Genetic spectrum of Developmental and Epileptic Encephalopathies

Epileptic encephalopathies (EE),are a group of disorders characterised by drug resistant epilepsy and electroencephalogram (EEG) abnormalities that may result in developmental delay .Genetically its highly heterogeneous group. Method: This is retrospective study of children with EE from the participating hospitals.Children with EE with genetic diagnosis(pathogenic/likely pathogenic variants) were included, children with perinatal insult /structural brain malformation were excluded .Clinical details noted,Genetic diagnosis done by NGS in commercial labs. Results - Total of 15 patients (9 Males 6 Females) included. The age of onset of seizures ranged from1week to14months (average 6 months). Consanguinity was present in 6/15( 40% )of the cases, (in all with autosomal recessive inheritance).The predominant types of seizures were focal and tonic seizures. Epilepsy syndrome was classified in 7children as ohtahara (3),west syndrome (3) and LGS (1) .The most prevalent EEG pattern was the epileptic encephalopathy (70%) .The brain MRI was normal 12/15(80%) ,2/15 had brain atrophy . All were delayed in development (speech delay was seen in all ,motor delay in 10/15(66%). Commonest genetic cause found was SCN1A mutation (5/15), followed by SCN2A (2/15) and one each of KCNT1,STXBP1, PCDH19, ITPA, NGLY1, ARFGEF2, SLC1A4,CACNA1. Autosomal dominant was the commonest inheritance 10/15 (66%) .The treatment with antiseizure medications ranged from 3medications to more than 5medications (66%) .The majority of patients had poor seizure control, while 1 child expired at 1.5 yrs .Genetic diagnosis helped in management (choosing the ASM ) of 3/15 children. Conclusion - Genetic diagnosis in EE is important for personalised management, prognosis, and genetic counselling.
Keywords: developmental epileptic encephalopathy, next generation sequencing ,genetics