SMAD4 and hereditary hemorrhagic telangiectasia: In 96% of patients with a definite clinical diagnosis of HHT, a mutation is identified in one of these 3 genes: endoglin (ENG, HHT type 1), activin receptor-like kinase-1 (ACVRL1, HHT type 2), and Mothers against decapentaplegic homolog 4 (SMAD4, juvenile polyposis–HHT overlap syndrome) [2].