Guidelines on clinical presentation and management of nondystrophic myotonias

Stunnenberg, Bas C.; LoRusso, Samantha; Arnold, W. David; Barohn, Richard J.; Cannon, Stephen C.; Fontaine, Bertrand; Griggs, Robert C.; Hanna, Michael G.; Matthews, Emma; Meola, Giovanni; Sansone, Valeria; Trivedi, Jaya; Engelen, B.G.M. van; Vicart, Savine; Statland, Jeffrey

doi:10.1002/mus.26887

Cited by 73 publications

(109 citation statements)

References 138 publications

(208 reference statements)

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“…CLCN1-myotonias are usually characterized by a warm-up phenomenon, worsening of myotonia under low temperature environment, and more prominent myotonia at lower limbs. Temporary weakness and segmental muscle hypertrophy occur mainly in patients with BMC [2,[10][11][12]. On the other hand, patients with PMC typically show worsening of their myotonia after repetitive movements, and under low-temperature environment.…”

Section: Supplementary Informationmentioning

confidence: 99%

Non-dystrophic myotonias: clinical and mutation spectrum of 70 German patients

et al. 2020

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Introduction Non-dystrophic myotonias (NDM) are heterogeneous diseases caused by mutations in CLCN1 and SCN4A. The study aimed to describe the clinical and genetic spectrum of NDM in a large German cohort. Methods We retrospectively identified all patients with genetically confirmed NDM diagnosed in our center. The following data were analyzed: demographics, family history, muscular features, cardiac involvement, CK, EMG, genotype, other tested genes, treatment perceived efficacy. Results 70 patients (age 40.2 years ± 14.9; 52.8% males) were included in our study (48 NDM-CLCN1, 22 NDM-SCN4A). The most frequent presenting symptoms were myotonia (NDM-CLCN1 83.3%, NDM-SCN4A 72.2%) and myalgia (NDM-CLCN1 57.4%, NDM-SCN4A 52.6%). Besides a more prominent facial involvement in NDM-SCN4A and cold-sensitivity in NDM-CLCN1, no other significant differences were observed between groups. Cardiac arrhythmia or conduction defects were documented in sixNDM-CLCN1 patients (three of them requiring a pacemaker) and one patient with NDM-SCN4A. CK was normal in 40% of patients. Myotonic runs in EMG were detected in 89.1% of CLCN1 and 78.9% of SCN4A. 50% of NDM-CLCN1 patients had the classic c.2680C>T (p.Arg894*) mutation. 12 new genetic variants are reported. About 50% of patients were not taking any anti-myotonic drug at the last follow-up. The anti-myotonic drugs with the best patient’s perceived efficacy were mexiletine and lamotrigine. Conclusion This study highlights the relevant clinical overlap between NDM-CLCN1 and NDM-SCN4A patients and warrants the use of early and broad genetic investigation for the precise identification of the NDM subtype. Besides the clinical and genetic heterogeneity, the limited response to current anti-myotonic drugs constitutes a continuing challenge.

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Section: Supplementary Informationmentioning

confidence: 99%

Non-dystrophic myotonias: clinical and mutation spectrum of 70 German patients

et al. 2020

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“…Conversely, new genes associated with PP (often with additional clinical features) have been reported, e.g., ATP1A2, KCNJ5, RYR1, mATP6, and mATP8. In addition, guidelines on clinical presentation and management of NDMs have been recently published by a panel of international experts (1).…”

Section: Editorial On the Research Topic New Insights In Skeletal Musmentioning

confidence: 99%

Editorial: New Insights in Skeletal Muscle Channelopathies - A Rapidly Expanding Field

2020

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“…The treatment of these diseases is mainly symptomatic, aimed at reducing muscle excitability in NDM or modifying triggers of paralytic attacks. In most countries, the sodium channel blocker, mexiletine, is considered the first drug choice for treatment of myotonia, whatever the culprit gene [4]. Other sodium channel blockers were reported efficient.…”

Section: Introductionmentioning

confidence: 99%

Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine

Desaphy

Altamura

Vicart

et al. 2021

JND

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Background: Skeletal muscle ion channelopathies include non-dystrophic myotonias (NDM), periodic paralyses (PP), congenital myasthenic syndrome, and recently identified congenital myopathies. The treatment of these diseases is mainly symptomatic, aimed at reducing muscle excitability in NDM or modifying triggers of attacks in PP. Objective: This systematic review collected the evidences regarding effects of pharmacological treatment on muscle ion channelopathies, focusing on the possible link between treatments and genetic background. Methods: We searched databases for randomized clinical trials (RCT) and other human studies reporting pharmacological treatments. Preclinical studies were considered to gain further information regarding mutation-dependent drug effects. All steps were performed by two independent investigators, while two others critically reviewed the entire process. Results: For NMD, RCT showed therapeutic benefits of mexiletine and lamotrigine, while other human studies suggest some efficacy of various sodium channel blockers and of the carbonic anhydrase inhibitor (CAI) acetazolamide. Preclinical studies suggest that mutations may alter sensitivity of the channel to sodium channel blockers in vitro, which has been translated to humans in some cases. For hyperkalemic and hypokalemic PP, RCT showed efficacy of the CAI dichlorphenamide in preventing paralysis. However, hypokalemic PP patients carrying sodium channel mutations may have fewer benefits from DCP compared to those carrying calcium channel mutations. Few data are available for treatment of congenital myopathies. Conclusions: These studies provided limited information about the response to treatments of individual mutations or groups of mutations. A major effort is needed to perform human studies for designing a mutation-driven precision medicine in muscle ion channelopathies.

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Guidelines on clinical presentation and management of nondystrophic myotonias

Cited by 73 publications

References 138 publications

Non-dystrophic myotonias: clinical and mutation spectrum of 70 German patients

Non-dystrophic myotonias: clinical and mutation spectrum of 70 German patients

Editorial: New Insights in Skeletal Muscle Channelopathies - A Rapidly Expanding Field

Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine

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