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

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.

A journey from being preterm to pediatric neurology.

This article highlights the story of two pediatric neurology residents (identical twin sisters Rana and Rawan) who work at the Division of Pediatric Neurology, Department of Pediatrics, College of Medicine and King Khalid University Hospital (KKUH), King Saud University, Riyadh, Saudi Arabia. They were born in October 1990 in the same hospital (KKUH), following preterm delivery at 33 weeks. Their birth weight was 2,000 and 1,900 g, respectively. They were admitted to the Neonatal Intensive Care Unit (NICU) at KKUH for 2 weeks. Enduring prolonged struggles due to respiratory related conditions and frequent visits to the Emergency Room during their childhood, they excelled in school graduating with high honors throughout elementary, intermediate, and secondary schools. They joined the College of Medicine, KKUH and graduated with the highest distinction (summa cum laude), and were chosen to join the Saudi Board of Pediatric Neurology Residency Program at KKUH. Their story was revealed, while they were doing a round at the same NICU, where they were once cared for 28 years earlier.