{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T18:20:34Z","timestamp":1778178034518,"version":"3.51.4"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,3,25]],"date-time":"2014-03-25T00:00:00Z","timestamp":1395705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Costello syndrome (CS) is a RASopathy characterized by a wide range of cardiac, musculoskeletal, dermatological, and developmental abnormalities. The RASopathies are defined as a group of syndromes caused by activated Ras\/mitogen\u2010activated protein kinase (MAPK) signaling. Specifically, CS is caused by activating mutations in <jats:italic>HRAS<\/jats:italic>. Although receptor tyrosine kinase (RTK) signaling, which is upstream of Ras\/MAPK, is known to play a critical role in craniofacial and dental development, the craniofacial and dental features of CS have not been systematically defined in a large group of individuals. In order to address this gap in our understanding and fully characterize the CS phenotype, we evaluated the craniofacial and dental phenotype in a large cohort (n\u2009=\u200941) of CS individuals. We confirmed that the craniofacial features common in CS include macrocephaly, bitemporal narrowing, convex facial profile, full cheeks, and large mouth. Additionally, CS patients have a characteristic dental phenotype that includes malocclusion with anterior open bite and posterior crossbite, enamel hypo\u2010mineralization, delayed tooth development and eruption, gingival hyperplasia, thickening of the alveolar ridge, and high palate. Comparison of the craniofacial and dental phenotype in CS with other RASopathies, such as cardio\u2010facio\u2010cutaneous syndrome (CFC), provides insight into the complexities of Ras\/MAPK signaling in human craniofacial and dental development. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36475","type":"journal-article","created":{"date-parts":[[2014,3,25]],"date-time":"2014-03-25T16:53:07Z","timestamp":1395766387000},"page":"1425-1430","source":"Crossref","is-referenced-by-count":29,"title":["Craniofacial and dental development in Costello syndrome"],"prefix":"10.1002","volume":"164","author":[{"given":"Alice F.","family":"Goodwin","sequence":"first","affiliation":[{"name":"Program in Craniofacial and Mesenchymal Biology, and Division of Craniofacial Anomalies, Department of Orofacial Sciences University of California San Francisco San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Snehlata","family":"Oberoi","sequence":"additional","affiliation":[{"name":"Program in Craniofacial and Mesenchymal Biology, and Division of Craniofacial Anomalies, Department of Orofacial Sciences University of California San Francisco San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Landan","sequence":"additional","affiliation":[{"name":"Program in Craniofacial and Mesenchymal Biology, and Division of Craniofacial Anomalies, Department of Orofacial Sciences University of California San Francisco San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyril","family":"Charles","sequence":"additional","affiliation":[{"name":"Program in Craniofacial and Mesenchymal Biology, and Division of Craniofacial Anomalies, Department of Orofacial Sciences University of California San Francisco San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica C.","family":"Massie","sequence":"additional","affiliation":[{"name":"Program in Craniofacial and Mesenchymal Biology, and Division of Craniofacial Anomalies, Department of Orofacial Sciences University of California San Francisco San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Fairley","sequence":"additional","affiliation":[{"name":"Program in Craniofacial and Mesenchymal Biology, and Division of Craniofacial Anomalies, Department of Orofacial Sciences University of California San Francisco San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine A.","family":"Rauen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Institute for Human Genetics University of California San Francisco San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ophir 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