Whole exome sequencing with targeted gene analysis and epilepsy after
acute symptomatic neonatal seizures
Abstract
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.