{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T05:14:05Z","timestamp":1763183645429,"version":"3.45.0"},"reference-count":21,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"ISCIII","doi-asserted-by":"publisher","award":["FIS18\/01433 (PI-3569)"],"award-info":[{"award-number":["FIS18\/01433 (PI-3569)"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"FIBHULP","award":["PI-2734"],"award-info":[{"award-number":["PI-2734"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Wolf\u2013Hirschhorn syndrome (WHS) is a rare contiguous gene deletion disorder associated with a high incidence of early-onset epilepsy. Despite the clinical relevance of seizures in this population, few large-scale studies have provided detailed data on epilepsy phenotypes and treatment outcomes. Methods: We analyzed a cohort of 140 individuals with WHS from Spain and Latin America. Using validated caregiver-reported questionnaires, we collected detailed information on seizure types, antiseizure medications (ASM) use, and associated comorbidities. Statistical comparisons were made to identify correlations between epilepsy severity, deletion size, and functional outcomes. Results: Epilepsy was observed in 92% of patients, typically beginning before 12 months of age. Multiple seizure types were common, particularly generalized tonic\u2013clonic and atypical absence seizures. Status epilepticus occurred in 58% of cases, with a high proportion requiring multiple ASMs. Valproic acid and levetiracetam were the most commonly used treatments. Patients with more severe epilepsy tended to have larger deletions (&gt;9 Mb) and poorer developmental outcomes. ASM discontinuation was significantly associated with older age at evaluation, supporting improved seizure control over time. Conclusions: Epilepsy in WHS is frequent, often severe in early childhood, and associated with neurodevelopmental impairment and increased treatment burden. While some patients show improvement with age, early aggressive management using appropriate ASMs may be critical to improve neurological prognosis. Advances in diagnosis, early intervention, and targeted therapies offer hope for improved long-term outcomes in this vulnerable population.<\/jats:p>","DOI":"10.3390\/jcm14228044","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T16:46:22Z","timestamp":1763138782000},"page":"8044","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epilepsy in Wolf\u2013Hirschhorn Syndrome: Clinical Insights from a Pediatric Cohort and a Review of the Literature"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6500-9511","authenticated-orcid":false,"given":"Raquel","family":"Blanco-Lago","sequence":"first","affiliation":[{"name":"Neuropediatrics Service, Universitary Hospital Central de Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4074-6870","authenticated-orcid":false,"given":"Ignacio","family":"M\u00e1laga","sequence":"additional","affiliation":[{"name":"Neuropediatrics Service, Universitary Hospital Central de Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5308-2316","authenticated-orcid":false,"given":"Jair Antonio","family":"Tenorio-Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Medical and Molecular Genetics Institute (INGEMM)-IdiPAZ, Universitary Hospital of La Paz, 28046 Madrid, Spain"},{"name":"CIBERER\u2014Biomedical Research Network Centre in Rare Diseases, National Health Institute Carlos III (ISCIII), 28046 Madrid, Spain"},{"name":"ITHACA-European Reference Network-Hospital la Paz, 28046 Madrid, Spain"},{"name":"Facultad HM de Ciencias de la Salud, Universidad Camilo Jos\u00e9 Cela, 28015 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelly","family":"\u00c1lvarez-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Neuropediatrics Service, Universitary Hospital Central de Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6324-4825","authenticated-orcid":false,"given":"Pablo","family":"Lapunzina","sequence":"additional","affiliation":[{"name":"Medical and Molecular Genetics Institute (INGEMM)-IdiPAZ, Universitary Hospital of La Paz, 28046 Madrid, Spain"},{"name":"CIBERER\u2014Biomedical Research Network Centre in Rare Diseases, National Health Institute Carlos III (ISCIII), 28046 Madrid, Spain"},{"name":"ITHACA-European Reference Network-Hospital la Paz, 28046 Madrid, Spain"},{"name":"Facultad HM de Ciencias de la Salud, Universidad Camilo Jos\u00e9 Cela, 28015 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-2659","authenticated-orcid":false,"given":"Juli\u00e1n","family":"Nevado","sequence":"additional","affiliation":[{"name":"Medical and Molecular Genetics Institute (INGEMM)-IdiPAZ, Universitary Hospital of La Paz, 28046 Madrid, Spain"},{"name":"CIBERER\u2014Biomedical Research Network Centre in Rare Diseases, National Health Institute Carlos III (ISCIII), 28046 Madrid, Spain"},{"name":"ITHACA-European Reference Network-Hospital la Paz, 28046 Madrid, Spain"},{"name":"Facultad HM de Ciencias de la Salud, Universidad Camilo Jos\u00e9 Cela, 28015 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0065-3101(23)00074-9","article-title":"Wolf-Hirschhorn (4p-) syndrome","volume":"48","author":"Battaglia","year":"2001","journal-title":"Adv. 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