{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:19:02Z","timestamp":1790295542307,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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>To characterize the clinical, electroencephalographic, and genetic features of epilepsies featuring absence seizures within monogenic etiology, highlighting the diagnostic, treatment and prognostic implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective, multicenter study including patients with monogenic epilepsies and electroencephalography (EEG)\u2013documented absence seizures. We analyzed clinical data, electroclinical findings, neurodevelopmental outcomes, and treatment responses through standardized questionnaires and medical records. We classified genetic variants according to American College of Medical Genetics and Genomics (ACMG) guidelines and performed univariate and multivariate analyses to identify predictors of developmental outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 160 patients (111 female; median age at last follow\u2010up: 13\u2009years) with absence seizures and confirmed pathogenic or likely pathogenic monogenic variants. The most frequently implicated genes were\n                      <jats:italic>SLC2A1, SLC6A1, SYNGAP1<\/jats:italic>\n                      ,\n                      <jats:italic>CHD2,<\/jats:italic>\n                      and\n                      <jats:italic>SCN1A<\/jats:italic>\n                      . Four genes\u2014\n                      <jats:italic>HESX1, NCKAP1, SON, STARD9<\/jats:italic>\n                      \u2014had not been previously associated with absence seizures. In 35% of patients, absence seizures were the only seizure type and in 67% were the initial manifestation. Atypical features included irregular EEG discharges (56%) eyelid myoclonia (42%), and automatisms (33%). Early\u2010onset (before age 3) seizures occurred in 58% and was significantly associated with atypical features (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.03). Using existing International League Against Epilepsy (ILAE) epilepsy syndrome classification, 60% of patients could not be classified. Developmental delay occurred in 54%, intellectual disability in 65%, and other neurodevelopmental comorbidities in 49%. Predictors of poor developmental outcomes included early developmental delay, drug\u2010resistant epilepsy, and early absence onset. We found no difference in the prevalence of drug resistance across the various genetic etiologies. The most effective medications for absence seizures included valproate, ethosuximide, benzodiazepines, and lamotrigine. Disease\u2010specific therapies (e.g., ketogenic diet in\n                      <jats:italic>SLC2A1<\/jats:italic>\n                      , stiripentol\/fenfluramine in\n                      <jats:italic>SCN1A)<\/jats:italic>\n                      were effective in select cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Absence seizures are a common manifestation of different monogenic epilepsies, often associated with early onset, atypical clinical and\/or EEG features, developmental delay or drug resistance. Classification models should incorporate genetic data alongside electroclinical features, especially as next\u2010generation sequencing is increasingly used.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18655","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T14:24:30Z","timestamp":1761402270000},"page":"272-290","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical and genetic landscape of epilepsies with absence seizures and single\u2010gene etiology"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-1969","authenticated-orcid":false,"given":"Simona","family":"Balestrini","sequence":"first","affiliation":[{"name":"Neuroscience and Human Genetics Department Meyer Children\u2019s Hospital IRCCS  Florence Italy"},{"name":"Department of Neuroscience, Pharmacology and Child Health University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7296-5410","authenticated-orcid":false,"given":"Ilaria","family":"Galli","sequence":"additional","affiliation":[{"name":"Neuroscience and Human Genetics Department Meyer Children\u2019s Hospital IRCCS  Florence Italy"},{"name":"Department of Neuroscience, Pharmacology and Child Health University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9144-6912","authenticated-orcid":false,"given":"Maria Luisa","family":"Ricci","sequence":"additional","affiliation":[{"name":"Neuroscience and Human Genetics Department Meyer Children\u2019s Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-7694","authenticated-orcid":false,"given":"Elena","family":"Parrini","sequence":"additional","affiliation":[{"name":"Neuroscience and Human Genetics Department Meyer Children\u2019s Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6790-6251","authenticated-orcid":false,"given":"Davide","family":"Mei","sequence":"additional","affiliation":[{"name":"Neuroscience and Human Genetics Department Meyer Children\u2019s Hospital IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7664-5807","authenticated-orcid":false,"given":"Mario","family":"Mastrangelo","sequence":"additional","affiliation":[{"name":"Department of Women\/Child Health and Urological Science Sapienza University of Rome  Rome Italy"},{"name":"Unit of Child Neurology and Psychiatry, Department of Neuroscience\/Mental Health Azienda Ospedaliero Universitaria Policlinico Umberto I\u2010 Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1083-5576","authenticated-orcid":false,"given":"Francesco","family":"Pisani","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry, Department of Neuroscience\/Mental Health Azienda Ospedaliero Universitaria Policlinico Umberto I\u2010 Rome  Rome Italy"},{"name":"Department of Human Neuroscience Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0603-0529","authenticated-orcid":false,"given":"Corinna","family":"Filippi","sequence":"additional","affiliation":[{"name":"Paediatric Neurology and Psychiatry Unit, Spedali Civili Children\u2019s Hospital University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6736-4330","authenticated-orcid":false,"given":"Lucio","family":"Giordano","sequence":"additional","affiliation":[{"name":"Paediatric Neurology and Psychiatry Unit, Spedali Civili Children\u2019s Hospital University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7177-4500","authenticated-orcid":false,"given":"Elisabetta","family":"Cesaroni","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatric Unit G. Salesi Pediatric Hospital; AOU Delle Marche  Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9212-2691","authenticated-orcid":false,"given":"Carla","family":"Marini","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatric Unit G. Salesi Pediatric Hospital; AOU Delle Marche  Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3906-555X","authenticated-orcid":false,"given":"Emanuele","family":"Cerulli Irelli","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1890-5409","authenticated-orcid":false,"given":"Carlo","family":"di