In-vitro studies have demonstrated that PIK3CA-mutant ECs generate pathological proliferative response only upon stimulation of growth signals [60, 68, 87], which corresponds with clinical observations where low-flow vascular malformations arise during embryonic development, expand proportionally with the patient’s physiological growth and remain largely quiescent during adulthood, when the production of growth factors is minimal. The gene discussed is PIK3CA; the disease is vascular malformation.