{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T18:48:11Z","timestamp":1792694891190,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012280","name":"Rare Disease Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012280","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gene variants that dysregulate signaling through the RAS\u2010MAPK pathway cause cardiofaciocutaneous syndrome (CFCS), a rare multi\u2010system disorder. Infantile epileptic spasms syndrome (IESS) and other forms of epilepsy are among the most serious complications. To investigate clinical presentation, treatment outcomes, and genotype\u2013phenotype associations in CFCS patients with IESS, molecular genetics and clinical neurological history were reviewed across two large clinical research cohorts (<jats:italic>n<\/jats:italic>\u00a0=\u00a0180). IESS presented in 18\/180 (10%) cases, including 16 patients with <jats:italic>BRAF<\/jats:italic> variants and 2 with <jats:italic>MAP2K1<\/jats:italic> variants. Among IESS patients with <jats:italic>BRAF<\/jats:italic> variants, 16\/16 (100%) had sequence changes affecting the protein kinase domain (exons 11\u201316), although only 57% of total <jats:italic>BRAF<\/jats:italic> variants occurred in this domain. Clinical onset of spasms occurred at a median age of 5.4\u00a0months (range: 1\u201324\u2009months). Among 13\/18 patients whose IESS resolved with anti\u2010seizure medications, 10 were treated with ACTH and\/or vigabatrin. A substantial majority of CFCS patients with IESS subsequently developed other epilepsy types (16\/18; 89%). In terms of neurodevelopmental outcomes, gross motor function and verbal communication were more limited in patients with a history of IESS compared to those without IESS. These findings can inform clinical neurological care guidelines for CFCS and development of relevant pre\u2010clinical models for severe epilepsy phenotypes.<\/jats:p>","DOI":"10.1002\/ajmg.c.32022","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T07:56:20Z","timestamp":1669794980000},"page":"501-509","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Infantile epileptic spasms syndrome in children with cardiofaciocutanous syndrome: Clinical presentation and associations with genotype"],"prefix":"10.1002","volume":"190","author":[{"given":"Daniel L.","family":"Kenney\u2010Jung","sequence":"first","affiliation":[{"name":"Department of Neurology University of Minnesota Medical School  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dante J.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics 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