{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:54:08Z","timestamp":1788368048049,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K02 NS112600"],"award-info":[{"award-number":["K02 NS112600"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K23 NS140491\u201001A1"],"award-info":[{"award-number":["K23 NS140491\u201001A1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS127830\u201001A1"],"award-info":[{"award-number":["R01 NS127830\u201001A1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS131512\u201001"],"award-info":[{"award-number":["R01 NS131512\u201001"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Biallelic variants in\n                      <jats:italic>TBC1D24<\/jats:italic>\n                      represent a rare cause of epilepsy and neurodevelopmental disorders, including severe developmental and epileptic encephalopathies. Here, we present the first attempt to delineate the longitudinal disease histories and effectiveness of antiseizure medications (ASMs) in\n                      <jats:italic>TBC1D24<\/jats:italic>\n                      \u2010related disorders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed an analysis of the electronic medical record data of 15 individuals with\n                      <jats:italic>TBC1D24<\/jats:italic>\n                      \u2010related disorders. Using the Human Phenotype Ontology, we recorded neurological histories and medication responses across 197 patient\u2010years of information.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Individuals with\n                      <jats:italic>TBC1D24<\/jats:italic>\n                      \u2010related disorders presented with a range of seizure types with a median age at seizure onset of 3\u2009months\u2014most frequently (73%) with focal myoclonic seizures both sparing and impairing consciousness. We report the maximum prevalence (MP) of various features as percentages of individuals reporting a given phenotype at that time point, compared to all those with available data at that time point. MP of focal seizures was at 6.25 and 7.75\u2009years of age (88%), myoclonic seizures (focal and generalized) between 9 and 10\u2009years of age (80%), and status epilepticus at 9 and 11\u2009months of age (90%). Individuals also presented with a range of movement disorders. The MP of non\u2010epileptic myoclonus was 100% at 1 and 17\u2009months of age, tremor at 14\u2009months of age (67%), ataxia at 7.25\u2009years of age (45%), and episodic hemiplegia at 3.25\u2009years of age (20%). The use of phenobarbital, oxcarbazepine, and topiramate showed the most promise in seizure management when compared to other ASMs. Everolimus, phenobarbital, and oxcarbazepine proved more effective in maintaining seizure freedom or reducing seizure frequencies in focal and myoclonic seizures compared to other ASMs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TBC1D24<\/jats:italic>\n                      \u2010related disorders are characterized by severe and pharmacoresistant epilepsy, with status epilepticus, focal seizures, and myoclonic seizures early in life. This study offers novel insights into the longitudinal disease course and treatment response in\n                      <jats:italic>TBC1D24<\/jats:italic>\n                      \u2010related disorders, a critical first step toward clinical trial readiness.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.70013","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T07:36:04Z","timestamp":1762846564000},"page":"1386-1397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical trajectories and medication response in\n                    <i>TBC1D24<\/i>\n                    \u2010related epilepsies"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0569-1459","authenticated-orcid":false,"given":"Ealing","family":"Mondragon","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Department of Neurology University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7290-4939","authenticated-orcid":false,"given":"Jan H.","family":"Magielski","sequence":"additional","affiliation":[{"name":"Division of Neurology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Biomedical and Health Informatics (DBHi) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5150-4932","authenticated-orcid":false,"given":"Bintou","family":"Bane","sequence":"additional","affiliation":[{"name":"Division of Neurology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Biomedical and Health Informatics (DBHi) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoeyLynn","family":"Nolan","sequence":"additional","affiliation":[{"name":"Division of Neurology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"TBC1D24 Foundation  Milford Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-0750","authenticated-orcid":false,"given":"Sarah M.","family":"Ruggiero","sequence":"additional","affiliation":[{"name":"Division of Neurology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Biomedical and Health Informatics (DBHi) Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8395-5587","authenticated-orcid":false,"given":"Dallas","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Department of Neurology University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6249-5585","authenticated-orcid":false,"given":"Susan","family":"Arnold","sequence":"additional","affiliation":[{"name":"Yale Medicine  New Haven Connecticut 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