Oral Findings of RASopathies in Children: Molecular Mechanisms and Clinical Spectrum with a Focus on Neurofibromatosis Type 1
TL;DR
Current evidence on the molecular basis, clinical manifestations, oral findings, diagnostic approaches, and management strategies of NF1 and related RASopathies is offered, with a focus on NF1.
Abstract
RASopathies constitute a group of inherited disorders caused by germline alterations that affect the RAS– MAPK pathway, a signaling cascade essential for regulating cellular growth and development. Among these disorders, neurofibromatosis type 1 (NF1) represents the most frequently encountered form. Other related conditions—including Noonan syndrome, its lentiginous variant, Costello syndrome, cardio-facio-cutaneous syndrome (CFCS), Legius syndrome, and capillary malformation–arteriovenous malformation syndrome—demonstrate significant genetic and phenotypic overlap. This review offers current evidence on the molecular basis, clinical manifestations, oral findings, diagnostic approaches, and management strategies of NF1 and related RASopathies. A structured literature review was performed using PubMed, Scopus, and Web of Science databases, including publications available up to June 2024. RASopathies commonly present with craniofacial abnormalities, cardiac defects, neurodevelopmental delays, and cutaneous manifestations, though each syndrome varies in genetic origin and clinical expression. Neurofibromatosis type 1 remains the most frequent, while Costello and CFCSs are comparatively rare. Oral findings—such as high-arched palate, gingival enlargement, and jawbone lesions—may serve as useful early diagnostic indicators. Recent advances in genetic testing and the emergence of targeted molecular therapies have significantly refined diagnostic accuracy and patient care. Recognizing genotype–phenotype correlations and integrating oral with systemic features are key to timely diagnosis and comprehensive management. Multidisciplinary collaboration and precision-based approaches are essential to improve long-term outcomes for individuals affected by RASopathies. Cite this article as: Kabacıoğlu E, Elçioğlu N, Kökali F, Menteş A. Oral findings of RASopathies in children: molecular mechanisms and clinical spectrum with a focus on NF1. Cerrahpaşa Med J. 2026, 50, 0094, doi: 10.5152/cjm.2026.25094.