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

Fahad A Bashiri; Rawan AlSheikh; Muddathir H Hamad; Hamad Alsheikh; Rana Abdullah Alsheikh; Amal Kentab; Najd AlTheeb; Malak Alghamdi

doi:10.3390/children10081334

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

Children (Basel). 2023 Aug 1;10(8):1334. doi: 10.3390/children10081334.

Authors

Fahad A Bashiri^{1

2}, Rawan AlSheikh³, Muddathir H Hamad², Hamad Alsheikh², Rana Abdullah Alsheikh³, Amal Kentab^{1

2}, Najd AlTheeb⁴, Malak Alghamdi^{1

5}

Affiliations

¹ Department of Pediatrics, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.
² Division of Pediatric Neurology, Department of Pediatrics, King Saud University Medical City, Riyadh 11461, Saudi Arabia.
³ Division of Pediatric Neurology, Department of Pediatrics, King Saud Medical City, Riyadh 11461, Saudi Arabia.
⁴ College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.
⁵ Division of Medical Genetics, Department of Pediatrics, King Saud University Medical City, Riyadh 11461, Saudi Arabia.

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.

Keywords: Saudi Arabia; children; epilepsy; genetics; genotype; mutations; phenotype.

Grants and funding

This work was supported by the National Plan for Science, Technology and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia, Award Number 5-18-03-001-0010.