ACVRL1 and hereditary hemorrhagic telangiectasia: The majority (>85%) of HHT patients are heterozygous for loss of function (LOF) mutations in the endoglin (ENG, HHT1) or activin A receptor like type 1 (ALK1, HHT2) genes (1, 2), whilst a minority (∼5%) carry mutations in the SMAD4 gene and show a combined juvenile polyposis and HHT phenotype (3).