{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:02:29Z","timestamp":1790708549978,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Developmental and epileptic encephalopathies (DEEs) comprise a clinically and genetically heterogeneous group of severe neurodevelopmental disorders, frequently caused by pathogenic variants in genes encoding neuronal ion channels or synaptic proteins. The fibroblast growth\u2010factor 12 (\n                    <jats:italic>FGF12<\/jats:italic>\n                    ) encodes a binding protein for voltage\u2010gated sodium channels. Variants in\n                    <jats:italic>FGF12<\/jats:italic>\n                    have recently been associated with autosomal dominant DEEs characterized by early\u2010onset epilepsy and neurodevelopmental impairment. We report three patients with a duplication involving exons 1\u20134 of\n                    <jats:italic>FGF12<\/jats:italic>\n                    on chromosome 3q28\u2013q29 and systematically review 24 previously published cases of\n                    <jats:italic>FGF12<\/jats:italic>\n                    \u2010related DEE. Clinical features, electroencephalographic findings, neuroimaging data, and responses to anti\u2010seizure medications (ASMs) were analyzed across a total cohort of 27 patients. Eighteen patients carried\n                    <jats:italic>FGF12<\/jats:italic>\n                    missense variants, including the recurrent pathogenic p.Arg114His variant (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200914), p.Gly112Ser (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092), p.Glu87Lys (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091), and one exon 4 missense variant (chr3:g.192335434C&gt;T). Nine patients had copy number duplications involving\n                    <jats:italic>FGF12<\/jats:italic>\n                    . Seizure onset ranged from 1 day to 4\u2009years of age, with 54.1% presenting in the neonatal period. Tonic seizures were the most common seizure type, and 79.1% of patients exhibited moderate to severe intellectual disability. Brain MRI showed mild cerebral and\/or cerebellar atrophy in 41.6% of cases. Across reported cases, variable responsiveness to ASMs was observed, with sodium channel blockers including carbamazepine and phenytoin frequently associated with seizure reduction. This study expands the clinical and genetic spectrum of\n                    <jats:italic>FGF12<\/jats:italic>\n                    \u2010related DEE and highlights considerable phenotypic variability across variant types. While treatment responses were heterogeneous, sodium channel blockers were commonly associated with clinical improvement. These findings support cautious consideration of sodium channel targeting therapies in\n                    <jats:italic>FGF12<\/jats:italic>\n                    \u2010DEE and underscore the need for systematic studies to better define genotype treatment relationships.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70182","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:50:04Z","timestamp":1777524604000},"page":"2199-2210","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>FGF12<\/i>\n                    \u2010Related Early\u2010Onset Epileptic Encephalopathies: Therapeutic Response to Sodium Channel Blockers"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4559-3084","authenticated-orcid":false,"given":"Fatimah","family":"Aldurayhim","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology King Fahad Specialist Hospital  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-6825","authenticated-orcid":false,"given":"Sulman","family":"Basit","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Taibah University Medina  Almadinah Almunawwarrah Saudi Arabia"},{"name":"Center for Genetics and Inherited Diseases, Taibah University Medina  Almadinah Almunawwarrah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-6895","authenticated-orcid":false,"given":"Shahid","family":"Bashir","sequence":"additional","affiliation":[{"name":"Research Center, King Fahad Specialist Hospital  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef Hussain","family":"Housawi","sequence":"additional","affiliation":[{"name":"Department of Genetics King Fahad Specialist Hospital  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9039-2797","authenticated-orcid":false,"given":"Ali","family":"Mir","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology King Fahad Specialist Hospital  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000115"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102014\u2010102608"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.224204"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14698"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18609"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.07.006"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000120"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202302025"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13592"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.53906"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13709"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","unstructured":"Scheffer I. 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