Angiopoietin 2 is also required for button formation,5 and mutations in ANGPT2 have since been identified in congenital lymphedema patients.33 Interestingly, a recent study found that inhibition of angiopoietin 2 or deletion of the angiopoietin receptors, Tie1 and Tie2, decreased the expression of VEGFR3 in LECs.34 However, to our knowledge, lymphoscintigraphy was not performed on these patients, so it is unknown whether they fail to absorb interstitial tracer and thus if defective button formation contributes to this form of lymphedema. This evidence concerns the gene ANGPT2 and lymphedema.