Craniosynostosis and Noonan syndrome with KRAS mutations: Expanding the phenotype with a case report and review of the literature.

Noonan syndrome(NS) is a multiple congenital anomaly syndrome caused by germline mutationsin genes coding for components of the Ras- mitogen-activated protein kinase(RAS-MAPK) pathway. Features include short stature, characteristic facies, congenital heart anomalies, and developmental delay. While there is considerable clinical heterogeneity in NS, craniosynostosisis not a common feature of the condition. Here, we report on a 2 month-old girl with Noonan syndromeassociated with a de novo mutationin KRAS(p.P34Q) and premature closure of the sagittal suture. We provide a review of the literature of germline KRASmutations and find that approximately 10% of published cases have craniosynostosis. Our findings expand on the NS phenotype and suggest that germline mutationsin the KRASgene are causally involved in craniosynostosis, supporting the role of the RAS-MAPK pathway as a mediator of aberrant bone growth in cranial sutures. The inclusion of craniosynostosisas a possible phenotype in KRAS-associated Noonan Syndromehas implications in the differential diagnosis and surgical management of individuals with craniosynostosis. © 2015 Wiley Periodicals, Inc.