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Few studies have examined the roles of <jats:styled-content style=\"fixed-case\">CRELD1<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">GATA4<\/jats:styled-content> in cardiac abnormalities or their association with pulmonary artery histopathology. Children with <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> have an elevated risk of pulmonary arterial hypertension (<jats:styled-content style=\"fixed-case\">PAH<\/jats:styled-content>). This increased risk is likely mainly due to genetic background, the structural characteristics of the pulmonary vascular wall, and certain heart diseases and partly due to pulmonary hypoplasia, upper and lower airway obstructive diseases, chronic infection, and neuromuscular underdevelopment. Exposure to increased left\u2010to\u2010right shunt flow increases sheer stress on endothelium and may induce endothelial dysfunction followed by irreversible remodeling of pulmonary arteries. Pathologic changes include endothelial cell proliferation and thickening of the pulmonary arterial wall due to mechanical responses to the thinner medial smooth muscle cell layer, which includes underdevelopment of alveoli. Production of prostacyclin and nitric oxide is diminished in <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>, but endothelin\u20101 and thromboxane are elevated. Perioperatively, patients with <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> may experience pulmonary hypertensive crisis after intracardiac repair and prolonged <jats:styled-content style=\"fixed-case\">PAH<\/jats:styled-content>, and have a poorer response to nitric oxide inhalation. To better manage <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>, it is crucial to systematically evaluate the systemic complications of <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>. Cardiac catheterization data, particularly those regarding pulmonary arterial resistance, are essential in assessing severity and response to vasodilating agents, preventing postoperative crisis, and evaluating the possibility of intracardiac repair. Advanced therapy with pulmonary vasodilating agents appears effective. Operative risk is similar for individuals with and without <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>, except among patients with a complete atrioventricular canal defect.<\/jats:p>","DOI":"10.1111\/ped.12349","type":"journal-article","created":{"date-parts":[[2014,4,2]],"date-time":"2014-04-02T07:32:48Z","timestamp":1396423968000},"page":"297-303","source":"Crossref","is-referenced-by-count":58,"title":["Clinical characteristics of pulmonary arterial hypertension associated with <scp>D<\/scp>own syndrome"],"prefix":"10.1111","volume":"56","author":[{"given":"Tsutomu","family":"Saji","sequence":"first","affiliation":[{"name":"Department of Pediatrics Pediatric Medical Center Toho University Omori Medical Center  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,3]]},"reference":[{"key":"e_1_2_3_2_1","volume-title":"Idiocy: And its Treatment by the Physiological Method","author":"Seguin E","year":"1866"},{"key":"e_1_2_3_3_1","first-page":"259","article-title":"Observations on an ethnic classification of idiots","volume":"3","author":"Down JLH","year":"1866","journal-title":"Clin. 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