{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:13:21Z","timestamp":1791350001878,"version":"4.3.1"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,4,26]],"date-time":"2013-04-26T00:00:00Z","timestamp":1366934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\"><jats:italic>KCNQ2<\/jats:italic><\/jats:styled-content> mutations have been found in patients with benign familial neonatal seizures, myokymia, or early onset epileptic encephalopathy (<jats:styled-content style=\"fixed-case\">EOEE<\/jats:styled-content>). In this study, we aimed to delineate the clinical spectrum of <jats:styled-content style=\"fixed-case\">EOEE<\/jats:styled-content> associated with <jats:styled-content style=\"fixed-case\"><jats:italic>KCNQ2<\/jats:italic><\/jats:styled-content> mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 239 patients with <jats:styled-content style=\"fixed-case\">EOEE<\/jats:styled-content>, including 51 cases with Ohtahara syndrome and 104 cases with West syndrome, were analyzed by high\u2010resolution melting (<jats:styled-content style=\"fixed-case\">HRM<\/jats:styled-content>) analysis or whole\u2010exome sequencing. Detailed clinical information including electroencephalography (<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>) and brain magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>) were collected from patients with <jats:styled-content style=\"fixed-case\"><jats:italic>KCNQ2<\/jats:italic><\/jats:styled-content> mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Findings<\/jats:title><jats:p>A total of nine de novo and one inherited mutations were identified (two mutations occurred recurrently). The initial seizures, which were mainly tonic seizures, occurred in the early neonatal period in all 12 patients. A suppression\u2010burst pattern on <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content> was found in most. Only three patients showed hypsarrhythmia on <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>; eight patients became seizure free when treated with carbamazepine, zonisamide, phenytoin, topiramate, or valproic acid. Although the seizures were relatively well controlled, moderate\u2010to\u2010profound intellectual disability was found in all except one patient who died at 3\u00a0months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>De novo <jats:styled-content style=\"fixed-case\"><jats:italic>KCNQ2<\/jats:italic><\/jats:styled-content> mutations are involved in <jats:styled-content style=\"fixed-case\">EOEE<\/jats:styled-content>, most of which cases were diagnosed as Ohtahara syndrome. These cases showed distinct features with early neonatal onset, tonic seizures, a suppression\u2010burst <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content> pattern, infrequent evolution to West syndrome, and good response to sodium channel blockers, but poor developmental prognosis. Genetic testing for <jats:styled-content style=\"fixed-case\"><jats:italic>KCNQ2<\/jats:italic><\/jats:styled-content> should be considered for patients with <jats:styled-content style=\"fixed-case\">EOEE<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12200","type":"journal-article","created":{"date-parts":[[2013,4,26]],"date-time":"2013-04-26T13:51:43Z","timestamp":1366984303000},"page":"1282-1287","source":"Crossref","is-referenced-by-count":213,"title":["Clinical spectrum of early onset epileptic encephalopathies caused by <scp><i>KCNQ2<\/i><\/scp> mutation"],"prefix":"10.1111","volume":"54","author":[{"given":"Mitsuhiro","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Pediatrics Yamagata University Faculty of Medicine Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Yamagata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Jichi Medical University Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Kubota","sequence":"additional","affiliation":[{"name":"Division of Neurology National Center for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Morinomiya Hospital Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumimasa","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Division of Child Neurology Kanagawa Children's Medical Center Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanari","family":"FujII","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Showa University Faculty of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Sugai","sequence":"additional","affiliation":[{"name":"Department of Child Neurology National Center Hospital National Center of Neurology and Psychiatry Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tokyo Women's Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tami","family":"Uster","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Prenatal Diagnosis and Medical Genetics Program Mount Sinai Hospital University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chitayat","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Prenatal Diagnosis and Medical Genetics Program Mount Sinai Hospital University of Toronto Toronto Ontario Canada"},{"name":"Division of Clinical and Metabolic Genetics Department of Pediatrics The Hospital for Sick Children University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelly","family":"Weiss","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Pediatrics The Hospital for Sick Children University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Kashii","sequence":"additional","affiliation":[{"name":"Division of Neurology National Center for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Kusano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Jichi Medical University Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Jichi Medical University Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University Faculty of Medicine Yamagata Japan"},{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Oyazato","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Maeno","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyomi","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Kodera","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuko","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Tsurusaki","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayoko","family":"Saito","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Tokyo Women's Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Hayasaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University Faculty of Medicine Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomichi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotomo","family":"Saitsu","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,4,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5349.403"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000132979.08394.6D"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/320609"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(03)00037-8"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f6bc97"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/375538"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/518903"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl019"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21554"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/427564"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-8994(01)00365-4"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01629-5"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.7.1355"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.150"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23620"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03548.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2005.05.009"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0198-25"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg286"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2006.10.010"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng862"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.06.064"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22644"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.12200","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.12200","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T02:06:01Z","timestamp":1696298761000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.12200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,26]]},"references-count":25,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["10.1111\/epi.12200"],"URL":"https:\/\/doi.org\/10.1111\/epi.12200","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,26]]}}}