A Review of Craniofacial and Dental Findings of the RASopathies

Objectives: RASopathies or RAS/mitogen-activated protein kinase (MAPK) syndromes are a group of disorders caused by germline mutations in genes that encode protein components of the RAS/MAPK pathway. The disruption of this pathway can cause dysmorphology, cardiovascular abnormalities, musculoskeletal abnormalities, cutaneous lesions, and neurocognitive impairment. In this narrative review, our aim was to summarize the clinical findings and highlight the reported craniofacial features of RASopathies.
Methods: We conducted an electronic search to access relevant publications and case reports. Articles in English reporting craniofacial and/or oral findings were included for this review.
Results: We summarized and compared the reported craniofacial features of RASopathies. Rasopathies overlap significantly phenotypically and in some cases it could be very significant, thereby making the diagnosis challenging. For instance, due to the significant clinical overlap of Noonan syndrome with multiple lentigines (NSML) with Noonan Syndrome and Neurofibromatosis-Noonan Syndrome, a clinical diagnosis of NSML may not be feasible, especially in infants and young children without lentigines. The presence of distinctive signs, including hypertrophic cardiomyopathy, sensorineural deafness, and café-au-lait spots could help in diagnosing NSML in these young patients.
Conclusions: Comparison of craniofacial findings could be helpful to make a differential clinical diagnosis. In some cases, genetic testing is needed for definitive diagnosis and published papers of oral, particularly dental, findings of Rasopathies is limited.