PP01.1 – 2565: Next generation sequencing analysis in neonatal/early epileptic encephalopathy

Abstract

Objective Epileptic encephalopathy (EE) term describes epilepsy syndromes in which seizures and epileptiform electroencephalographic abnormalities are considered to contribute to progressive cerebral dysfunction. A subset of all the EEs that still await an etiological explanation, particularly those with onset of seizures within the first year of life. In this study genetic backround of neonatal/early infantile EE was investigated by next generation sequencing (NGS) analysis. Methods Thirty cases who had refractory seizures with neonatal or early infantile onset were prospectively included in this study. Three cases had history of hospitalization in neonatal unit due to meconium aspiration syndrome, and four cases also had cyanosis and/or transient respiratory distress following the labor. All cases had normal metabolic work up including serum lactic acid, pyruvic acid, aminoacid and carnitine levels, biotinidase activity and urine organic acids. Their cranial magnetic resonance imaging findings were normal except cerebral atrophy. Their karyotype analyses were normal. None of them had antiquitin gene mutation. Mutations in 16 genes (ARX, CDKL5, CNTNAP2, FOLR1, FOXG1, GRPR, LAMC3, MBD5, MECP2, PCDH19, PNKP, SCN1A, SCN1B, SCN2A, STXBP1, KCNQ2) were examined with NGS method in our cases. Results Ages ranged between 6–204 (62.5±51.6) months. Parental consanguinity was found in 11 of 30 cases (36%). Seizures started between 1–270 (91.7±80.25) days of life, eleven cases had seizures with neonatal onset. Infantile spasms were the predominant seizure type in our group consisting of 16 of 30 cases. All of them were treated with at least two anticonvulsant drugs. Cranial magnetic resonance imaging was normal in half of the cases, the reminder had cortical or cerebellar atrophy. The results of NGS analysis were discussed with the literature. Conclusion We believe that NGS screening will soon contribute to pediatric neurologists to diagnose children with epilepsies of unknown etiology.