{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T12:42:43Z","timestamp":1788093763451,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T00:00:00Z","timestamp":1485820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001454","name":"American Epilepsy Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001454","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001605","name":"Epilepsy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001605","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007856","name":"Baylor College of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008519","name":"University of Arkansas for Medical Sciences","doi-asserted-by":"publisher","award":["P30 GM110702"],"award-info":[{"award-number":["P30 GM110702"]}],"id":[{"id":"10.13039\/100008519","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GGP15113"],"award-info":[{"award-number":["GGP15113"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS49119"],"award-info":[{"award-number":["R01 NS49119"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To analyze whether\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">KCNQ<\/jats:styled-content>\n                        2\n                      <\/jats:italic>\n                      R201C and R201H variants, which show atypical gain\u2010of\u2010function electrophysiologic properties in vitro\n                      <jats:italic>,<\/jats:italic>\n                      have a distinct clinical presentation and outcome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Ten children with heterozygous, de novo\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">KCNQ<\/jats:styled-content>\n                        2\n                      <\/jats:italic>\n                      R201C or R201H variants were identified worldwide, using an institutional review board (\n                      <jats:styled-content style=\"fixed-case\">IRB<\/jats:styled-content>\n                      )\u2013approved\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">KCNQ<\/jats:styled-content>\n                        2\n                      <\/jats:italic>\n                      patient registry and database. We reviewed medical records and, where possible, interviewed parents and treating physicians using a structured, detailed phenotype inventory focusing on the neonatal presentation and subsequent course.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nine patients had encephalopathy from birth and presented with prominent startle\u2010like myoclonus, which could be triggered by sound or touch. In seven patients, electroencephalography (\n                      <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>\n                      ) was performed in the neonatal period and showed a burst\u2010suppression pattern. However, myoclonus did not have an\n                      <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>\n                      correlate. In many patients the paroxysmal movements were misdiagnosed as seizures. Seven patients developed epileptic spasms in infancy. In all patients,\n                      <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>\n                      showed a slow background and multifocal epileptiform discharges later in life. Other prominent features included respiratory dysfunction (perinatal respiratory failure and\/or chronic hypoventilation), hypomyelination, reduced brain volume, and profound developmental delay. One patient had a later onset, and sequencing indicated that a low abundance (~20%) R201C variant had arisen by postzygotic mosaicism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Heterozygous\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">KCNQ<\/jats:styled-content>\n                        2\n                      <\/jats:italic>\n                      R201C and R201H gain\u2010of\u2010function variants present with profound neonatal encephalopathy in the absence of neonatal seizures. Neonates present with nonepileptic myoclonus that is often misdiagnosed and treated as seizures. Prognosis is poor. This clinical presentation is distinct from the phenotype associated with loss\u2010of\u2010function variants, supporting the value of in vitro functional screening. These findings suggest that gain\u2010of\u2010function and loss\u2010of\u2010function variants need different targeted therapeutic approaches.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.13676","type":"journal-article","created":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T06:55:13Z","timestamp":1485845713000},"page":"436-445","source":"Crossref","is-referenced-by-count":110,"title":["Neonatal nonepileptic myoclonus is a prominent clinical feature of\n                    <i>\n                      <scp>KCNQ<\/scp>\n                      2\n                    <\/i>\n                    gain\u2010of\u2010function variants R201C and R201H"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8084-526X","authenticated-orcid":false,"given":"Sarah B.","family":"Mulkey","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Arkansas for Medical Sciences Little Rock Arkansas U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruria","family":"Ben\u2010Zeev","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Sackler School of Medicine Tel Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost","family":"Nicolai","sequence":"additional","affiliation":[{"name":"Department of Neurology Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Arkansas for Medical Sciences Little Rock Arkansas U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Gr\u00f8nborg","sequence":"additional","affiliation":[{"name":"Center for Rare Diseases Department of Clinical Genetics University Hospital Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010hui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Neurobiology Duke University Medical Center Durham North Carolina U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishtha","family":"Joshi","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Neuroscience, and Molecular and Human Genetics Baylor College of Medicine Houston Texas U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Kelly","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Neurobiology Duke University Medical Center Durham North Carolina U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David. 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