For example, delayed onset lymphedema is often characteristic of patients with lymphedema distichiasis,69 in which FOXC2 haplodeficiency leads to a reduction in the number and competency of lymphatic valves.61,70,71 Likewise, the onset of overt lower limb lymphedema is not obvious in many CS subjects until the teenage years.6 Whether that delay is related to puberty, age and/or repetitive exposure to gravitational loads—or other factors—remains to be investigated. The gene discussed is FOXC2; the disease is Cowden syndrome 1.