Abstracts

Rationale: The genetic causes of epilepsy are presumed to be multifactorial and are important in childhood epilepsy. Recent studies revealed that various genetic mutations linked to genetic epileptic syndromes and provided information about the mechanism of epileptogenesis, prognosis, and adequate treatment. In this study, we try to detect genetic mutations through epilepsy gene panel using next generation sequencing (NGS) in early-onset epilepsies in childhood. Methods: We retrospectively reviewed the medical records of 68 patients (female : male = 37 : 31) with early-onset (=2yr) epilepsy at Samsung Medical Center between June 2014 and April 2016. The patients with symptomatic etiologies such as structural brain lesions were excluded. We designed customized NGS-based epilepsy gene panel containing total 111 genes which included 38 candidate genes for genetic generalized epilepsy syndromes and 73 genes for other genetic epilepsy. The gene panel included the coding exons, and intro-exon boundaries using bidirectional sequencing. Results: The mean age of seizure onset was 0.6 0.45 years (range, 3 days to 2 years old). Thirty-eight patients (55.9%) had severe developmental delay and 23 patients (33.8%) had normal developments. Three sibling cases was included and 28 patients had a family history of epilepsy (n = 18) or febrile seizure (n = 10). In 34 patients (50.0%), we identified mutations which were known to be associated with genetic epilepsy disorders: SCN1A (n = 13, 38.2%), PRRT2 (n = 4, 11.8%), SCN8A (n = 3, 8.8%), PCDH19 (n = 3, 8.8%), KCNQ2 (n = 2, 5.9%), KCNT1 (n = 2, 5.9%), KCNQ3 (n = 1, 2.9%) ARX (n = 1, 2.9%), SCN9A (n = 1, 2.9%), FOXG1 (n = 1, 2.9%), KCNMA1 (n = 1, 2.9%), and CACNA1H (n = 1, 2.9%). In 18 children with presumed as Dravet syndrome clinically, 12 were confirmed to have a SCN1A mutation and 3 had a PCDH19 mutation. The other one was revealed to have a SCN8A mutation. One family was revealed to have PRRT2 mutation. Twenty-one patients with mutation were sporadic cases without family history. Conclusions: Our data demonstrated the clinical efficacy of NGS-based epilepsy gene panel for screening in not only patients with clinically suspicious of specific syndrome but also sporadic cases. NGS-based epilepsy gene panel makes another step forward in diagnosis and new therapeutic approaches of childhood intractable epilepsy. Funding: This study was not supproted by any funding.