{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:06:37Z","timestamp":1790723197758,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T00:00:00Z","timestamp":1498176000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["K12\u2010DE023574"],"award-info":[{"award-number":["K12\u2010DE023574"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R35\u2010DE026602"],"award-info":[{"award-number":["R35\u2010DE026602"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005648","name":"American Association of Orthodontists Foundation","doi-asserted-by":"publisher","award":["PFA"],"award-info":[{"award-number":["PFA"]}],"id":[{"id":"10.13039\/100005648","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Orthod Craniofacial Res"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>opathies are a group of syndromes that have in common germline mutations in genes that encode components of the Ras\/mitogen\u2010activated protein kinase (MAPK) pathway and have been a focus of study to understand the role of this pathway in development and disease. These syndromes include Noonan syndrome (<jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>), Noonan syndrome with multiple lentigines (<jats:styled-content style=\"fixed-case\">NSML<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">LEOPARD<\/jats:styled-content> syndrome), neurofibromatosis type 1 (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>1), Costello syndrome (<jats:styled-content style=\"fixed-case\">CS<\/jats:styled-content>), cardio\u2010facio\u2010cutaneous (<jats:styled-content style=\"fixed-case\">CFC<\/jats:styled-content>) syndrome, neurofibromatosis type 1\u2010like syndrome (<jats:styled-content style=\"fixed-case\">NFLS<\/jats:styled-content> or Legius syndrome) and capillary malformation\u2010arteriovenous malformation syndrome (<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">AVM<\/jats:styled-content>). These disorders affect multiple systems, including the craniofacial complex. Although the craniofacial features have been well described and can aid in clinical diagnosis, the dental phenotypes have not been analysed in detail for each of the <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>opathies. In this review, we summarize the clinical features of the <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>opathies, highlighting the reported craniofacial and dental findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Review of the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Each of the <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>opathies reviewed, caused by mutations in genes that encode different proteins in the Ras pathway, have unique and overlapping craniofacial and dental characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Careful description of craniofacial and dental features of the <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>opathies can provide information for dental clinicians treating these individuals and can also give insight into the role of Ras signalling in craniofacial development.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ocr.12144","type":"journal-article","created":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T20:56:31Z","timestamp":1498251391000},"page":"32-38","source":"Crossref","is-referenced-by-count":54,"title":["A review of craniofacial and dental findings of the RASopathies"],"prefix":"10.1111","volume":"20","author":[{"given":"H.","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery State Key Laboratory of Oral Diseases and Branch of Cleft Lip and Palate Surgery West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"Department of Orofacial Sciences and Program in Craniofacial Biology University of California, San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Alrejaye","sequence":"additional","affiliation":[{"name":"Department of Orofacial Sciences and Program in Craniofacial Biology University of California, San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O. D.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Orofacial Sciences and Program in Craniofacial Biology University of California, San Francisco  San Francisco CA USA"},{"name":"Department of Pediatrics and Institute for Medical Genetics University of California, San\u00a0Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9099-1471","authenticated-orcid":false,"given":"A. F.","family":"Goodwin","sequence":"additional","affiliation":[{"name":"Department of Orofacial Sciences and Program in Craniofacial Biology University of California, San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Oberoi","sequence":"additional","affiliation":[{"name":"Department of Orofacial Sciences and Program in Craniofacial Biology University of California, San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,23]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.114"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20748"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw191"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-091212-153523"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30138"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/000992289403300907"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000243782"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.021"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2010.09.002"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35493"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-3207"},{"key":"e_1_2_5_13_1","first-page":"1503","article-title":"Oral manifestations of Noonan syndrome: review of the literature and a report of four cases","volume":"55","author":"Mallineni SK","year":"2014","journal-title":"Rom J Morphol Embryol"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/2141-9248.160190"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-3-13"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1288\/00005537-197110000-00015"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31156"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.4103\/0970-4388.149008"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1601-0825.2001.70311.x"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/SCS.0000000000000616"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2007.03.055"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2016.03.003"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1010-5182(02)00160-9"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.PRS.0000049646.25757.BE"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2007.00743.x"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36475"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt455"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-3189"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320250303"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1749"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12005"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22152"},{"key":"e_1_2_5_33_1","volume-title":"GeneReviews\u00ae [Internet]","author":"Stevenson D","year":"1993"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13052-015-0115-9"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1086\/379793"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37613"}],"container-title":["Orthodontics &amp; Craniofacial Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Focr.12144","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ocr.12144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T18:38:02Z","timestamp":1694630282000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ocr.12144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6]]},"references-count":35,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1111\/ocr.12144"],"URL":"https:\/\/doi.org\/10.1111\/ocr.12144","archive":["Portico"],"relation":{},"ISSN":["1601-6335","1601-6343"],"issn-type":[{"value":"1601-6335","type":"print"},{"value":"1601-6343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6]]}}}