GENOTYPE-PHENOTYPE CORRELATIONS IN EPILEPTIC ENCEPHALOPATHY SYNDROMES IN LESS THAN 2 YEARS OF AGE: A SINGLE CENTRE EXPERIENCE: GENOTYPE-PHENOTYPE CORRELATIONS IN EPILEPTIC ENCEPHALOPATHY SYNDROMES

Saher Gul Ahdi; Waseem ur Rahman; Joveria Raza Alvi; Muhammad Azeem Ashfaq; Stephanie Efthymiou; Zia ur Rehman; Tipu Sultan; Henry Houlden

Authors

Saher Gul Ahdi Children hospital and University of Child Health Sciences
Waseem ur Rahman Children Hospital and University of Child Health Sciences
Joveria Raza Alvi Children Hospital and University of Child Health Sciences
Muhammad Azeem Ashfaq Children Hospital and University of Child Health Sciences
Stephanie Efthymiou University Collage London
Zia ur Rehman Children Hospital and University of Child Health Sciences
Tipu Sultan Children Hospital and University of Child Health Sciences
Henry Houlden University Collage London

Keywords:

developmental & epileptic encephalopathy, WWhole exome sequencing

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.

GENOTYPE-PHENOTYPE CORRELATIONS IN EPILEPTIC ENCEPHALOPATHY SYNDROMES IN LESS THAN 2 YEARS OF AGE: A SINGLE CENTRE EXPERIENCE