A review of craniofacial and dental findings of the RASopathies

• Published in: Orthodontics & craniofacial research Vol. 20; no. S1; pp. 32 - 38
• Main Authors: Cao, H., Alrejaye, N., Klein, O. D., Goodwin, A. F., Oberoi, S.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2017
• Subjects: Arteriovenous Malformations - genetics; Cafe-au-Lait Spots - genetics; Capillaries - abnormalities; Costello Syndrome; Craniofacial Abnormalities - genetics; craniofacial development; Craniofacial growth; dental anomalies; Ectodermal Dysplasia - genetics; Facies; Failure to Thrive - genetics; Genetic disorders; Germ-Line Mutation; Heart Defects, Congenital - genetics; Humans; Kinases; LEOPARD Syndrome; Literature reviews; malocclusion; MAP kinase; MAP Kinase Signaling System - genetics; Mutation; Neurofibromatosis; Neurofibromatosis 1 - genetics; Neurological disorders; Noonan Syndrome - genetics; Noonan's syndrome; Port-Wine Stain - genetics; Protein kinase; Ras protein; ras Proteins - genetics; Ras/MAPK pathway; RASopathy; Recklinghausen's disease; Reviews; Signal transduction; Tumors; Ras/MAPK pathway; craniofacial development; RASopathy; dental anomalies; malocclusion
• ISSN: 1601-6335; 1601-6343
• DOI: 10.1111/ocr.12144

Objectives The RASopathies are a group of syndromes that have in common germline mutations in genes that encode components of the Ras/mitogen‐activated protein kinase (MAPK) pathway and have been a focus of study to understand the role of this pathway in development and disease. These syndromes include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML or LEOPARD syndrome), neurofibromatosis type 1 (NF1), Costello syndrome (CS), cardio‐facio‐cutaneous (CFC) syndrome, neurofibromatosis type 1‐like syndrome (NFLS or Legius syndrome) and capillary malformation‐arteriovenous malformation syndrome (CM‐AVM). These disorders affect multiple systems, including the craniofacial complex. Although the craniofacial features have been well described and can aid in clinical diagnosis, the dental phenotypes have not been analysed in detail for each of the RASopathies. In this review, we summarize the clinical features of the RASopathies, highlighting the reported craniofacial and dental findings. Methods Review of the literature. Results Each of the RASopathies reviewed, caused by mutations in genes that encode different proteins in the Ras pathway, have unique and overlapping craniofacial and dental characteristics. Conclusions Careful description of craniofacial and dental features of the RASopathies can provide information for dental clinicians treating these individuals and can also give insight into the role of Ras signalling in craniofacial development.