They cause lymphangiectasia through overactivation of the cell signaling pathway, such as phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) pathway and RAS-MEK, and the lymphangiectasia contacting the skeleton progressively lyses the bone and leads to bone loss. This evidence concerns the gene PIK3CA and lymphangiectasis.