SCN2A-Related Early-Onset Epileptic Encephalopathy Responsive to Phenobarbital

Abstract

Voltage-gated sodium channels (Nav) are critical regulators of neuronal excitability. Genes for the α-subunits of three sodium channel subtypes-SCN1A, SCN2A, and SCN3A-are all located on chromosome 2q24. A full-term boy with an unremarkable birth history presented at 1 month of age with unusual movements that had started on day of life 2. Exam was notable for lack of visual attention, hypotonia, and hyperreflexia. Electroencephalogram (EEG) showed an invariant burst suppression with multifocal spikes, ictal episodes with bicycling movements associated with buildups of rhythmic activity, and epileptic spasms. Work-up revealed a 1.77-Mb duplication at locus 2q24.3, encompassing the entirety of SCN2A and SCN3A, but not SCN1A. Phenobarbital led to rapid resolution of the clinical seizures and EEG background normalized other than rare sharp waves. Early-onset epileptic encephalopathy (EOEE), with neonatal seizures, burst suppression, and reversibility with phenobarbital, is part of the enlarging spectrum of Nav channelopathies. The delayed diagnosis provided an unusual opportunity to view the early natural history of this disorder and its remarkable responsiveness to barbiturate therapy. The clinical and EEG response to phenobarbital implicates seizures as the cause of the encephalopathy.