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Research Article: Genotype–Phenotype Analysis of Children with Epilepsy Referred for Whole-Exome Sequencing at a Tertiary Care University Hospital

Date Published: 2023-08-01

Abstract:
Background: Despite the high consanguinity rates, data on genetic epilepsy in Saudi Arabia is limited. The objective of the current study was to characterize genetic mutations associated with epilepsy in pediatric patients and describe their phenotypic presentations. Methods: A retrospective chart review was conducted among children presented with epilepsy in one center in Saudi Arabia between 2015 and 2018. Only those who had undergone genetic testing were included. Results: A total of 45 patients had positive whole-exome sequencing (WES) genetic testing with 37 mutations. Six mutations (SCN1A, DENND5A, KCNQ2, ACY1, SCN2A, and PCDH19) were repeated in 15 patients, with largely heterogeneous phenotypic presentations in patients with the same mutation. Several mutations are reported for the first time in Saudi Arabia. The median age at epilepsy onset was four months. Consanguineous parents and family history of epilepsy were frequent (31.8% and 33.3%, respectively). Developmental delay (44.4%), cognitive delay (42.2%), language delay (40.0%), behavioral features (28.9%), and microcephaly (20.0%) were frequent presentations. At initial diagnosis, 68.9% of EEG and 48.9% of brain MRI were abnormal. The most currently used antiseizure medications (ASMs) were levetiracetam (48.9%), topiramate (28.9%), and valproic acid (20.0%). Approximately 60% of the patients were controlled with (47.6%) or without (11.9%) ASMs, and three (7.1%) patients died. Conclusions: Multiple mutations among children with epilepsy are reported in one hospital in Saudi Arabia, with the majority reported for the first time. The current findings highlight the importance of doing genetic testing for the evaluation of childhood epilepsy.

Introduction:
Epilepsy is defined as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition manifested with at least one epileptic seizure [1]. The incidence of epilepsy in children worldwide is estimated to be between 35 and 187 new cases per 100,000 and is consistently highest in the first year of life [2,3]. The prevalence of epilepsy in children ranges between 3 and 7 active cases per…

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