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We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.(Leu296Phe) in the gene <jats:italic>KCNA1<\/jats:italic>, encoding the voltage\u2010gated K<jats:sup>+<\/jats:sup> channel subunit K<jats:sub>V<\/jats:sub>1.1. So far, loss\u2010of\u2010function variants in <jats:italic>KCNA1<\/jats:italic> have been associated with episodic ataxia type 1 or epilepsy. Functional studies of the mutated subunit in oocytes revealed a gain\u2010of\u2010function caused by a hyperpolarizing shift of voltage dependence. Leu296Phe channels are sensitive to block by 4\u2010aminopyridine. Clinical use of 4\u2010aminopyridine was associated with reduced seizure burden, enabled simplification of co\u2010medication and prevented rehospitalization.<\/jats:p>","DOI":"10.1002\/acn3.51742","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T06:35:51Z","timestamp":1676529351000},"page":"656-663","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["<i>KCNA1<\/i> gain\u2010of\u2010function epileptic encephalopathy treated with 4\u2010aminopyridine"],"prefix":"10.1002","volume":"10","author":[{"given":"Peter","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research University of Tuebingen  Tuebingen 72076 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle S.","family":"Takacs","sequence":"additional","affiliation":[{"name":"Division of Neurology and Developmental Neuroscience, Epilepsy and Neurophysiology, Department of Pediatrics Texas Children's Hospital, Baylor College of Medicine  Houston Texas USA"},{"name":"Department of Neurology Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike B. 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