{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T01:38:09Z","timestamp":1785634689712,"version":"3.56.0"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"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":["Epileptic Disorders"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Deleterious variants in the\n                    <jats:italic>CACNA1A<\/jats:italic>\n                    gene, encoding the CaV2.1 P\/Q\u2010type voltage\u2010gated calcium channel, cause a broad spectrum of neurological disorders, including familial hemiplegic migraine, episodic ataxia, and developmental and epileptic encephalopathy (DEE). Information on genotype\u2013phenotype correlations and on the factors influencing clinical variability is still limited, hindering potential applications in precision medicine. We present three adults (aged 26, 27, and 40\u2009years) from two families with heterozygous\n                    <jats:italic>CACNA1A<\/jats:italic>\n                    deleterious variants and DEE, highlighting striking interindividual and intrafamilial variability in adult\u2010onset presentations. Genetic testing revealed two distinct pathogenic variants [p.(Val1392Met) and p.(Glu1263Lys)], including one instance of germinal\/gonosomic mosaicism in unaffected parents. The electroclinical details demonstrated profound differences, notably: a pair of siblings with the same variant showing discordant clinical severity, and an unrelated patient whose complex phenotype, dominated by cerebellar ataxia, required prolonged video\u2010EEG to accurately diagnose a high burden of subtle absence seizures. These cases significantly expand the phenotypic spectrum and highlight the critical role of comprehensive electroclinical characterization in adults with\n                    <jats:italic>CACNA1A<\/jats:italic>\n                    \u2010related DEE for personalized management.\n                  <\/jats:p>","DOI":"10.1002\/epd2.70207","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T15:22:28Z","timestamp":1771600948000},"page":"512-519","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Expanding the phenotypic spectrum of\n                    <i>CACNA1A<\/i>\n                    \u2010related developmental and epileptic encephalopathy in adults"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6583-3482","authenticated-orcid":false,"given":"Orazio","family":"Palumbo","sequence":"first","affiliation":[{"name":"UOC Genetica Medica Fondazione IRCCS Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Costantino","sequence":"additional","affiliation":[{"name":"Epilepsy Center \u2013 Neurology Unit Fondazione IRCCS Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Benvenuto","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica Fondazione IRCCS Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9498-9902","authenticated-orcid":false,"given":"Pietro","family":"Palumbo","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica Fondazione IRCCS Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Di Claudio","sequence":"additional","affiliation":[{"name":"Epilepsy Center \u2013 Neurology Unit Fondazione IRCCS Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9140-5350","authenticated-orcid":false,"given":"Paola","family":"Imbrici","sequence":"additional","affiliation":[{"name":"Department of Pharmacy \u2013 Drug Sciences University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Liantonio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy \u2013 Drug Sciences University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Carella","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica Fondazione IRCCS Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6069-0993","authenticated-orcid":false,"given":"Marco","family":"Castori","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica Fondazione IRCCS Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3465-7540","authenticated-orcid":false,"given":"Giuseppe","family":"d'Orsi","sequence":"additional","affiliation":[{"name":"Epilepsy Center \u2013 Neurology Unit Fondazione IRCCS Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1222321"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-025-06062-3"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.09.008"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62960"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.228"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516767"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2016.11.005"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.09.003"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000265"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16316"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.2129"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14180"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.148"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx081"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2832-5"}],"container-title":["Epileptic 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