{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:38:24Z","timestamp":1791041904067,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,11,19]],"date-time":"2012-11-19T00:00:00Z","timestamp":1353283200000},"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":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Noonan syndrome (NS) is a heterogeneous developmental disorder caused by missense mutations in genes involved in the Ras\/MAPK signaling pathway, a major mediator of early and late developmental processes. The diagnosis of NS is made on clinical grounds with molecular confirmation of a mutation found in 63% of cases. Key clinical features include short stature, cardiac defects, developmental delay, lymphatic dysplasias, bleeding tendency, and a constellation of distinctive facial features and physical exam findings. The prevalence of medical issues or the development of new ones in adults with NS is not well\u2010studied. This cross\u2010sectional study reports on the prevalence of clinical conditions and their ages of onset in a cohort of 35 adolescents and adults with NS aged 16\u201368 years old (mean age 28 years). In this cohort, 34 of 35 subjects (97%) had had full <jats:italic>PTPN11<\/jats:italic> sequencing; 37% were <jats:italic>PTPN11<\/jats:italic> positive, 23% were <jats:italic>SOS1<\/jats:italic> positive, and 3% were <jats:italic>BRAF<\/jats:italic> positive. Mean adult height in both men and women was at the 3rd\u201310th centile. The most prevalent clinical findings in this cohort included pulmonary valve stenosis (71%), easy bruising (63%), GERD (60%), constipation (51%), scoliosis (54%), chronic joint pain (54%), lymphedema (49%), depression (49%), anxiety (49%), Chiari malformation (20%), and osteopenia\/osteoporosis (14%). In summary, adults with NS are affected by multi\u2010organ morbidity and require special medical management aimed towards the most prevalent and serious known medical complications. Larger studies characterizing the clinical conditions found in NS adults are needed to provide potential genotype\u2013phenotype correlations that may aid in clinical management. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.35639","type":"journal-article","created":{"date-parts":[[2012,11,20]],"date-time":"2012-11-20T05:09:11Z","timestamp":1353388151000},"page":"3106-3111","source":"Crossref","is-referenced-by-count":89,"title":["Medical complications, clinical findings, and educational outcomes in adults with Noonan syndrome"],"prefix":"10.1002","volume":"158A","author":[{"given":"Patroula","family":"Smpokou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Tworog\u2010Dube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju S.","family":"Kucherlapati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,19]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"GeneReviews [Internet]","author":"Allanson J","year":"2011"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/NRL.0b013e31817833c4"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.12.004"},{"key":"e_1_2_6_5_1","first-page":"948","article-title":"Prevalence of self\u2010reported arthritis or chronic joint symptoms among adults\u2014United States, 2001","volume":"51","author":"CDC","year":"2002","journal-title":"MMWR"},{"key":"e_1_2_6_6_1","first-page":"61","article-title":"Type 1 Arnold\u2013Chiari malformation in a subject with Noonan syndrome","volume":"23","author":"Colli R","year":"2001","journal-title":"Pediatr Med Chir"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.425"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33045"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2008.543"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33391"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2006.11.130"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019605-200310000-00013"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.62.6.617"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.3171\/2011.8.PEDS11160"},{"key":"e_1_2_6_15_1","first-page":"308","volume-title":"Handbook of neurodevelopmental and genetic disorders in adults","author":"Noonan J","year":"2005"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20502"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2073"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.45.8.753"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/BPO.0b013e318220396e"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1926"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2006.104547"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01619.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng772"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000276766"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2003.09.013"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.126.8.1111"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30747"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.35639","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.35639","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T12:44:51Z","timestamp":1697633091000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.35639"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,19]]},"references-count":26,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["10.1002\/ajmg.a.35639"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.35639","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,19]]}}}