{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:26Z","timestamp":1787027846210,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Plan for Science, Technology and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia","award":["5-18-03-001-0010"],"award-info":[{"award-number":["5-18-03-001-0010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/children10081334","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T09:06:44Z","timestamp":1690880804000},"page":"1334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genotype\u2013Phenotype Analysis of Children with Epilepsy Referred for Whole-Exome Sequencing at a Tertiary Care University Hospital"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1436-6727","authenticated-orcid":false,"given":"Fahad A.","family":"Bashiri","sequence":"first","affiliation":[{"name":"Department of Pediatrics, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"},{"name":"Division of Pediatric Neurology, Department of Pediatrics, King Saud University Medical City, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawan","family":"AlSheikh","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, King Saud Medical City, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muddathir H.","family":"Hamad","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, King Saud University Medical City, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamad","family":"Alsheikh","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, King Saud University Medical City, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana Abdullah","family":"Alsheikh","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, King Saud Medical City, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Kentab","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"},{"name":"Division of Pediatric Neurology, Department of Pediatrics, King Saud University Medical City, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najd","family":"AlTheeb","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malak","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"},{"name":"Division of Medical Genetics, Department of Pediatrics, King Saud University Medical City, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/epi.12550","article-title":"ILAE official report: A practical clinical definition of epilepsy","volume":"55","author":"Fisher","year":"2014","journal-title":"Epilepsia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1684\/epd.2015.0736","article-title":"Incidence, prevalence and aetiology of seizures and epilepsy in children","volume":"17","author":"Camfield","year":"2015","journal-title":"Epileptic Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/mrdd.10035","article-title":"The epidemiology of the epilepsies in children","volume":"8","author":"Cowan","year":"2002","journal-title":"Ment. Retard. Dev. Disabil. Res. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/S1059-1311(01)90602-8","article-title":"The prevalence of epilepsy and other seizure disorders in an Arab population: A community-based study","volume":"10","author":"Awada","year":"2001","journal-title":"Seizure"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"463","DOI":"10.2165\/00019053-200826060-00002","article-title":"Cost of epilepsy: A systematic review","volume":"26","author":"Strzelczyk","year":"2008","journal-title":"Pharmacoeconomics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1111\/epi.13084","article-title":"The direct cost of epilepsy in the United States: A systematic review of estimates","volume":"56","author":"Begley","year":"2015","journal-title":"Epilepsia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1111\/epi.13219","article-title":"Population-based comparative analysis of risk of death in children and adolescents with epilepsy and migraine","volume":"56","author":"Selassie","year":"2015","journal-title":"Epilepsia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1016\/S0140-6736(02)08779-2","article-title":"Death in children with epilepsy: A population-based study","volume":"359","author":"Camfield","year":"2002","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.eplepsyres.2011.03.009","article-title":"Incidence and classification of new-onset epilepsy and epilepsy syndromes in children in Olmsted County, Minnesota from 1980 to 2004: A population-based study","volume":"95","author":"Wirrell","year":"2011","journal-title":"Epilepsy Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1684\/epd.2018.0957","article-title":"The 2017 ILAE classification of seizure types and the epilepsies: What do people with epilepsy and their caregivers need to know?","volume":"20","author":"Brodie","year":"2018","journal-title":"Epileptic Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nrneurol.2010.92","article-title":"Genetic evaluation and counseling for epilepsy","volume":"6","author":"Pal","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/epi.13709","article-title":"ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology","volume":"58","author":"Scheffer","year":"2017","journal-title":"Epilepsia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.seizure.2016.11.030","article-title":"Epilepsy-associated genes","volume":"44","author":"Wang","year":"2017","journal-title":"Seizure"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/humu.23943","article-title":"SCN1A variants from bench to bedside-improved clinical prediction from functional characterization","volume":"41","author":"Brunklaus","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1212\/WNL.0b013e3182a43e57","article-title":"Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome","volume":"81","author":"Nakamura","year":"2013","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1111\/epi.13122","article-title":"Obtaining genetic testing in pediatric epilepsy","volume":"56","author":"Ream","year":"2015","journal-title":"Epilepsia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103628","DOI":"10.1016\/j.ejmg.2019.02.001","article-title":"Antiepileptic therapy approaches in KCNQ2 related epilepsy: A systematic review","volume":"63","author":"Kuersten","year":"2020","journal-title":"Eur. J. Med. