DefinePK

Abstract

Objective: To seek genotype-phenotype correlates of developmental and epileptic encephalopathies (DEE) in less than 2 years of age and yield genetic testing. 
Methodology: A retrospective cross-sectional study was performed on children presenting to the Department of Pediatric Neurology CH&UCHS with a seizure onset of < 2 years of age, EEG studies showing epileptic encephalopathy, refractory epilepsy, and neurodevelopmental impairment between the period of March 2021-2022. Whole exome sequencing (WES) was performed and yield1was based on the expression of pathogenic or likely pathogenic variants. 
Results: Out of the total study population (57), 64.9% (37) were male participants. Early onset seizures were noted in 54.4% (31), delayed milestones in 89.5% (51), regression of achieved milestones in 12.3% (7), and 86.0% (49) were born to consanguineous parents. Pathogenic mutations were identified in 22% of participants (38.6). Nine causative genes i.e., SLC13A5, SCN1B, CNPY3, PIGS, ALDH7A, AP3B2, GAD1, TBCID24, and PARS2 were found. Male gender (p = 0.031), earlier age of seizure onset (p = 0.0001), consanguinity (p = 0.014) and drug-resistant epilepsy (p = 0.006) was significant among patients with identified genetic mutations. The phenotype-genotype correlation identified Ohtahara syndrome in 14.2% of suspected Ohtahara participants, early myoclonic encephalopathy in 40.0%, West syndrome in 22.22%, Dravet Syndrome in 40.0%, and primary DEE in 47.61%. Out of all, 1 participant (4.5%) had a syndrome with neuro metabolic etiology. 
Conclusion: Whole exome sequencing is an effective diagnostic tool for patients with developmental and epileptic encephalopathy. Genotype-phenotype correlations help predict the clinical progression & treatment efficacy.