In 90% of patients with a definite clinical diagnosis of HHT, a mutation is identified in one of these three 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) [4]. The gene discussed is SMAD4; the disease is hereditary hemorrhagic telangiectasia.