{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:38:57Z","timestamp":1792471137911,"version":"4.5.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"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 Open"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Neurodevelopmental disorders (NDDs) and epilepsy are often associated. Increasing evidence highlights a pivotal role for pathogenic variants in genes encoding synaptic scaffolding proteins. Within this group,\n                      <jats:italic>TANC2<\/jats:italic>\n                      has recently been implicated in intellectual developmental disorder with autistic features and language delay, with or without seizures; however, its full clinical spectrum and contribution to specific epileptic encephalopathies remain incompletely defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We describe the electroclinical and developmental features of three patients carrying truncating\n                      <jats:italic>TANC2<\/jats:italic>\n                      variants identified through trio\u2010exome sequencing within the European collaborative platform NETRE. Clinical, neuropsychological, and EEG data were collected and compared with prior reports.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Case #1 met Lennox\u2013Gastaut syndrome (LGS) criteria, showing early drug resistance followed by partial cognitive recovery and sustained seizure control on felbamate monotherapy. Case #2 presented with ASD and multiple seizure types\u2014including focal, atypical absence, and tonic\u2014finally reaching prolonged remission and borderline intellectual functioning. Case #3 showed early\u2010onset, drug\u2010resistant polymorphic seizures with persistent bifrontal epileptiform discharges and severe developmental impairment, consistent with an LGS\u2010like phenotype, with seizure freedom achieved under a limited polytherapy regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Our findings expand the electroclinical spectrum of\n                      <jats:italic>TANC2<\/jats:italic>\n                      \u2010related disorders, supporting a continuum ranging from NDD\u2010associated epilepsy to DEE, including LGS in selected patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TANC2<\/jats:italic>\n                      is a gene involved in brain development and synaptic function. Changes in this gene have been linked to neurodevelopmental disorders, autism, intellectual disability, and epilepsy. We describe three individuals with previously unreported truncating\n                      <jats:italic>TANC2<\/jats:italic>\n                      variants and different epilepsy phenotypes, including one patient fulfilling criteria for Lennox\u2013Gastaut syndrome (LGS) and another with LGS\u2010like features. Although seizures were initially difficult to treat in some cases, seizure control was eventually achieved. These findings expand the known clinical spectrum of\n                      <jats:italic>TANC2<\/jats:italic>\n                      \u2010related disorders and suggest that selected patients may have a more favorable seizure course than expected.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70303","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T15:36:07Z","timestamp":1783092967000},"page":"1513-1524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expanding the electroclinical spectrum of\n                    <scp>\n                      <i>TANC2<\/i>\n                    <\/scp>\n                    \u2010related disorders: Lennox\u2013Gastaut syndrome and related developmental epileptic phenotypes"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8630-6718","authenticated-orcid":false,"given":"Lorenzo","family":"Perilli","sequence":"first","affiliation":[{"name":"Clinical Pediatrics, Department of Molecular Medicine and Development, Azienda Ospedaliero\u2010Universitaria Senese University of Siena  Siena Italy"},{"name":"Department of Neurosciences Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI) University of Genoa  Genoa Italy"},{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-3711","authenticated-orcid":false,"given":"Carlotta","family":"Stipa","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Delle Scienze Neurologiche di Bologna European Reference Network for Rare and Complex Epilepsies (EpiCARE)  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5189-2161","authenticated-orcid":false,"given":"Gianmichele","family":"Villano","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI) University of Genoa  Genoa 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 European Reference Network for Rare and Complex Epilepsies (EpiCARE)  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Strothmann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Hospital Kassel  Kassel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8285-9155","authenticated-orcid":false,"given":"Robin Tobias","family":"Jauss","sequence":"additional","affiliation":[{"name":"University of Leipzig Medical Center, Institute of Human Genetics Philipp\u2010Rosenthal\u2010Stra\u00dfe 55  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard Josef","family":"Kluger","sequence":"additional","affiliation":[{"name":"Children Hospital, Research Institute Rehabilitation, Transition and Palliation\u201c PMU Salzburg  Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8190-8517","authenticated-orcid":false,"given":"Raffaella","family":"Minardi","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Delle Scienze Neurologiche di Bologna European Reference Network for Rare and Complex Epilepsies (EpiCARE)  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"NETRE consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Gobbi","sequence":"additional","affiliation":[{"name":"Associazione Famiglie LGS Italia  Correggio Italy"},{"name":"Or.S.A  Treviso Italy"},{"name":"Associazione Sclerosi Tuberosa  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0974-0596","authenticated-orcid":false,"given":"Salvatore","family":"Grosso","sequence":"additional","affiliation":[{"name":"Clinical Pediatrics, Department of Molecular Medicine and Development, Azienda Ospedaliero\u2010Universitaria Senese University of Siena  Siena 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 European Reference Network for Rare and Complex Epilepsies (EpiCARE)  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-1476","authenticated-orcid":false,"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI) University of Genoa  Genoa Italy"},{"name":"Pediatric Neurology and Muscular Diseases Unit IRCCS Istituto \u201cGiannina Gaslini\u201d, Full Member of EPICARE  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"e_1_2_18_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218290"},{"key":"e_1_2_18_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00063.2021"},{"key":"e_1_2_18_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3708"},{"key":"e_1_2_18_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2012.02.002"},{"key":"e_1_2_18_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252211982"},{"key":"e_1_2_18_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.02.001"},{"key":"e_1_2_18_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2012.05.013"},{"key":"e_1_2_18_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.06.071"},{"key":"e_1_2_18_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2025.1515304"},{"key":"e_1_2_18_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2026.1794137"},{"key":"e_1_2_18_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.806516"},{"key":"e_1_2_18_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/neurolint17010014"},{"key":"e_1_2_18_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3128-10.2010"},{"key":"e_1_2_18_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18358"},{"key":"e_1_2_18_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.847549"},{"key":"e_1_2_18_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.2880"},{"key":"e_1_2_18_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01159-0"},{"key":"e_1_2_18_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12435-8"},{"key":"e_1_2_18_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/epd2.70219"},{"key":"e_1_2_18_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-021-03021-3"},{"key":"e_1_2_18_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14569"},{"key":"e_1_2_18_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-021-01133-3"},{"key":"e_1_2_18_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17241"},{"key":"e_1_2_18_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a08f6a"},{"key":"e_1_2_18_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12682"},{"key":"e_1_2_18_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22908-4"},{"key":"e_1_2_18_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.7"},{"key":"e_1_2_18_29_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn511374\u201020240313\u201000171"}],"container-title":["Epilepsia 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