Moreover, the loss of SEMA3A function by the specific inhibition of its interaction with NRP1 leads to impairment of lymphatic valve development [12], while variants in VEGFR3, a tyrosine kinase receptor important in the development and establishment of the lymphatic system, are known to cause Milroy disease, a form of primary lymphedema [38]. This evidence concerns the gene FLT4 and Milroy disease.