Mutations in three different genes have been causally linked to HHT: (1) The ENG gene encoding the co-receptor endoglin causing HHT1 [85]; (2) the ACVRL1 gene encoding ALK1 causing HHT2 [86]; and (3) the SMAD4 gene causing a mixed syndrome consisting of both juvenile polyposis and HHT [87]. This evidence concerns the gene ACVRL1 and juvenile polyposis syndrome.