{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:33:59Z","timestamp":1789450439527,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epileptic Disorders"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Variants in the <jats:italic>ATP1A2<\/jats:italic> gene exhibit a wide clinical spectrum, ranging from familial hemiplegic migraine to childhood epilepsies and early infantile developmental epileptic encephalopathy (EIDEE) with movement disorders. This study aims to describe the epileptology of three unpublished cases and summarize epilepsy features of the other 17 published cases with <jats:italic>ATP1A2<\/jats:italic> variants and EIDEE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Medical records of three novel patients with pathogenic <jats:italic>ATP1A2<\/jats:italic> variants were retrospectively reviewed. Additionally, the PUBMED, EMBASE, and Cochrane databases were searched until December 2023 for articles on EIDEE with ATP1A2 variants, without language or publication year restrictions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three female patients, aged 6 months\u201310\u2009years, were investigated. Epilepsy onset occurred between 5\u2009days and 2\u2009years, accompanied by severe developmental delay, intellectual disability, drug\u2010resistant epilepsy, severe movement disorder, and recurrent status epilepticus. All individuals had pathogenic variants of the <jats:italic>ATP1A2<\/jats:italic> gene (<jats:italic>ATP1A2<\/jats:italic> c.720_721del (p.Ile240MetfsTer9), <jats:italic>ATP1A2c.3022C\u2009&gt;\u2009T (p.Arg1008Trp)<\/jats:italic>, <jats:italic>ATP1A2 c.1096G\u2009&gt;\u2009T (p.Gly366Cys)<\/jats:italic>, according to ACMG criteria. Memantine was p) rescribed to three patients, one with a reduction in ictal frequency, one with improvement in gait pattern, coordination, and attention span, and another one in alertness without significant side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study reinforces the association between <jats:italic>ATP1A2<\/jats:italic> variants and a severe phenotype. All patients had de novo variants, focal motor seizures with impaired awareness as the primary type of seizure; of the 11 EEGs recorded, 10 presented a slow background rhythm, 7 multifocal interictal epileptiform discharges (IED), predominantly temporal IEDs, followed by frontal IED, as well as ten ictal recordings, which showed ictal onset from the same regions mentioned above. Treatment with antiseizure medication was generally ineffective, but memantine showed moderate improvement. Prospective studies are needed to enlarge the phenotype and assess the efficacy of NMDA receptor antagonist therapies in reducing seizure frequency and improving quality of life.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epd2.20220","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T14:14:57Z","timestamp":1711030497000},"page":"332-340","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<i>ATP1A2<\/i>\u2010related epileptic encephalopathy and movement disorder: Clinical features of three novel patients"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2446-7890","authenticated-orcid":false,"given":"Natalia Mart\u00ednez","family":"C\u00f3rdoba","sequence":"first","affiliation":[{"name":"Universidad Militar Nueva Granada  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1416-3201","authenticated-orcid":false,"given":"Isabella","family":"Lince\u2010Rivera","sequence":"additional","affiliation":[{"name":"Universidad Militar Nueva Granada  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2697-2380","authenticated-orcid":false,"given":"Jorge Luis Ram\u00f3n","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Movement Disorders Specialist Instituto Roosevelt  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5309-2514","authenticated-orcid":false,"given":"Guido","family":"Rubboli","sequence":"additional","affiliation":[{"name":"Danish Epilepsy Center, Member of ERN EpiCARE  Dianalund Denmark"},{"name":"Institute of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3432-1932","authenticated-orcid":false,"given":"Sebasti\u00e1n Ortiz","family":"De\u00a0la\u00a0Rosa","sequence":"additional","affiliation":[{"name":"Instituto Roosevelt  Bogot\u00e1 Colombia"},{"name":"Department of Epilepsy Genetics and Personalized Medicine Danish Epilepsy Centre  Dianalund Denmark"},{"name":"Department of Regional Health Research, Faculty of Health Sciences University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17241"},{"key":"e_1_2_11_3_1","first-page":"1","article-title":"GABAA receptors in epilepsy: elucidating phenotypic divergence through functional analysis of genetic variants","author":"Absalom NL","year":"2023","journal-title":"J Neurochem 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