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Review
. 2017 Jun;20 Suppl 1(Suppl 1):32-38.
doi: 10.1111/ocr.12144.

A review of craniofacial and dental findings of the RASopathies

H Cao  1   2 , N Alrejaye  2 , O D Klein  2   3 , A F Goodwin  2 , S Oberoi  2
Affiliations
Review

A review of craniofacial and dental findings of the RASopathies

H Cao et al. Orthod Craniofac Res. 2017 Jun.

Abstract

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.

Keywords: RASopathy; Ras/MAPK pathway; craniofacial development; dental anomalies; malocclusion.

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Conflict of interest statement

Conflict of interest

No conflict of interest to declare

Figures

Figure 1
Figure 1. Syndromes of the Ras pathway
Schematic representation of the Ras signaling pathway. Each syndrome is represented by a color, and the protein in the pathway encoded by the causative mutated gene is illustrated in that color.
Figure 2
Figure 2. Craniofacial features of NS, CS, and CFC
Frontal and profile photographs of (A) a 15-year-old male and (B) 31-year-old female with NS, (C) 26-year-old male and (D) 17-year-old female with CS, and (E) 12-year-old male and (F) 17-year-old female with CFC.
Figure 3
Figure 3. Dental characteristics of NS, CS, and CFC
(A, C, E) Open bite. Black arrows point to mamelons, which are normally abraded by contact. (B, D, F) Posterior crossbite (demarcated by white arrows). (B) Individuals with NS present with expected incidence of class I occlusion and class II malocclusion as shown by black arrow demarcating maxillary canine cusp tip anterior relative to the contact between the mandibular canine and first premolar (black line). (D) CS individuals have higher incidence of class III malocclusion with the maxillary canine (black arrow) posterior to the contact (black line) while (F) CFC individuals present with normal distribution of class I occlusion with the maxillary canine (black arrow) in line with the contact (black line) or class II malocclusion (as shown in B).
See this image and copyright information in PMC

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