G150 Aetiological investigations and treatment outcomes in a prospective population-based cohort of children with epilepsy <3 years

Objectives To report the yield from all aetiological investigations in a prospective population–based cohort of children presenting with new–onset epilepsy To calculate the impact of gene panel testing on diagnostic yield To calculate the impact of Whole Genome Sequencing (WGS) on diagnostic yield in drug–resistant epilepsy (DRE) cases Methods Early-onset epilepsy cases ( Capture-recapture analysis was used to estimate missing cases. Follow-up was for minimum 12 months. Presence or absence of DRE and global development delay (GDD) at latest follow-up was recorded for each case. All cases without identified aetiology after neuroimaging and targeted genetic/metabolic tests were tested on a 104 gene epilepsy panel. Those with DRE who were negative on gene panel testing underwent WGS. Results Population statistics for the region were: Total population (2017) 3.00 million; mean births per year (2011–2016) 31 000. 229 patients were identified. Using capture-recapture the estimated total was 236. The estimated incidence of epilepsy At latest follow-up 83 (36%) had DRE and 112 (49%) had GDD. 75 (33%) patients had aetiology identified prior to gene panel testing. Of these 37 (49%) were structural, 32 (43%) genetic (6 trisomy, 18 microdeletion/duplication, 8 single gene disorder), 4 (5%) metabolic, 1 immune, and 1 infectious. A further 42 (18%) had a diagnosis made through gene panel testing, increasing overall diagnostic yield to 51%. Of the 83 DRE patients, 41 (49%) had an aetiological diagnosis prior to gene panel testing. A further 21 had a diagnosis through gene panel testing (cumulative yield=75%) and another 9 had a diagnosis through WGS (86%). Conclusion One in 400 children develops epilepsy before their third birthday. One third develop drug resistance and half have GDD. With extensive genetic testing >85% of children with DRE have a cause identified.