{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:27:44Z","timestamp":1793363264983,"version":"4.5.0"},"reference-count":72,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Cardiofaciocutaneous (CFC) syndrome is one of the rarest RASopathies characterized by multiple congenital ectodermal, cardiac and craniofacial abnormalities with a mild to severe ocular, gastrointestinal and neurological involvement. It is an autosomal dominant syndrome, with complete penetrance, caused by heterozygous pathogenic variants in the genes BRAF, MAP2K1\/MEK1, MAP2K2\/MEK2, KRAS or, rarely, YWHAZ, all part of the RAS-MAPK pathway. This pathway is a signal transduction cascade that plays a crucial role in normal cellular processes such as cell growth, proliferation, differentiation, survival, metabolism and migration. CFC syndrome overlaps with Noonan syndrome, Costello syndrome, neurofibromatosis type 1 and Legius syndrome, therefore making the diagnosis challenging. Neurological involvement in CFC is more severe than in other RASopathies. Phenotypic variability in CFC patients is related to the specific gene affected, without a recognized genotype\u2013phenotype correlation for distinct pathogenic variants. Currently, there is no specific treatment for CFC syndrome. Encouraging zebrafish model system studies suggested that, in the future, MEK inhibitors could be a suitable treatment of progressive phenotypes of CFC in children. A multidisciplinary care is necessary for appropriate medical management.<\/jats:p>","DOI":"10.3390\/genes14122111","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T08:47:43Z","timestamp":1700642863000},"page":"2111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The Cardiofaciocutaneous Syndrome: From Genetics to Prognostic\u2013Therapeutic Implications"],"prefix":"10.3390","volume":"14","author":[{"given":"Giovanna","family":"Scorrano","sequence":"first","affiliation":[{"name":"Department of Pediatrics, \u201cG. D\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"David","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, \u201cSapienza\u201d University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9826-4490","authenticated-orcid":false,"given":"Elisa","family":"Cal\u00ec","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Chimenz","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology and Dialysis Unit, University Hospital \u201cG. Martino\u201d, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1244-0789","authenticated-orcid":false,"given":"Saverio","family":"La Bella","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, \u201cG. D\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2644-1475","authenticated-orcid":false,"given":"Armando","family":"Di Ludovico","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, \u201cG. D\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Di Rosa","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit, Department of Human Pathology in Adult and Developmental Age \u201cGaetano Barresi\u201d, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloisa","family":"Gitto","sequence":"additional","affiliation":[{"name":"Neonatal and Pediatric Intensive Care Unit, Department of Human Pathology of the Adult and Developmental Age \u201cGaetano Barresi\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kshitij","family":"Mankad","sequence":"additional","affiliation":[{"name":"Department of Radiology, Great Ormond Street Hospital for Children, London WC1N 3JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria","family":"Nardello","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialities, \u201cG. D\u2019Alessandro\u201d University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6541-3170","authenticated-orcid":false,"given":"Giuseppe Donato","family":"Mangano","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialities, \u201cG. D\u2019Alessandro\u201d University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4089-637X","authenticated-orcid":false,"given":"Chiara","family":"Leoni","sequence":"additional","affiliation":[{"name":"Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Ceravolo","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"dmm049107","DOI":"10.1242\/dmm.049107","article-title":"The RASopathies: From pathogenetics to therapeutics","volume":"15","author":"Hebron","year":"2022","journal-title":"Dis. Models Mech."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/ajmg.a.35292","article-title":"Prevalence and clinical features of Costello syndrome and cardio-facio-cutaneous syndrome in Japan: Findings from a nationwide epidemiological survey","volume":"158","author":"Abe","year":"2012","journal-title":"Am. J. Med. Genet. 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