{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:44:44Z","timestamp":1789155884063,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T00:00:00Z","timestamp":1584057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1\u2010related epilepsy and explored genotype\u2010phenotype correlations associated with frequently encountered variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A cross\u2010sectional analysis of children harboring pathogenic or likely pathogenic <jats:italic>KCNT1<\/jats:italic> variants was completed. Children with one of the two more common recurrent <jats:italic>KCNT1<\/jats:italic> variants were compared with the rest of the cohort for the presence of particular characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010seven children (15 males, mean age = 40.8\u00a0months) were included. Seizure onset ranged from 1\u00a0day to 6\u00a0months, and half (48.1%) exhibited developmental plateauing upon onset. Two\u2010thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent <jats:italic>KCNT1<\/jats:italic> variants were c.2800G&gt;A; p.Ala934Thr (n\u00a0=\u00a05) and c.862G&gt;A; p.Gly288Ser (n\u00a0=\u00a04). De novo variants were found in 96% of tested parents (23\/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray\u2010white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4\/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (&gt;50% seizure reduction) or some improvement (25%\u201050% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, &gt;500 seizures\/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence\u2010based practice is still unavailable.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16480","type":"journal-article","created":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T14:49:13Z","timestamp":1584110953000},"page":"679-692","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["KCNT1\u2010related epilepsy: An international multicenter cohort of 27 pediatric cases"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7897-4700","authenticated-orcid":false,"given":"Felippe","family":"Borlot","sequence":"first","affiliation":[{"name":"Division of Neurology Department of Paediatrics The Hospital for Sick Children Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Abushama","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Paediatrics The Hospital for Sick Children Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Morrison\u2010Levy","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Paediatrics The Hospital for Sick Children Toronto Ontario Canada"},{"name":"Children's Hospital of Eastern Ottawa Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puneet","family":"Jain","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Paediatrics The Hospital for Sick Children Toronto Ontario Canada"},{"name":"Division of Pediatric Neurology Department of Pediatrics Danat Al Emarat Hospital for Women and Children Abu Dhabi United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kollencheri","family":"Puthenveettil Vinayan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Amrita Institute of Medical Sciences Cochin India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musaad","family":"Abukhalid","sequence":"additional","affiliation":[{"name":"Department of Neurosciences King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham M.","family":"Aldhalaan","sequence":"additional","affiliation":[{"name":"Department of Neurosciences King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanin S.","family":"Almuzaini","sequence":"additional","affiliation":[{"name":"Department of Neurosciences King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheffali","family":"Gulati","sequence":"additional","affiliation":[{"name":"Child Neurology Division Department of Pediatrics Center of Excellence &amp; Advanced Research on Childhood Neurodevelopmental Disorders All India Institute of Medical Sciences New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tova","family":"Hershkovitz","sequence":"additional","affiliation":[{"name":"Genetic Institute Rambam Medical Center Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Konanki","sequence":"additional","affiliation":[{"name":"Department of Neurology Rainbow Children's Hospital Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lokesh","family":"Lingappa","sequence":"additional","affiliation":[{"name":"Department of Neurology Rainbow Children's Hospital Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee F.","family":"Luat","sequence":"additional","affiliation":[{"name":"Detroit Medical Center Children's Hospital of Michigan Wayne State University School of Medicine Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shatha","family":"Shafi","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Pediatrics Prince Sultan Military Medical City Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brahim","family":"Tabarki","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Pediatrics Prince Sultan Military Medical City Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Thomas","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department of Neurological Sciences Christian Medical College Vellore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeetha","family":"Yoganathan","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department of Neurological Sciences Christian Medical College Vellore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9427-7240","authenticated-orcid":false,"given":"Majid","family":"Alfadhel","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center King Saud bin Abdulaziz University for Health Sciences King Abdulaziz Medical City Ministry of National Guard\u2010Health Affairs Riyadh Saudi Arabia"},{"name":"Division of Genetics Department of Pediatrics King Abdulaziz Medical City Ministry of National Guard\u2010Health Affairs Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0873-9718","authenticated-orcid":false,"given":"Ravindra","family":"Arya","sequence":"additional","affiliation":[{"name":"Division of Neurology Comprehensive Epilepsy Center Cincinnati Children's Hospital Medical Center Cincinnati Ohio"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Donner","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Paediatrics The Hospital for Sick Children Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salleh N.","family":"Ehaideb","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center King Saud bin Abdulaziz University for Health Sciences King Abdulaziz Medical City Ministry of National Guard\u2010Health Affairs Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vykuntaraju K.","family":"Gowda","sequence":"additional","affiliation":[{"name":"Indira Gandhi Institute of Child Health Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Jain","sequence":"additional","affiliation":[{"name":"Santokba Durlabhji Hospital Jaipur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Madaan","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Department of Pediatrics Postgraduate Institute of Medical Education and Research Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7831-4593","authenticated-orcid":false,"given":"Kenneth A.","family":"Myers","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Pediatrics Montreal Children's Hospital McGill University Health Centre Montreal Quebec Canada"},{"name":"Department of Neurology &amp; 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