Bonaventura","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3010-5216","authenticated-orcid":false,"given":"Marica","family":"Rubino","sequence":"additional","affiliation":[{"name":"Neurology Unit University Hospital Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-4293","authenticated-orcid":false,"given":"Antonietta","family":"Coppola","sequence":"additional","affiliation":[{"name":"Neurology Unit University Hospital Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-4724","authenticated-orcid":false,"given":"Jacopo","family":"Proietti","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatric Unit, Department of Engineering for Innovation Medicine University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3103-230X","authenticated-orcid":false,"given":"Tommaso Lo","family":"Barco","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatric Unit, Department of Engineering for Innovation Medicine University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1062-8438","authenticated-orcid":false,"given":"Francesca","family":"Darra","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatric Unit, Department of Engineering for Innovation Medicine University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7979-9895","authenticated-orcid":false,"given":"Laura","family":"Licchetta","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Delle Scienze Neurologiche di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1109-7296","authenticated-orcid":false,"given":"Francesca","family":"Bisulli","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Delle Scienze Neurologiche di Bologna  Bologna Italy"},{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3311-2765","authenticated-orcid":false,"given":"Marco","family":"Perulli","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Pschiatry, Dipartimento Della Salute Della Donna, Del Bambino e di Sanit\u00e0 Pubblica Fondazione Policlinico Universitario A. Gemelli, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0491-4021","authenticated-orcid":false,"given":"Domenica","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienza Della Vita e di Sanit\u00e0 Pubblica Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8526-1511","authenticated-orcid":false,"given":"Angela","family":"De Dominicis","sequence":"additional","affiliation":[{"name":"Neurology Epilepsy and Movement Disorders Unit Bambino Gesu\u2019 Children\u2019s Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9841-8581","authenticated-orcid":false,"given":"Marina","family":"Trivisano","sequence":"additional","affiliation":[{"name":"Neurology Epilepsy and Movement Disorders Unit Bambino Gesu\u2019 Children\u2019s Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8120-0287","authenticated-orcid":false,"given":"Nicola","family":"Specchio","sequence":"additional","affiliation":[{"name":"Neurology Epilepsy and Movement Disorders Unit Bambino Gesu\u2019 Children\u2019s Hospital, IRCCS  Rome Italy"},{"name":"University Hospitals KU Leuven  Leuven Belgium"}],"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 Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8505-3894","authenticated-orcid":false,"given":"Davide","family":"Caputo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience 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":"Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"LICE Collaborative group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7272-7079","authenticated-orcid":false,"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Neuroscience and Human Genetics Department Meyer Children\u2019s Hospital IRCCS  Florence Italy"},{"name":"Department of Neuroscience, Pharmacology and Child Health University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17236"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2005.00309.x"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2019.1656716"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-024-00546-6"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/98.3.427"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18338"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000228257.60184.82"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012744"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17547"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21724"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12007"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-021-01173-9"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13709"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17241"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17239"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2009.02397.x"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01777.x"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/477"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2010.06.008"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.16235"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.10.002"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.035"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1432"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00960-4"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38391"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E14-03-0829"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2015.05.022"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0130-4"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01485-w"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0248-z"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000208076"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.05.020"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.102"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23702"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2646"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006729"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(25)00032-8"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1945.02860500001001"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410130610"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2021.10341"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)03157-3"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32500-0"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.4113"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102020\u2010325932"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.18655","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.18655","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.18655","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:11:08Z","timestamp":1773000668000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.18655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,25]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/epi.18655"],"URL":"https:\/\/doi.org\/10.1111\/epi.18655","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,25]]},"assertion":[{"value":"2025-06-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}