PROS (PIK3CA-Related Overgrowth Spectrum) is a broad-ranging spectrum of disorders caused by PIK3CA mutations1
“Overgrowth disorders” refers to the broad range of medical conditions characterized by excess tissue growth.2,3 A number of these overgrowth disorders are now understood to share a single cause: somatic mutations of the PIK3CA gene.1
The classification “PROS”—PIK3CA-Related Overgrowth Spectrum—was proposed during a workshop at the National Institutes of Health in 2013 to unite this group of overgrowth disorders with one term that reflects their shared genomic cause.1*
*The term "PROS" was proposed at a 2-day workshop that included several researchers who have been studying this group of disorders and 3 parent representatives of patient-family support and advocacy organizations for individuals with these conditions. These criteria may change as research develops.
Clinical presentation of PROS
In addition to the presence of a PIK3CA mutation, PROS disorders have clinical commonalities.1
However, the clinical presentation of PROS is highly variable with respect to the extent, tissue specificity or pleiotropism, tissue types, affected organs, and anatomical locations of the overgrowths.1
PROS features broadly include1:
OVERGROWTH of adipose, muscle, nerve, or skeletal tissue
VASCULAR MALFORMATION, including capillary, venous, arteriovenous, or lymphatic effects
Overgrowths are not always overt. Vascular malformations, for example, may not be externally apparent. Nonetheless, they represent a significant medical concern.1
Prevalence of PROS
Although reported rates of individual PROS disorders are low or unknown, the spectrum collectively could represent a more significant patient number, with an estimated prevalence of 14 people per million.4†
†The estimated prevalence is based on available information for the following 5 disorders: Klippel-Trenaunay syndrome (KTS); congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal (CLOVES syndrome); megalencephaly-capillary malformation (MCAP or M-CM); hemihyperplasia-multiple lipomatosis (HHML); and fibroadipose hyperplasia or overgrowth (FAO).
- Keppler-Noreuil KM, Rios JJ, Parker VER, et al. PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. Am J Med Genet A. 2015;167A(2):287-295.
- Cohen MM Jr. A comprehensive and critical assessment of overgrowth and overgrowth syndromes. Adv Hum Genet. 1989;18:181-303, 373-376.
- Keppler-Noreuil KM, Sapp JC, Lindhurst MJ, et al. Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum. Am J Med Genet A. 2014;164A(7):1713-1733.
- Data on file. Novartis Pharmaceuticals Corp; 2020.