{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T14:02:01Z","timestamp":1784901721825,"version":"3.55.0"},"reference-count":17,"publisher":"BMJ","issue":"7","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2026,7,13]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>\n                    A child with\n                    <jats:italic>SCN1A<\/jats:italic>\n                    -related \u2018genetic epilepsy with febrile seizures plus\u2019 (GEFS+) presented in infancy with recurrent febrile and afebrile seizures, frequently progressing to generalised tonic-clonic status epilepticus. Despite a severe seizure burden and typical Dravet-like triggers, neurodevelopment remained entirely normal and a familial\n                    <jats:italic>SCN1A<\/jats:italic>\n                    variant supported a diagnosis of GEFS+. The variant (c.5666T&gt;A, p.Met1889Lys) was classified as a variant of uncertain significance fulfilling PM2, PP1 and PP3 criteria and absent from The Genome Aggregation Database (gnomAD) and ClinVar. Identification of the same variant in a neurodevelopmentally normal parent supported inherited GEFS+ rather than Dravet syndrome. After treatment failure with sodium valproate, clobazam and topiramate, low-dose fenfluramine (2.2\u2009mg\/day, 0.15\u2009mg\/kg\/day) achieved seizure freedom maintained for more than 1 year with no adverse effects. This dose is substantially lower than the 0.2\u20130.7\u2009mg\/kg\/day used in Dravet syndrome trials, suggesting GEFS+ may require lower therapeutic thresholds.\n                  <\/jats:p>","DOI":"10.1136\/bcr-2026-273440","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:10:25Z","timestamp":1784898625000},"page":"e273440","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Fenfluramine in refractory\n                    <i>SCN1A<\/i>\n                    -related \u2018genetic epilepsy with febrile seizures plus\u2019"],"prefix":"10.1136","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8094-0574","authenticated-orcid":false,"given":"Tatsuya","family":"Takahashi","sequence":"first","affiliation":[{"name":"Department of Paediatric Neurology, National Center for Child Health and Development, Setagaya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, National Center for Child Health and Development, Setagaya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itaru","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, National Center for Child Health and Development, Setagaya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"2026072406101588000_19.7.e273440.1","doi-asserted-by":"publisher","DOI":"10.1086\/320609"},{"key":"2026072406101588000_19.7.e273440.2","doi-asserted-by":"publisher","DOI":"10.1038\/74159"},{"key":"2026072406101588000_19.7.e273440.3","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/brain\/120.3.479","article-title":"Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes","volume":"120 (Pt 3)","author":"Scheffer","year":"1997","journal-title":"Brain"},{"key":"2026072406101588000_19.7.e273440.4","first-page":"S17","article-title":"SCN1A-related phenotypes: Epilepsy and beyond","volume":"60 Suppl 3","author":"Scheffer","year":"2019","journal-title":"Epilepsia"},{"key":"2026072406101588000_19.7.e273440.5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1528-1167.2011.02994.x","article-title":"The core Dravet syndrome phenotype","volume":"52","author":"Dravet","year":"2011","journal-title":"Epilepsia"},{"key":"2026072406101588000_19.7.e273440.6","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws151"},{"key":"2026072406101588000_19.7.e273440.7","doi-asserted-by":"crossref","first-page":"106441","DOI":"10.1016\/j.neubiorev.2025.106441","article-title":"Early developmental outcome in Dravet syndrome: A scoping review of cognitive, language, behavioural and motor development in the first six years of life","volume":"179","author":"Heineman","year":"2025","journal-title":"Neurosci Biobehav Rev"},{"key":"2026072406101588000_19.7.e273440.8","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1001\/jamaneurol.2019.4113","article-title":"Fenfluramine for treatment-resistant seizures in patients with Dravet syndrome: a randomised, double-blind, placebo-controlled trial","volume":"77","author":"Nabbout","year":"2020","journal-title":"JAMA Neurol"},{"key":"2026072406101588000_19.7.e273440.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32500-0"},{"key":"2026072406101588000_19.7.e273440.10","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1111\/dmcn.14822","article-title":"Fenfluramine as antiseizure medication for epilepsy","volume":"63","author":"Gogou","year":"2021","journal-title":"Dev Med Child Neurol"},{"key":"2026072406101588000_19.7.e273440.11","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2023.1192022","article-title":"Fenfluramine: a plethora of mechanisms?","volume":"14","author":"Sourbron","year":"2023","journal-title":"Front Pharmacol"},{"key":"2026072406101588000_19.7.e273440.12","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2026072406101588000_19.7.e273440.13","first-page":"38","article-title":"Epileptic encephalopathies with SCN1A mutations: phenotype-genotype correlations","volume":"52","author":"Guerrini","year":"2011","journal-title":"Epilepsia"},{"key":"2026072406101588000_19.7.e273440.14","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17241"},{"key":"2026072406101588000_19.7.e273440.15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/j.1528-1167.2011.02997.x","article-title":"The genetics of Dravet syndrome","volume":"52 Suppl 2","author":"Marini","year":"2011","journal-title":"Epilepsia"},{"key":"2026072406101588000_19.7.e273440.16","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/epi4.70187","article-title":"Fenfluramine in SCN1A-related GEFS+: A multicenter observational study on efficacy, EEG improvement, and tolerability","volume":"11","author":"Dell\u2019Isola","year":"2026","journal-title":"Epilepsia Open"},{"key":"2026072406101588000_19.7.e273440.17","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa371"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2026-273440","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:10:26Z","timestamp":1784898626000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2026-273440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":17,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7,24]]},"published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1136\/bcr-2026-273440"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2026-273440","relation":{},"ISSN":["1757-790X"],"issn-type":[{"value":"1757-790X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]}}}