title: Craniofacial and dental development in cardio-facio-cutaneous syndrome: the importance of Ras signaling homeostasis.
abstract: Cardio-facio-cutaneous syndrome (CFC) is a RASopathy that is characterized by craniofacial, dermatologic, gastrointestinal, ocular, cardiac, and neurologic anomalies. CFC is caused by activating mutations in the Ras/mitogen-activated protein kinase (MAPK) signaling pathway that is downstream of receptor tyrosine kinase (RTK) signaling. RTK signaling is known to play a central role in craniofacial and dental development, but to date, no studies have systematically examined individuals with CFC to define key craniofacial and dental features. To fill this critical gap in our knowledge, we evaluated the craniofacial and dental phenotype of a large cohort (n = 32) of CFC individuals who attended the 2009 and 2011 CFC International Family Conferences. We quantified common craniofacial features in CFC which include macrocephaly, bitemporal narrowing, convex facial profile, and hypoplastic supraorbital ridges. In addition, there is a characteristic dental phenotype in CFC syndrome that includes malocclusion with open bite, posterior crossbite, and a high-arched palate. This thorough evaluation of the craniofacial and dental phenotype in CFC individuals provides a step forward in our understanding of the role of RTK/MAPK signaling in human craniofacial development and will aid clinicians who treat patients with CFC.
authors.affiliation: Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Goodwin
authors.forename: S
authors.initials: S
authors.lastname: Oberoi
authors.forename: M
authors.initials: M
authors.lastname: Landan
authors.forename: C
authors.initials: C
authors.lastname: Charles
authors.forename: J
authors.initials: J
authors.lastname: Groth
authors.forename: A
authors.initials: A
authors.lastname: Martinez
authors.forename: C
authors.initials: C
authors.lastname: Fairley
authors.forename: L A
authors.initials: LA
authors.lastname: Weiss
authors.forename: W E
authors.initials: WE
authors.lastname: Tidyman
authors.forename: O D
authors.initials: OD
authors.lastname: Klein
authors.forename: K A
authors.initials: KA
authors.lastname: Rauen
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019465:Craniofacial Abnormalities / Q000473:pathology*; D004476:Ectodermal Dysplasia / Q000235:genetics / Q000473:pathology*; D019066:Facies; D005183:Failure to Thrive / Q000235:genetics / Q000473:pathology*; D005260:Female; D005838:Genotype; D006330:Heart Defects, Congenital / Q000235:genetics / Q000473:pathology*; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000235:genetics; D048370:MAP Kinase Kinase 2 / Q000235:genetics; D008297:Male; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction / Q000235:genetics; D013577:Syndrome; D014071:Tooth Abnormalities / Q000473:pathology*; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482128:MAP2K2 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins