INTRODUCTION: Paediatric onset refractory epilepsies are devastating conditions characterised by progressive cerebral dysfunction associated with abnormal electroencephalographic(EEG) patterns leading to cognitive, behaviour and neurological deficits.

OBJECTIVE:

1) To identify genetic causes of paediatric onset refractory epilepsies

2) To understand its role in patient management.

METHODS: 129 children who underwent next generation sequencing for refractory epilepsies were enrolled in the study. Detailed clinical history along with EEG description and neuroimaging were correlated with genetic variants to evaluate their clinical significance.

RESULTS: 10/129, 86/129 and 33/129 belonged to neonatal, infantile and childhood onset refractory epilepsies respectively. Causative epileptic genes were found in 66.6%(86/129).

In the neonatal period 80%(8/10) showed gene positivity. Ohtahara syndrome(6/10) was the commonest presentation. The genetic variants were STXBP1,ALDH7A1,CDKL5,TUBB3,BRAT1 and KCNQ2.

West syndrome was the commonest phenotype followed by Febrile Seizure Plus/Dravet Syndrome in infantile age group. 63.9%(55/86) showed causative genes. EIEE related genes(SPTAN1,SZT2,HCN1,SIK1) accounted for 32.7%(18/55). SCN-related genes(SCN1A,SCN1B,SCN9A) were the second common genotype with 17.7%(15/55). Metabolic aetiologies were detected in 18%(10/55) such as HCFC1(methylmalonic-acidemia),SLC2A1(GLUT1 deficiency),NGLY1(congenital disorder of glycosylation) and others like MTATP6,TPP1,POLG. Structural cause was noted in 10%(6/55) (LAMB1,TUBG1,PAFAH1B1,LAMC3,TSC2,WDR62).

Childhood onset epilepsies had varied phenotype such as focal epilepsies, progressive myoclonic epilepsy and FIRES. 67.7%(23/33) showed causative genes like DEPDC5,CNTNAP2,NHLRC1,RANBP2,MT-TL1.

Treatment could be optimised in 5/8, 25/55 and 7/23 in neonatal, infantile and childhood onset epilepsies respectively, with a total of 37/86(43%).

CONCLUSION:

• Yield of genetics was 66% in unexplained refractory epilepsies
• Metabolic encephalopathies accounted for 18%.
• Treatment modifications with improved seizure outcomes were possible in 43%.