PIL is considered congenital in origin, most likely caused by failure in the proper formation of lymphatic vessels during infancy or earlier, and mutation or dysfunction of some genes or transcriptional factors, such as vascular endothelial growth factor-C, VEGFR3, prosperorelated homeobox-transcriptional factor, forkhead transcriptional factor and SOX18, have been reported to be related to lymphedematous diseases and lymphangiectasia [20–22]. This evidence concerns the gene SOX18 and lymphangiectasis.