Abstracts

Rationale: 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. Ohtahara syndrome, or early infantile epileptic encephalopathy with predominantly tonic seizures and burst-suppression EEG, typically has an ominous prognosis. We describe a case of Ohtahara syndrome encompassing duplication of SCN2A and 3A with a positive outcome.Methods: The proband is a full-term male neonate with an unremarkable birth and perinatal history who presented at one month of age with unusual movements that had started on the second day of life. Clinical, EEG, and genomic microarray results were consistent with Ohtahara syndrome but an unexpected response to therapy.Results: Exam was notable for lack of visual attention, hypotonia, and hyperreflexia. EEG background showed an invariant burst-suppression pattern with multifocal spikes, and ictal events were tonic seizures with stiffening and associated bicycling movements as well as epileptic spasms (Figure 1). Following normal brain 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 and EEG background normalized other than rare sharp waves (Figure 2). At 6-month follow-up there were no recurrent seizures, and only mild residual hypotonia.Conclusions: Early infantile epileptic encephalopathy (EIEE, or Ohtahara syndrome) responsive to 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.