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We conducted clinical, pathological and molecular analyses of 146 patients with an\n                    <jats:italic>HRAS<\/jats:italic>\n                    mutation including 61 enrolled in an ongoing longitudinal study and 85 from the literature. In our study, the most common (84%)\n                    <jats:italic>HRAS<\/jats:italic>\n                    mutation was p.G12S. A congenital heart defect (CHD) was present in 27 of 61 patients (44%), usually non\u2010progressive valvar pulmonary stenosis. Hypertrophic cardiomyopathy (HCM), typically subaortic septal hypertrophy, was noted in 37 (61%), and 5 also had a CHD (14% of those with HCM). HCM was chronic or progressive in 14 (37%), stabilized in 10 (27%), and resolved in 5 (15%) patients with HCM; follow\u2010up data was not available in 8 (22%). Atrial tachycardia occurred in 29 (48%). Valvar pulmonary stenosis rarely progressed and atrial septal defect was uncommon. Among those with HCM, the likelihood of progressing or remaining stable was similar (37%, 41% respectively). The observation of myocardial fiber disarray in 7 of 10 (70%) genotyped specimens with Costello syndrome is consistent with sarcomeric dysfunction. Multifocal atrial tachycardia may be distinctive for Costello syndrome. Potentially serious atrial tachycardia may present in the fetus, and may continue or worsen in about one\u2010fourth of those with arrhythmia, but is generally self\u2010limited in the remaining three\u2010fourths of patients. Physicians should be aware of the potential for rapid development of severe HCM in infants with Costello syndrome, and the need for cardiovascular surveillance into adulthood as the natural history continues to be delineated. \u00a9 2011 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.33857","type":"journal-article","created":{"date-parts":[[2011,2,23]],"date-time":"2011-02-23T16:47:37Z","timestamp":1298479657000},"page":"486-507","source":"Crossref","is-referenced-by-count":120,"title":["Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: A Ras\/MAPK pathway syndrome"],"prefix":"10.1002","volume":"155","author":[{"given":"Angela E.","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Colan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronwyn","family":"Kerr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Rauen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Noonan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Baffa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Hopkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Sol\u2010Church","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Limongelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Christina","family":"Digilio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Marino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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