FLT4 and lymphatic malformation 1: VEGFR3 missense mutations in the tyrosine kinase domains underlie the etiology of 70% cases of primary congenital lymphedema, known as Milroy disease (Karkkainen et al., 2000; Connell et al., 2009), indicating that the VEGFR3 signaling is important for the normal development of human lymphatic vasculature.