{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:47:01Z","timestamp":1791424021160,"version":"4.3.3"},"reference-count":40,"publisher":"Georg Thieme Verlag KG","issue":"05","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background\u2003Autosomal dominant mutations of the KCNQ2 gene can cause two epileptic disorders: benign familial neonatal seizures (BFNS) and developmental epileptic encephalopathy (DEE). This systematic review aims to identify the best reported therapy for these patients, relating to phenotype, neurodevelopmental outcome, and an eventual correlation between phenotype and genotype.<\/jats:p><jats:p>\n          Methods\u2003We searched on PubMed using the search terms \u201cKCNQ2\u201d AND \u201ctherapy\u201d and \u201cKCNQ2\u201d AND \u201ctreatment\u201d; we found 304 articles. Of these, 29 met our criteria. We collected the data from 194 patients. All 29 articles were retrospective studies.<\/jats:p><jats:p>\n          Results\u2003In all, 104 patients were classified as DEE and 90 as BFNS. After treatment began, 95% of BFNS patients became seizure free, whereas the seizures stopped only in 73% of those with DEE. Phenobarbital and sodium channel blockers were the most used treatment in BFNS. Most of the DEE patients (95%) needed polytherapy for seizure control and even that did not prevent subsequent developmental impairment (77%).<\/jats:p><jats:p>Missense mutations were discovered in 96% of DEE patients; these were less common in BFNS (50%), followed by large deletion (16%), truncation (16%), splice donor site (10%), and frameshift (7%).<\/jats:p><jats:p>\n          Conclusion\u2003Phenobarbital or carbamazepine appears to be the most effective antiseizure medication for children with a \u201cbenign\u201d variant. On the contrary, polytherapy is often needed for DEE patients, even if it does not seem to improve neurological outcomes. In DEE patients, most mutations were located in S4 and S6 helix, which could serve as a potential target for the development of more specific treatment in the future.<\/jats:p>","DOI":"10.1055\/a-2060-4576","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T23:52:41Z","timestamp":1679529161000},"page":"297-307","source":"Crossref","is-referenced-by-count":15,"title":["KCNQ2-Related Epilepsy: Genotype\u2013Phenotype Relationship with Tailored Antiseizure Medication (ASM)\u2014A Systematic Review"],"prefix":"10.1055","volume":"54","author":[{"given":"Raffaele","family":"Falsaperla","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit and Neonatal Accompaniment Unit, Azienda Ospedaliero-Universitaria Policlinico \u201cRodolico-San Marco\u201d, San Marco Hospital, University of Catania, Catania, Italy"},{"name":"Unit of Clinical Paediatrics, Azienda Ospedaliero-Universitaria Policlinico, \u201cRodolico-San Marco\u201d, San Marco Hospital, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Criscione","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit and Neonatal Accompaniment Unit, Azienda Ospedaliero-Universitaria Policlinico \u201cRodolico-San Marco\u201d, Postgraduate Training Program in Pediatrics, University of Catania, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Cimino","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit and Neonatal Accompaniment Unit, Azienda Ospedaliero-Universitaria Policlinico \u201cRodolico-San Marco\u201d, San Marco Hospital, University of Catania, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Pisani","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit, Human Neuroscience Department, Sapienza University of Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martino","family":"Ruggieri","sequence":"additional","affiliation":[{"name":"Unit of Clinical Pediatrics, Department of Clinical and Experimental Medicine, University of Catania, AOU \u201cPoliclinico\u201d, PO \u201cG. Rodolico\u201d, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"issue":"11","key":"ref1","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1212\/01.WNL.0000145629.94338.89","article-title":"De novo KCNQ2 mutations in patients with benign neonatal seizures","volume":"63","author":"L R Claes","year":"2004","journal-title":"Neurology"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0920-1211(03)00037-8","article-title":"Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2","volume":"54","author":"K Dedek","year":"2003","journal-title":"Epilepsy Res"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1212\/01.WNL.0000132979.08394.6D","article-title":"A novel mutation in KCNQ2 associated with BFNC, drug resistant 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myoclonus is a prominent clinical feature of KCNQ2 gain-of-function variants R201C and R201H","volume":"58","author":"S B Mulkey","year":"2017","journal-title":"Epilepsia"},{"issue":"04","key":"ref33","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1159\/000478651","article-title":"A Distinctive Ictal Amplitude-Integrated Electroencephalography Pattern in Newborns with Neonatal Epilepsy Associated with KCNQ2 Mutations","volume":"112","author":"A Vilan","year":"2017","journal-title":"Neonatology"},{"issue":"01","key":"ref34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.braindev.2017.06.008","article-title":"KCNQ2 encephalopathy: A case due to a de novo deletion","volume":"40","author":"C Spagnoli","year":"2018","journal-title":"Brain Dev"},{"issue":"03","key":"ref35","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1684\/epd.2017.0927","article-title":"Pointed rhythmic theta waves: a unique EEG pattern in KCNQ2-related neonatal epileptic encephalopathy","volume":"19","author":"S G Buttle","year":"2017","journal-title":"Epileptic Disord"},{"issue":"02","key":"ref36","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.braindev.2020.08.015","article-title":"Clinical characteristics of KCNQ2 encephalopathy","volume":"43","author":"H J Kim","year":"2021","journal-title":"Brain Dev"},{"key":"ref37","first-page":"1993","volume-title":"KCNQ2-Related Disorders. 2010 Apr 27 [updated 2022 May 19]","author":"F Miceli"},{"issue":"12","key":"ref38","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1111\/epi.13596","article-title":"Rapid and safe response to low-dose carbamazepine in neonatal epilepsy","volume":"57","author":"T T Sands","year":"2016","journal-title":"Epilepsia"},{"issue":"45","key":"ref39","doi-asserted-by":"crossref","first-page":"18577","DOI":"10.1073\/pnas.1209142109","article-title":"Modulation of voltage-gated K+ channels by the sodium channel \u03b21 subunit","volume":"109","author":"H M 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Dermatol"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2060-4576.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T23:16:03Z","timestamp":1695078963000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2060-4576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,22]]},"references-count":40,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2023,9,18]]},"published-print":{"date-parts":[[2023,10]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2060-4576","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,3,22]]},"published":{"date-parts":[[2023,3,22]]}}}