The authors declare no conflict of interest.
Craniofacial and dental development in cardio-facio-cutaneous syndrome: the importance of Ras signaling homeostasis
Article first published online: 27 SEP 2012
© 2012 John Wiley & Sons A/S
Volume 83, Issue 6, pages 539–544, June 2013
How to Cite
Craniofacial and dental development in cardio-facio-cutaneous syndrome: the importance of Ras signaling homeostasis., , , , , , , , , , .
- Issue published online: 23 APR 2013
- Article first published online: 27 SEP 2012
- Accepted manuscript online: 4 SEP 2012 08:11AM EST
- Manuscript Revised: 27 AUG 2012
- Manuscript Accepted: 27 AUG 2012
- Manuscript Received: 5 JUL 2012
- NIH grant. Grant Numbers: HD061140, DP2-OD007449, DP2-OD007191
- NIDCR fellowship. Grant Number: F30DE022205
- International Mental Health Research Organization
- cardio-facio-cutaneous syndrome;
- craniofacial development;
- MAPK pathway;
- receptor tyrosine kinase;
- signal transduction;
- tooth development
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.