{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T03:33:28Z","timestamp":1778211208942,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PSG297"],"award-info":[{"award-number":["PSG297"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PRG471"],"award-info":[{"award-number":["PRG471"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PRG2040"],"award-info":[{"award-number":["PRG2040"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PSG774"],"award-info":[{"award-number":["PSG774"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["UM1HG008900"],"award-info":[{"award-number":["UM1HG008900"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"National Heart, Lung, and Blood Institute under the Trans-Omics for Precision Medicine (TOPMed) program and the National Eye Institute","doi-asserted-by":"publisher","award":["K23HD102589"],"award-info":[{"award-number":["K23HD102589"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Reports"],"abstract":"<jats:p>Background\/Objectives: Drug-resistant epilepsy (DRE) is a significant health problem leading to cognitive impairment and reduced quality of life. This study aimed to investigate the incidence and etiology of DRE in children in Estonia. Methods: A retrospective, population-based study of childhood DRE was conducted in Estonia from 1 January 2013, to 31 December 2017. All cases were identified through the only two pediatric neurology departments in the country, both located at tertiary care hospitals (Tartu University Hospital and Tallinn Children\u2019s Hospital), ensuring complete nationwide coverage. Epidemiological, magnetic resonance imaging (MRI), and genetic data (chromosomal microarray, single-gene tests, gene panels, and exome\/genome sequencing) were collected. Results: The incidence rate of childhood epilepsy was 84.1 per 100,000. DRE developed in 10% of children with new-onset epilepsy, corresponding to an incidence rate of 8.5 per 100,000. Etiologically relevant MRI abnormalities were identified in 43% of patients with DRE, most commonly congenital brain malformations (19%). Pathogenic single-gene sequence variants were detected in 25 of 110 patients (23%), copy number variants in four patients (4%), and chromosomal aberrations in one patient (1%). Novel candidate disease genes of uncertain pathogenicity were identified in four patients (4%). The most frequent etiology of DRE was structural (29%), followed by genetic (19%), with combined etiologies (13%) also contributing significantly. Conclusions: Our study is the first epidemiological study of DRE in children in Estonia and the Baltic region. The relatively low incidence observed may reflect the comprehensive national ascertainment and centralized management of pediatric epilepsy in tertiary care centers.<\/jats:p>","DOI":"10.3390\/pediatric18010008","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:13:18Z","timestamp":1767697998000},"page":"8","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nationwide Study of Pediatric Drug-Resistant Epilepsy in Estonia: Lower Incidence and Insights into Etiology"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6020-5492","authenticated-orcid":false,"given":"Stella","family":"Lilles","sequence":"first","affiliation":[{"name":"Children\u2019s Clinic, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia"},{"name":"Children\u2019s Clinic, Tartu University Hospital, European Reference Network EpiCARE, 50406 Tartu, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klari","family":"Heidmets","sequence":"additional","affiliation":[{"name":"Children\u2019s Clinic, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia"},{"name":"Children\u2019s Clinic, Tartu University Hospital, European Reference Network EpiCARE, 50406 Tartu, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7084-0238","authenticated-orcid":false,"given":"Kaisa Teele","family":"Oja","sequence":"additional","affiliation":[{"name":"Genetics and Personalized Medicine Clinic, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia"},{"name":"Genetics and Personalized Medicine Clinic, Tartu University Hospital, 50406 Tartu, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karit","family":"Reinson","sequence":"additional","affiliation":[{"name":"Genetics and Personalized Medicine Clinic, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia"},{"name":"Genetics and Personalized Medicine Clinic, Tartu University Hospital, 50406 Tartu, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5727-6759","authenticated-orcid":false,"given":"Laura","family":"Roht","sequence":"additional","affiliation":[{"name":"Genetics and Personalized Medicine Clinic, Tartu University Hospital, 50406 Tartu, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5435-0781","authenticated-orcid":false,"given":"Sander","family":"Pajusalu","sequence":"additional","affiliation":[{"name":"Genetics and Personalized Medicine Clinic, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia"},{"name":"Genetics and Personalized Medicine Clinic, Tartu University Hospital, 50406 Tartu, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8162-5031","authenticated-orcid":false,"given":"Monica H","family":"Wojcik","sequence":"additional","affiliation":[{"name":"Divisions of Newborn Medicine and Genetics and Genomics, Department of Pediatrics, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Department of Pediatrics, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4594-6364","authenticated-orcid":false,"given":"Katrin","family":"\u00d5unap","sequence":"additional","affiliation":[{"name":"Genetics and Personalized Medicine Clinic, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia"},{"name":"Genetics and Personalized Medicine Clinic, Tartu University Hospital, 50406 Tartu, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inga","family":"Talvik","sequence":"additional","affiliation":[{"name":"Children\u2019s Clinic, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia"},{"name":"Tallinn Children\u2019s Hospital, European Reference Network EpiCARE, 13419 Tallinn, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/j.0013-9580.2005.66104.x","article-title":"Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy 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