Abstract
SCN4A gene mutations cause a number of neuromuscular phenotypes including myotonia. A subset of infants with myotonia‐causing mutations experience severe life‐threatening episodic laryngospasm with apnea. We have recently identified similar SCN4A mutations in association with sudden infant death syndrome. Laryngospasm has also been proposed as a contributory mechanism to some cases of sudden unexpected death in epilepsy (SUDEP). We report an infant with EEG‐confirmed seizures and recurrent apneas. Whole‐exome sequencing identified a known pathogenic mutation in the SCN4A gene that has been reported in several unrelated families with myotonic disorder. We propose that the SCN4A mutation contributed to the apneas in our case, irrespective of the underlying cause of the epilepsy. We suggest this supports the notion that laryngospasm may contribute to some cases of SUDEP, and implicates a possible shared mechanism between a proportion of sudden infant deaths and sudden unexpected deaths in epilepsy.
Highlights
The SCN4A gene codes for the alpha sub‐unit of the voltage‐gated sodium channel Nav1.4, which is essential for muscle membrane excitability and contraction.[1]
The father denied any symptoms of myopathy and/or myotonia, and none were demonstrated on clinical examination
Several cases of infantile SCN4A myotonia with laryngospasm and apnea have been reported to be erroneously diagnosed as generalized seizures, delaying appropriate therapy.[6]
Summary
The SCN4A gene codes for the alpha sub‐unit of the voltage‐gated sodium channel Nav1.4, which is essential for muscle membrane excitability and contraction.[1]. Infants with SCN4A‐related myotonia can appear outwardly healthy but present acutely with recurrent episodes of generalized stiffening of the trunk and limbs, apnea, and cyanosis (due to respiratory and laryngeal muscle myotonia‐causing laryngospasm) which may be accompanied by bradycardia and loss of consciousness. This specific myotonic phenotype has been named severe neonatal episodic laryngospasm[5] (SNEL). An erroneous diagnosis of generalized epilepsy is frequently made in these infants.[6] Events can be life‐threatening or “near miss” with several infants requiring ventilation and prolonged ITU admissions.[5,7] Such acute life‐threatening events recently led us to investigate SCN4A gene mutations in cases of sudden infant death. Laryngospasm has been proposed as a contributory mechanism in sudden unexpected death in epilepsy (SUDEP).[9,10,11,12]
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