. Overall, EDX testing guides diagnosis, genetic testing strategies, and targeted therapeutics, improving outcomes. The monograph includes detailed physiology, clinical correlations, illustrative EDX tracings, and a summary table linking gene defects to electrophysiological patterns, serving as a practical guide for clinicians managing CMS.

Keywords

congenital myasthenic syndromes

electrodiagnostic evaluation

neuromuscular transmission

repetitive nerve stimulation

single-fiber EMG

presynaptic protein defects

synaptic protein defects

postsynaptic receptor mutations

compound muscle action potentials

genetic mutations in CMS