The utility of whole exome sequencing (WES) with targeted gene analysis has been important for establishing diagnosis and prognosis of severe early-onset epileptic encephalopathies, but the contribution of pathogenic gene variants to epileptogenesis after acute symptomatic neonatal seizures is not known. We performed a case-control study of 20 trios in children with a history of acute symptomatic neonatal seizures: 10 with and 10 without post-neonatal epilepsy. We used WES and identified pathogenic de novo, transmitted, and non-transmitted variants from genes with known association with epilepsy and correlated prevalence of these variants with epilepsy outcomes. We performed a sensitivity analysis with genes associated with coronary artery disease (CAD). Among 200 known genes associated with epilepsy, we identified pathogenic variants in six children with post-neonatal epilepsy and in two children without subsequent epilepsy (OR 6.0, 95% CI 0.6-80, p=0.07). There was no difference in the number of children with pathogenic variants in CAD genes between groups. Larger studies evaluating this association may lead to a better understanding of the risk of epilepsy after acute symptomatic neonatal seizures and elucidate molecular pathways that are dysregulated after brain injury and implicated in epileptogenesis.