The Clinical, Myopathological, and Genetic Analysis of 20 Patients With Non-dystrophic Myotonia

Quanquan Wang,Qi Bing,Jing Hu,Nan Li,Hongrui Shen,Zhe Zhao

doi:10.3389/fneur.2022.830707

Quanquan Wang, Qi Bing + Show 4 more

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https://doi.org/10.3389/fneur.2022.830707

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Abstract

IntroductionNon-dystrophic myotonias (NDMs) are skeletal muscle ion channelopathies caused by CLCN1 or SCN4A mutations. This study aimed to describe the clinical, myopathological, and genetic analysis of NDM in a large Chinese cohort.MethodsWe reviewed the clinical manifestations, laboratory results, electrocardiogram, electromyography, muscle biopsy, genetic analysis, treatment, and follow-up of 20 patients (from 18 families) with NDM.ResultsCases included myotonia congenita (MC, 17/20) and paramyotonia congenita (PMC, 3/20). Muscle stiffness and hypertrophy, grip and percussion myotonia, and the warm-up phenomenon were frequently observed in MC and PMC patients. Facial stiffness, eye closure myotonia, and cold sensitivity were more common in PMC patients and could be accompanied by permanent weakness. Nine MC patients and two PMC patients had cardiac abnormalities, mainly manifested as cardiac arrhythmia, and the father of one patient died of sudden cardiac arrest. Myotonic runs in electromyography were found in all patients, and seven MC patients had mild myopathic changes. There was no difference in muscle pathology between MC and PMC patients, most of whom had abnormal muscle fiber type distribution or selective muscle fiber atrophy. Nineteen CLCN1 variants were found in 17 MC patients, among which c.795T>G (p.D265E) was a new variant, and two SCN4A variants were found in three PMC patients. The patients were treated with mexiletine and/or carbamazepine, and the symptoms of myotonia were partially improved.ConclusionsMC and PMC have considerable phenotypic overlap. Genetic investigation contributes to identifying the subtype of NDM. The muscle pathology of NDM lacks specific changes.

Highlights

Non-dystrophic myotonias (NDMs) are skeletal muscle ion channelopathies caused by CLCN1 or SCN4A mutations
Facial stiffness and eye closure myotonia were observed in all patients with paramyotonia congenita (PMC) and could be accompanied by myotonia in the tongue, throat, and neck muscles, while facial stiffness was observed in two patients with myotonia congenita (MC)
Three patients had MC accompanied by myalgia, and one patient had PMC accompanied by permanent weakness

Summary

Introduction

Non-dystrophic myotonias (NDMs) are skeletal muscle ion channelopathies caused by CLCN1 or SCN4A mutations. Non-dystrophic myotonias (NDMs) are a group of skeletal muscle disorders that have myotonia as their common feature, in reference to a delayed muscle relaxation after voluntary or evoked muscle contraction [1]. NDMs are different from dystrophic myotonias (DMs) because of the absence of muscle atrophy and systemic features [2–4]. The typical clinical features of patients with MC include muscle stiffness, grip and percussion myotonia, and the warm-up phenomenon (myotonia relieved after repeated activity). Patients with PMC show cold sensitivity, exercise-induced myotonia, myotonia worsening after repetitive activity, episodic weakness, and onset before the age of 10. SCM is clinically rare and has some “atypical” clinical manifestations that are lack of cold sensitivity and episodic weakness, including potassium-aggravated myotonia, fluctuating myotonia, permanent myotonia, and acetazolamide-induced myotonia [2, 5–7]. The clinical symptoms are sometimes atypical, which makes it difficult to distinguish the clinical phenotype of NDMs

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