ANGPT1 and Venous malformation: Somatic and constitutional variants in the TIE2-encoding gene TEK cause venous malformations via a gain-of-function mechanism,37–39 while constitutional LOF variants may underlie primary congenital glaucoma.40ANGPT1 variants are reported in primary congenital glaucoma41 and hereditary angio-oedema.42 Homozygous LOF of ANGPT1 and TEK is expected to be embryonically lethal in humans, as in mice, due to defective blood vessel formation,43 44 but not expected to cause fetal hydrops.