{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:57:43Z","timestamp":1787738263637,"version":"build-2784847793"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Project Ricerca Finalizzata RF\u20102019\u201012 370 491"],"award-info":[{"award-number":["Project Ricerca Finalizzata RF\u20102019\u201012 370 491"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Conditions presenting with both epilepsy and movement disorders (EPIMDs) range from relatively benign cases to severe developmental encephalopathies. However, the full clinical and genetic spectrum still needs to be better defined. The aim of this study is to describe the presentation of EPIMDs in pediatric patients with known genetic etiologies, correlating these features with age at onset and underlying pathological mechanisms to identify patterns that could improve patient management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed the clinical records of pediatric patients who underwent genetic testing for EPIMDs at our institution between 2009 and 2022. Genetic testing included single\u2010gene Sanger sequencing, multigene next\u2010generation sequencing panels targeting epilepsy and\/or MDs, and array comparative genome hybridization. Demographic, clinical, and electroencephalography (EEG) data were collected. Statistical analyses were conducted using multivariate and cluster analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 97 subjects were included. The mean age \u00b1 SD at epilepsy onset was 3.6\u2009\u00b1\u20094.4\u2009years, whereas the mean age at MD onset was 5.2\u2009\u00b1\u20094.9\u2009years. Based on the mechanism of genetic dysfunction, we identified six groups: transportopathies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200918), synaptopathies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200911), channelopathies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200918), metabolic disorders (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200915), intracellular trafficking defects (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098), and unknown\/complex function disorders (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200927). Cluster analysis identified three distinct groups: (1) early\u2010onset epilepsy and paroxysmal MDs with normal intelligence quotient (IQ) and mild intellectual disability, associated with transportopathies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200938); (2) early\u2010onset epilepsy with dystonia and myoclonus, low IQ, and developmental and epileptic encephalopathy, associated with channelopathies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200931); (3) epilepsy onset between 1 and 5\u2009years of age with developmental delay, parkinsonism, and low IQ, associated with metabolic etiology (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200926).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Our study demonstrates that, despite the phenotypic and genetic pleiotropy observed in EPIMDs, a precise characterization of semiological and cognitive features remains essential to support variant interpretation and to refine the diagnostic process and patient management in these rare conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18669","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T09:35:02Z","timestamp":1761298502000},"page":"299-314","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic complexity in pediatric onset epilepsy\u2010movement disorder syndromes: Insights from a cohort of 97 subjects"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8505-3894","authenticated-orcid":false,"given":"Davide","family":"Caputo","sequence":"first","affiliation":[{"name":"Department of Pediatric Neuroscience, European Reference Network EPIcare Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-3328","authenticated-orcid":false,"given":"Roberta","family":"Solazzi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience, European Reference Network EPIcare Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-3041","authenticated-orcid":false,"given":"Barbara","family":"Castellotti","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste","family":"Panteghini","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Luisa","family":"Sciacca","sequence":"additional","affiliation":[{"name":"Laboratory of Cytogenetic, Neurological Biochemistry and Neuropharmacology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Visani","sequence":"additional","affiliation":[{"name":"Epilepsy Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Freri","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience, European Reference Network EPIcare Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ragona","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience, European Reference Network EPIcare Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5385-761X","authenticated-orcid":false,"given":"Laura","family":"Canafoglia","sequence":"additional","affiliation":[{"name":"Integrated Diagnostics for Epilepsy, Department of Diagnostic and Technology, European Reference Network EPIcare Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Zibordi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience, European Reference Network EPIcare Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-5365","authenticated-orcid":false,"given":"Giovanna","family":"Zorzi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience, European Reference Network EPIcare Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6936-623X","authenticated-orcid":false,"given":"Shari","family":"Gandelli","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience, European Reference Network EPIcare Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Gellera","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Franceschetti","sequence":"additional","affiliation":[{"name":"Neurophysiology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan 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