In Down syndrome, the overexpression of genes located on chromosome 21—particularly those involved in angiogenesis inhibition, such as COL4A3, endostatin (COL18A1), and RCAN1—is known to contribute to vascular immaturity, pulmonary hypoplasia, and increased risk for pulmonary hypertension. Here, RCAN1 is linked to pulmonary arterial hypertension.