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While the association of epilepsy and intellectual disability (ID) with variants affecting function in genes encoding potassium channels is well known, GOF missense variants in K<jats:sup>+<\/jats:sup> channel encoding genes in individuals with syndromic developmental disorders have only recently been recognized. These syndromic phenotypes include Zimmermann\u2013Laband and Temple\u2013Baraitser syndromes, caused by dominant variants in <jats:italic>KCNH1<\/jats:italic>, FHEIG syndrome due to dominant variants in <jats:italic>KCNK4<\/jats:italic>, and the clinical picture\u00a0associated with dominant variants in <jats:italic>KCNN3<\/jats:italic>. Here we review the presentation of these individuals, including five newly reported with variants in <jats:italic>KCNH1<\/jats:italic> and three additional individuals with <jats:italic>KCNN3<\/jats:italic> variants, all variants likely affecting function. There is notable overlap in the phenotypic findings of these syndromes associated with dominant <jats:italic>KCNN3<\/jats:italic>, <jats:italic>KCNH1<\/jats:italic>, and <jats:italic>KCNK4<\/jats:italic> variants, sharing developmental delay and\/or ID, coarse facial features, gingival enlargement, distal digital hypoplasia, and hypertrichosis. We suggest to combine the phenotypes and define a new subgroup of potassium channelopathies caused by increased K<jats:sup>+<\/jats:sup> conductance, referred to as syndromic neurodevelopmental K<jats:sup>+<\/jats:sup> channelopathies due to dominant variants in <jats:italic>KCNH1<\/jats:italic>, <jats:italic>KCNK4<\/jats:italic>, or <jats:italic>KCNN3<\/jats:italic>.<\/jats:p>","DOI":"10.1038\/s41431-021-00818-9","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T04:57:47Z","timestamp":1613797067000},"page":"1384-1395","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3\u2014a subgroup of K+ channelopathies"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8200-1733","authenticated-orcid":false,"given":"Karen W.","family":"Gripp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah F.","family":"Smithson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid J.","family":"Scurr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0915-5028","authenticated-orcid":false,"given":"Julia","family":"Baptista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anirban","family":"Majumdar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germaine","family":"Pierre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay B.","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid M.","family":"Wentzensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"McLaughlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1105-0455","authenticated-orcid":false,"given":"Lisette","family":"Leeuwen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen E. 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