{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:13:37Z","timestamp":1761718417847},"reference-count":56,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T00:00:00Z","timestamp":1438819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Noonan syndrome (NS) is a multiple congenital anomaly syndrome caused by germline mutations in genes coding for components of the Ras\u2010mitogen\u2010activated protein kinase (RAS\u2010MAPK) pathway. Features include short stature, characteristic facies, congenital heart anomalies, and developmental delay. While there is considerable clinical heterogeneity in NS, craniosynostosis is not a common feature of the condition. Here, we report on a 2 month\u2010old girl with Noonan syndrome associated with a de novo mutation in<jats:italic>KRAS<\/jats:italic>(p.P34Q) and premature closure of the sagittal suture. We provide a review of the literature of germline<jats:italic>KRAS<\/jats:italic>mutations and find that approximately 10% of published cases have craniosynostosis. Our findings expand on the NS phenotype and suggest that germline mutations in the<jats:italic>KRAS<\/jats:italic>gene are causally involved in craniosynostosis, supporting the role of the RAS\u2010MAPK pathway as a mediator of aberrant bone growth in cranial sutures. The inclusion of craniosynostosis as a possible phenotype in<jats:italic>KRAS<\/jats:italic>\u2010associated Noonan Syndrome has implications in the differential diagnosis and surgical management of individuals with craniosynostosis. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37259","type":"journal-article","created":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T19:48:43Z","timestamp":1438890523000},"page":"2657-2663","source":"Crossref","is-referenced-by-count":43,"title":["Craniosynostosis and Noonan syndrome with<i>KRAS<\/i>mutations: Expanding the phenotype with a case report and review of the literature"],"prefix":"10.1002","volume":"167","author":[{"given":"Yonit A.","family":"Addissie","sequence":"first","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Udhaya","family":"Kotecha","sequence":"additional","affiliation":[{"name":"Center of Medical Genetics Sir Ganga Ram Hospital New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel A.","family":"Hart","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariel F.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Kruszka","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"Muenke","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2011.07.013"},{"key":"e_1_2_6_3_1","unstructured":"AllansonJE RobertsAE.Noonan Syndrome.2001Nov 15 [Updated 2011 Aug 4]. 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