{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:41:44Z","timestamp":1773330104105,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,8,22]],"date-time":"2015-08-22T00:00:00Z","timestamp":1440201600000},"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":[[2015,12]]},"abstract":"<jats:sec><jats:label\/><jats:p>Noonan syndrome (NS) is a multiple malformation syndrome characterized by pulmonic stenosis, cardiomyopathy, short stature, lymphatic dysplasia, craniofacial anomalies, cryptorchidism, clotting disorders, and learning disabilities. Eight genes in the RAS\/MAPK signaling pathway are implicated in NS. Chronic pain is an uncommon feature. To investigate the prevalence of pain in NS, we distributed a two\u2010part questionnaire about pain among NS individuals at the Third International Meeting on Genetic Syndromes of the Ras\/MAPK Pathway. The first part of the questionnaire queried demographic information among all NS participants. The second part was completed by individuals with chronic pain. Questions included musculoskeletal problems and clinical features of pain. Forty\u2010five questionnaires were analyzed; 53% of subjects were female. Mean age was 17 (2\u201348) years; 47% had a <jats:italic>PTPN11<\/jats:italic> mutation. Sixty\u2010two percent (28\/45) of individuals with NS experienced chronic pain. There was a significant relationship between prevalence of pain and residing in a cold climate (<jats:italic>P<\/jats:italic>\u2009=\u20090.004). Pain occurred commonly in extremities\/joints and head\/trunk, but more commonly in extremities\/joints (<jats:italic>P<\/jats:italic>\u2009=\u20090.066). Subjects with hypermobile joints were more likely to have pain (<jats:italic>P<\/jats:italic>\u2009=\u20090.052). Human growth hormone treatment was not statistically significant among subjects without chronic pain (<jats:italic>P<\/jats:italic>\u2009=\u20090.607). We conclude that pain is a frequent and under\u2010recognized clinical feature of NS. Chronic pain may be associated with joint hypermobility and aggravated by colder climate. Our study is a preliminary investigation that should raise awareness about pain as a common symptom in children and adults with NS. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37337","type":"journal-article","created":{"date-parts":[[2015,8,22]],"date-time":"2015-08-22T13:06:08Z","timestamp":1440248768000},"page":"2998-3005","source":"Crossref","is-referenced-by-count":16,"title":["Chronic pain in Noonan Syndrome: A previously unreported but common symptom"],"prefix":"10.1002","volume":"167","author":[{"given":"Sravanthi","family":"Vegunta","sequence":"first","affiliation":[{"name":"University of Arizona College of Medicine Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Cotugno","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pain Management Phoenix Children's Hospital Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pain Management Phoenix Children's Hospital Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa A.","family":"Grebe","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism Phoenix Children's Hospital Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1754"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2013.04.009"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.44"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1987.67.1.67"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0995"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-010-0178-2"},{"key":"e_1_2_7_8_1","first-page":"998","article-title":"Symptom and joint mobility progression in the joint hypermobility syndrome (Ehlers\u2013Danlos syndrome, hypermobility type)","volume":"29","author":"Castori M","year":"2011","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36315"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.497"},{"key":"e_1_2_7_11_1","first-page":"129","article-title":"Pain assessment: Global use of the brief pain inventory","volume":"23","author":"Cleeland CS","year":"1994","journal-title":"Ann Acad Med Singapore"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182872e80"},{"key":"e_1_2_7_13_1","first-page":"710","article-title":"The prevalence of chronic widespread pain in the general population","volume":"20","author":"Croft P","year":"1993","journal-title":"J Rheumatol"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2012.02.012"},{"key":"e_1_2_7_15_1","first-page":"546","article-title":"Validity and reliability of the pain questionnaire \u201cbrief pain inventory\u201c. 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