This term was introduced by Biesecker in 2014 to refer to a range of conditions characterized by overgrowth of tissues associated with somatic pathogenic variants in the gene PIK3CA. ‘PROS’ has sometimes been used as an inclusive term for all proliferative lesions in which a pathogenic variant in the PIK3CA gene is detected (in which case LM would be considered a type of PROS), but the term is more properly used to describe conditions in which ‘overgrowth’ as defined in this glossary (i.e. growth involving more than one tissue type) is a feature. the list overgrowth disorders caused by PIK3CA somatic mutations has expanded to encompass lymphatic malformation, Klippel-Trenaunay syndrome (KTS), CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal), FAVA (fibrodipose vascular anomaly), megalencephaly-capillary malformation (MCAP or M-CM ), facial infiltrating lipomatosis, regional overgrowth (such as macrodactyly), CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry of the face and limbs, and partial or generalized overgrowth) and cutaneous lesions (seborrheic There are also some patients who have overgrowth in tissues in association with a gain of function pathogenic variant in PIK3CA, who do not fit any recognized pattern, in which case ‘PROS’ or ‘PROS (unspecified)’ may be used as a diagnostic label.