The latter effect may form the basis for Ca<sup>2+</sup>-dependent Na<sup>+</sup> channel dysregulation in SCN4Achannelopathies associated with cold- and K<sup>+</sup>-aggravated myotonias.
In this study, we investigated whether cardiac arrhythmias or channelopathies such as Brugada syndrome can be part of the clinical phenotype associated with SCN4A variants and whether patients with Brugada syndrome present with non-dystrophic myotonia or periodic paralysis and related gene mutations.
In 2 patients (1%), EMG studies demonstrated myotonia, and muscle biopsy showed mild myopathic features; 1 patient had myotonic dystrophy type 2, and the other had SCN4A-related muscle channelopathy.
In this report, for the first time, we associated the genetic variability of SCN4A with the development of essential tremor, which adds ET to the growing list of neurological channelopathies.
The relationship between two phenotypes and SCN4A has been confirmed with additional cases that remain extremely rare: severe neonatal episodic laryngospasm mimicking encephalopathy, which should be actively searched for since patients respond well to sodium channel blockers; congenital myasthenic syndromes, which have the particularity to be the first recessive Nav1.4 channelopathy.
Mutations in the skeletal muscle channel (SCN4A), encoding the Nav1.4 voltage-gated sodium channel, are causative of a variety of muscle channelopathies, including non-dystrophic myotonias and periodic paralysis.
We describe the first distinctive clinical genotype-phenotype correlation within NaCh: a strictly isolated eyelid closure myotonia associated with the L250P mutation in SCN4A.
Hypokalaemic periodic paralysis (HypoKPP) is a skeletal muscle channelopathy caused by mutations in calcium (CACNA1S) and sodium (SCN4A) channel subunits.
This phenotype is clearly different from classical paramyotonia congenita Eulenburg, which has been shown to be a sodium channelopathy resulting from mutations in the gene for the alpha-subunit of the human skeletal muscle sodium channel gene (SCN4A).