In the literature has been described that overexpression of anti-angiogenic genes located on chromosome 21—such as COL4A3, endostatin, and RCAN1—is implicated in impaired vascular development and pulmonary hypoplasia, thereby increasing the risk of pulmonary hypertension in DS patients [20,21,22,23,24,25,26,27]. This evidence concerns the gene COL4A3 and pulmonary arterial hypertension.