SCN2A Related Early Onset Epileptic Encephalopathy Responsive to Phenobarbital (P2.231)

BACKGROUND: Voltage gated sodium (Nav) channels are critical regulators of neuronal excitability. Genes for the alpha-subunits of three of the main CNS sodium channel subtypes - SCN1A, SCN2A, and SCN3A - are all located on chromosome 2q24.CASE: A full-term boy with an unremarkable pre- and peri-natal history presented at one month of age with unusual movements that had onset on day of life two. Exam was notable for lack of visual attention, hypotonia, and hyperreflexia. EEG background was characterized by invariant burst-suppression including multifocal spikes, and ictal episodes with bicycling movements associated with buildups of rhythmic activity and epileptic spasms in clusters with corresponding diffuse high amplitude slow waves followed by attenuation and overriding beta activity. Following negative imaging and metabolic studies, chromosomal microarray identified 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. At two months of age, EEG background was normal other than rare sharp waves. At 6-month follow-up there were no recurrent seizures and only mild residual hypotonia.CONCLUSIONS: Early onset epileptic encephalopathy (EOEE), with neonatal seizures, burst-suppression on EEG, and reversibility on phenobarbital, is part of the enlarging spectrum of Nav channelopathies. The diagnosis at age one month, related to the time at which parents brought the child to medical attention, allowed for an unusual opportunity to view the early natural history of this disorder and remarkable responsivity to barbiturate therapy. The clinical and EEG response to phenobarbital therapy implicates the epilepsy itself as the cause of the encephalopathy. Clinical follow-up will allow for assessment of long-term outcome. Disclosure: Dr. Baumer has nothing to disclose. Dr. Peters has nothing to disclose. Dr. Achkar has nothing to disclose. Dr. Pearl has nothing to disclose.