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.clineuro.2017.12.010","article-title":"Outcome of epilepsy in patients with mitochondrial disorders: Phenotype genotype and magnetic resonance imaging correlations","volume":"164","author":"Bindu","year":"2018","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107003","DOI":"10.1016\/j.yebeh.2020.107003","article-title":"The role of targeted gene panel in pediatric drug-resistant epilepsy","volume":"106","author":"Wu","year":"2020","journal-title":"Epilepsy Behav."},{"key":"ref_20","first-page":"57","article-title":"Clinical characteristics and aetiology of early childhood epilepsy: A single centre experience in Saudi Arabia","volume":"18","author":"Alonazi","year":"2018","journal-title":"Sudan. J. Paediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.seizure.2013.04.002","article-title":"Impact of a family history of epilepsy on the diagnosis of epilepsy in Southern Saudi Arabia","volume":"22","author":"Babtain","year":"2013","journal-title":"Seizure"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.seizure.2019.04.018","article-title":"The landscape of early infantile epileptic encephalopathy in a consanguineous population","volume":"69","author":"Nashabat","year":"2019","journal-title":"Seizure"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1017\/cjn.2015.394","article-title":"Reflex Seizures Triggered by Diaper Change in Dravet Syndrome","volume":"43","author":"Subki","year":"2016","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1179573519849938","DOI":"10.1177\/1179573519849938","article-title":"Biallelic SCN2A Gene Mutation Causing Early Infantile Epileptic Encephalopathy: Case Report and Review","volume":"11","author":"AlSaif","year":"2019","journal-title":"J. Cent. Nerv. Syst. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.braindev.2019.03.009","article-title":"Epilepsy in patients with EAST syndrome caused by mutation in the KCNJ10","volume":"41","author":"Mir","year":"2019","journal-title":"Brain Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"468","DOI":"10.2174\/1871527314666150429111737","article-title":"Array-comparative genomic hybridization analysis of a cohort of Saudi patients with epilepsy","volume":"14","author":"Faheem","year":"2015","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s13258-018-0673-5","article-title":"A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy","volume":"40","author":"Naseer","year":"2018","journal-title":"Genes Genom."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1515\/tnsci-2018-0023","article-title":"Tuberous Sclerosis Complex: Clinical Spectrum and Epilepsy: A Retrospective Chart Review Study","volume":"9","author":"Almobarak","year":"2018","journal-title":"Transl. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/mp.2016.113","article-title":"Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield","volume":"22","author":"Anazi","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"658823","DOI":"10.3389\/fneur.2021.658823","article-title":"Social Cognition in Neurodevelopmental Disorders and Epilepsy","volume":"14","author":"Pastorino","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1055\/s-0039-1691826","article-title":"A Case of Neonatal Epileptic Encephalopathy due to SCN2A Mutation Responsive to a Ketogenic Diet","volume":"7","author":"Bashiri","year":"2018","journal-title":"J. Pediatr. Epilepsy"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.ajhg.2016.10.006","article-title":"Epileptic Encephalopathy Caused by Mutations in the Guanine Nucleotide Exchange Factor DENND5A","volume":"99","author":"Han","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/cge.12297","article-title":"Aminoacylase I deficiency due to ACY1 mRNA exon skipping","volume":"86","author":"Ferri","year":"2014","journal-title":"Clin. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.pediatrneurol.2019.10.009","article-title":"PCDH19-Related Epilepsy Syndrome: A Comprehensive Clinical Review","volume":"105","author":"Samanta","year":"2020","journal-title":"Pediatr. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.eplepsyres.2018.05.004","article-title":"Retrospective genotype-phenotype analysis in a 305 patient cohort referred for testing of a targeted epilepsy panel","volume":"144","author":"Hesse","year":"2018","journal-title":"Epilepsy Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1017\/cjn.2018.341","article-title":"Development of Criteria for Epilepsy Genetic Testing in Ontario, Canada","volume":"46","author":"Jain","year":"2019","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5036","DOI":"10.19082\/5036","article-title":"Epilepsy as a health problem among school children in Turaif, Northern Saudi Arabia, 2017","volume":"9","author":"Alsharif","year":"2017","journal-title":"Electron. Physician"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.seizure.2018.01.002","article-title":"Association between SCN1A gene polymorphisms and drug resistant epilepsy in pediatric patients","volume":"55","author":"Margari","year":"2018","journal-title":"Seizure"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/8\/1334\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:24:00Z","timestamp":1760127840000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/8\/1334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,1]]},"references-count":38,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["children10081334"],"URL":"https:\/\/doi.org\/10.3390\/children10081334","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,1]]}}}