SMAD4 and hereditary hemorrhagic telangiectasia: Hereditary hemorrhagic telangiectasia (HHT) results from a single mutation in a causative gene such as endoglin, ACVRL1 (encoding ALK-1), or SMAD4. The hallmark of HHT is the presence of arteriovenous malformations (AVMs), and smaller telangiectatic vessels.