Clinical characteristics of pulmonary arterial hypertension associated with Down syndrome

The genetic abnormalities associated with Down syndrome (DS) are still being identified. Few studies have examined the roles of CRELD1 and GATA4 in cardiac abnormalities or their association with pulmonary artery histopathology. Children with DS have an elevated risk of pulmonary arterial hypertension (PAH). 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-to-right 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 DS, but endothelin-1 and thromboxane are elevated. Perioperatively, patients with DS may experience pulmonary hypertensive crisis after intracardiac repair and prolonged PAH, and have a poorer response to nitric oxide inhalation. To better manage DS, it is crucial to systematically evaluate the systemic complications of DS. 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 DS, except among patients with a complete atrioventricular canal defect.