Paramyotonia congenita (PC) is a neuromuscular disorder caused by point mutations of the sodium channel gene SCN4A that leads to gating defects in the sodium channel of the muscle membranes, thus resulting in a persistent sodium influx into the sarcoplasma. Classic PC phenotype is characterised by episodes of cold-induced stiffness, prominently in the facial and upper limb muscles, exacerbated by a sustained muscular activity (paramyotonia) and followed by a variable degree of weakness. Electromyography (EMG) at rest discloses myotonic bursts and reduced Compound Muscle Action Potential (CMAP) amplitudes, while short-term forearm exercise and cooling tests induce further decrease resulting in electrical silence in some patients. Muscle paralysis, after paramyotonic attacks, may last from a few dozen minutes to 24-48 hours, thus reducing considerable quality of life and autonomy in daily activities. Among voltage-gating sodium channel blockers, mexiletine is considered the drug of choice in PC and other sodium channel myopathies.1 However, mexiletine efficacy has been investigated only in a few heterogeneous small PC series during a month-lasting follow-up. In experimental studies, flecainide, a class IC antiarrhythmic drug, appeared to be more effective than mexiletine to counteract SCN4A dysfunction.2 However, we lack long-term follow-up studies on flecainide efficiency in patients with PC with homogeneous pheno/genotype. The aim of this study was to assess the responsiveness to flecainide in a large family with classic PC phenotype by electrophysiological and quality of life evaluations.

Successful long-term therapy with flecainide in a family with paramyotonia congenita

Esposito T;
2018

Abstract

Paramyotonia congenita (PC) is a neuromuscular disorder caused by point mutations of the sodium channel gene SCN4A that leads to gating defects in the sodium channel of the muscle membranes, thus resulting in a persistent sodium influx into the sarcoplasma. Classic PC phenotype is characterised by episodes of cold-induced stiffness, prominently in the facial and upper limb muscles, exacerbated by a sustained muscular activity (paramyotonia) and followed by a variable degree of weakness. Electromyography (EMG) at rest discloses myotonic bursts and reduced Compound Muscle Action Potential (CMAP) amplitudes, while short-term forearm exercise and cooling tests induce further decrease resulting in electrical silence in some patients. Muscle paralysis, after paramyotonic attacks, may last from a few dozen minutes to 24-48 hours, thus reducing considerable quality of life and autonomy in daily activities. Among voltage-gating sodium channel blockers, mexiletine is considered the drug of choice in PC and other sodium channel myopathies.1 However, mexiletine efficacy has been investigated only in a few heterogeneous small PC series during a month-lasting follow-up. In experimental studies, flecainide, a class IC antiarrhythmic drug, appeared to be more effective than mexiletine to counteract SCN4A dysfunction.2 However, we lack long-term follow-up studies on flecainide efficiency in patients with PC with homogeneous pheno/genotype. The aim of this study was to assess the responsiveness to flecainide in a large family with classic PC phenotype by electrophysiological and quality of life evaluations.
2018
Istituto di genetica e biofisica "Adriano Buzzati Traverso"- IGB - Sede Napoli
Paramyotonia congenita (PC); sodium channel gene (SCN4A); flecainide
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/355499
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