{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:05:05Z","timestamp":1791266705375,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR3004"],"award-info":[{"award-number":["FOR3004"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1315"],"award-info":[{"award-number":["SFB1315"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006188","name":"Einstein Stiftung Berlin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Developmental and epileptic encephalopathy with continuous spike\u2010and\u2010wave activation in sleep (CSWS) or DEE\u2010SWAS is an age\u2010dependent disease, often accompanied by a decline in cognitive abilities. Early successful treatment of CSWS is associated with a better cognitive outcome. We retrospectively analyzed the clinical, electrophysiological, radiological, and genetic data of children with DEE\u2010SWAS associated with melastatin\u2010related transient receptor type 3 gene (<jats:italic>TRPM3<\/jats:italic>) missense variants. We report two unrelated children with pharmacoresistant DEE\u2010SWAS and developmental delay\/regression and different heterozygous de novo missense variants in the <jats:italic>TRPM3<\/jats:italic> gene (NM_001366145.2; c.3397\u2009T\u2009&gt;\u2009C\/p.Ser1133Pro, c.2004G\u2009&gt;\u2009A\/p.Val1002Met). The variant p.Val1002Met (previously known as p.Val990Met or p.Val837Met) and p.Ser1133Pro were recently shown to result in a gain\u2010of\u2010function effect. Based on this finding, previous drug resistance, and the experimentally demonstrated inhibitory effect of primidone on TRPM3, we initiated an individualized therapy with this drug. In both children, developmental regression was stopped, psychomotor development improved, and CSWS was no longer detectable. To our knowledge, this is the first report of a treatment with primidone in <jats:italic>TRPM3<\/jats:italic>\u2010associated CSWS. Our results highlight the importance of early genetic diagnosis in patients with epilepsy and the possibility of precision medicine, which should be considered in the future in individuals with a <jats:italic>TRPM3<\/jats:italic>\u2010linked DEE\u2010SWAS.<\/jats:p>","DOI":"10.1111\/epi.17586","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T13:03:36Z","timestamp":1678971816000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Primidone improves symptoms in <i>TRPM3<\/i>\u2010linked developmental and epileptic encephalopathy with spike\u2010and\u2010wave activation in sleep"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4622-8695","authenticated-orcid":false,"given":"Lena\u2010Luise","family":"Becker","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Center for Chronically Sick Children Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Institute for Cell Biology and Neurobiology Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Horn","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Human Genetics Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Boschann","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Human Genetics Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3897-8998","authenticated-orcid":false,"given":"Evelien","family":"Van\u00a0Hoeymissen","sequence":"additional","affiliation":[{"name":"Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine University of Leuven  Leuven Belgium"},{"name":"VIB Center for Brain and Disease Research  Leuven Belgium"},{"name":"Laboratory of Endometrium, Endometriosis, and Reproductive Medicine, Department of Development and Regeneration University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-5821","authenticated-orcid":false,"given":"Thomas","family":"Voets","sequence":"additional","affiliation":[{"name":"Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine University of Leuven  Leuven Belgium"},{"name":"VIB Center for Brain and Disease Research  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2502-0409","authenticated-orcid":false,"given":"Joris","family":"Vriens","sequence":"additional","affiliation":[{"name":"Laboratory of Endometrium, Endometriosis, and Reproductive Medicine, Department of Development and Regeneration University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5113-2199","authenticated-orcid":false,"given":"Christine","family":"Prager","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Center for Chronically Sick Children Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9454-206X","authenticated-orcid":false,"given":"Angela M.","family":"Kaindl","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Center for Chronically Sick Children Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Institute for Cell Biology and Neurobiology Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2019.1060"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2019.1063"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.4103\/jpn.JPN_137_20"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNP.0000000000000235"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.607965"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2012.0482"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-019-0462-x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.57190"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.02.051"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1801"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000846"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55634"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.81032"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-021-02719-8"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62673"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2020.103942"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2021.104320"},{"key":"e_1_2_9_19_1","volume-title":"Primidone","author":"Lenkapothula 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