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The most common cardiovascular abnormalities include pulmonary valvular stenosis and hypertrophic cardiomyopathy. Congenital polyvalvular disease (CPVD) refers to congenital dysplasia of two or more cardiac valves. We diagnosed a RASopathy in two individuals with CPVD and noted that CPVD in RASopathies has rarely been reported in the literature. Thus, we performed a retrospective chart review and literature review to investigate the association and characterize the phenotype of CPVD in the RASopathies. CPVD was present in 2.5% (<jats:italic>n<\/jats:italic> =\u20096\/243) of individuals in our RASopathy cohort. Involvement of two cardiac valves, commonly the aortic and pulmonic valves, was seen in the majority of individuals (6\/8; 75%) in our cohort, but only 27% (3\/11) of reported CPVD and RASopathy cases in the literature. CPVD should be considered an associated cardiovascular phenotype of the RASopathies, which has implications for diagnosis and management.<\/jats:p>","DOI":"10.1002\/ajmg.a.62146","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T10:10:57Z","timestamp":1615198257000},"page":"1486-1493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Congenital polyvalvular disease expands the cardiac phenotype of the <scp>RASopathies<\/scp>"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8616-7239","authenticated-orcid":false,"given":"Dena R.","family":"Matalon","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Stanford University  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Stanford University  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5748-3507","authenticated-orcid":false,"given":"Elizabeth J.","family":"Bhoj","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and Molecular Biology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avni B.","family":"Santani","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and Molecular Biology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth","family":"Keena","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and Molecular Biology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meryl S.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Division of Cardiology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1145-4572","authenticated-orcid":false,"given":"Angela E.","family":"Lin","sequence":"additional","affiliation":[{"name":"Medical Genetics MassGeneral Hospital for Children  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Sheppard","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and Molecular Biology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine H.","family":"Zackai","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and Molecular Biology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/chd.12400"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002460010169"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34132"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.169"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5273(97)02937-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1670"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.11.002"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00796828"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4103\/2321-449X.127977"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31861"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40377"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33857"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37739"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1511"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-00994-x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320140409"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(90)90644-5"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38353"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ppedcard.2005.04.008"},{"key":"e_1_2_9_21_1","first-page":"bcr201420724","article-title":"Prolapse of all cardiac valves in Noonan syndrome","volume":"2015","author":"Otikunta A. 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