FLT4 is a one of the most well-known genetic drivers of primary lymphedema and will be discussed in-depth below in the context of CKM syndrome, but other targets that are causative for primary lymphedema include VEGFC, forkhead box protein C2 (FOXC2), angiopoietin-2 (ANGPT2), cadherin EGF LAG seven-pass G-type receptor 1 (CELSR1), and many others that lead to lymphatic valve dysfunction or defective lymphatic endothelial proliferation and survival (109–113). This evidence concerns the gene ANGPT2 and primary lymphedema.