Causes of human hereditary lymphedemas. Lymph transport can be impaired because of a hypoplastic initial lymphatic capillary network, because of abnormal coverage of lymphatic capillaries with basement membrane components and SMCs or because of a lack of or malfunctioning lymphatic valves. Defective lymphatic drainage leads to tissue fibrosis and fat deposition caused by the abnormal local chronic inflammatory response. Genes that are mutated in human hereditary lymphedema are indicated in blue next to the processes to which they are thought to be causally related. Mechanisms of the action of GJC2, PTPN14, and IKBKG are not fully understood.