Indeed, patients bearing heterozygous mutations affecting either Alk1 or Eng, or downstream Smad4, exhibit the congenital disease hereditary hemorrhagic telangiectasia (HHT), which is characterized by microvascular overgrowth and the focal appearance of large-caliber AVMs that lack clear arterial or venous identity60,65. The gene discussed is SMAD4; the disease is hereditary hemorrhagic telangiectasia.