SMAD4 and hereditary hemorrhagic telangiectasia: Thus, heterozygous for mutations in the ENG (endoglin), ACVRL1 (activin receptor-like kinase 1; ALK1), GDF2 (BMP9) or SMAD4 genes results in different variants of the familial vascular disorder known as hereditary hemorrhagic telangiectasia (HHT) characterized by an abnormal angiogenesis process where boundaries between arteries and veins are not well established [3, 4].