{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:04:58Z","timestamp":1783955098248,"version":"3.55.0"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Gain\u2010of\u2010function (GoF) variants in the\n                      <jats:italic>KCNC1<\/jats:italic>\n                      potassium channel subunit gene (Kv3.1) cause motor\/cognitive delays and hypotonia and have been associated with seizures. Fluoxetine has inhibitory effects on Kv3.1. However, open\u2010label nonrandomized administration is insufficient to guide clinical decision\u2010making in ultrarare conditions. This 40\u2010week randomized, double\u2010blind,\n                      <jats:italic>n<\/jats:italic>\n                      \u2010of\u20101 trial evaluated the safety and effectiveness of fluoxetine for motor development in a 2\u2010year, 10\u2010month\u2010old female child with a GoF\n                      <jats:italic>KCNC1<\/jats:italic>\n                      variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study used an ABA phase design (placebo\u2013fluoxetine\u2013placebo), with randomization and blinding of treatment transition moments. The active treatment, fluoxetine powder, was provided at 2.5\u2009mg (low dose) and subsequently 5\u2009mg (target dose) per day. Motor developmental was measured using the parent\u2010reported Early Motor Questionnaire (EMQ), completed weekly. Secondary outcomes included cognitive and adaptive skills and other parent target symptoms (nystagmus, communication, purposeful hand movements).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment with fluoxetine was associated with a 6.61\u2010point gain on the EMQ (95% credible interval [CrI] = \u2212.53 to 14.78), beyond the effects of time (.52 points\/week, 95% CrI = .28\u2013.91). Treatment was well tolerated; possible withdrawal irritability emerged during the second placebo phase. A higher dose was associated with a larger treatment effect on the EMQ (2.5\u2009mg\u2009=\u20096.81, 95% CrI = \u2212.43 to 14.56; 5\u2009mg\u2009=\u20098.68, 95% CrI = \u22124.29 to 21.76). Secondary outcomes showed significant improvements in purposeful hand movements (\u2212.65, 95% CrI = \u22121.27 to \u2212.003, on a 7\u2010point scale), and there were small increases in adaptive behavior and cognitive skills during the trial. Clinical biomarkers suggested a shift toward increased excitation on electroencephalogram and electroretinogram.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Fluoxetine treatment was possibly associated with increased motor skill development in a young child with\n                      <jats:italic>KCNC1<\/jats:italic>\n                      \u2010related disorder involving a GoF variant. Trials studying developmental endpoints require innovative designs; this study provides a template for treatment assessment in ultrarare genetic neurodevelopmental disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70253","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T08:05:18Z","timestamp":1776499518000},"page":"3644-3656","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An\n                    <i>n<\/i>\n                    \u2010of\u20101 gene\u2010directed drug repurposing trial for an ultrarare genetic condition"],"prefix":"10.1002","volume":"67","author":[{"given":"Vedika","family":"Jha","sequence":"first","affiliation":[{"name":"University of Toronto, Faculty of Medicine  Toronto Ontario 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