PROS Overview

PIK3CA-Related Overgrowth Spectrum (PROS) 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 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.¹

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

• SKIN LESIONS

Overgrowths are not always overt. Vascular malformations, for example, may not be externally apparent. Nonetheless, they represent a significant medical concern.¹ Click here to learn more about common PROS features.

Hear from PROS experts

Learn from medical expert, Dr Kiersten W. Ricci, as she delves further under the PROS umbrella, explaining common PROS disorders and PROS diagnosis.

Hear from leading expert, Dr Matthew Greives, as he discusses PROS, including diagnosis and the management landscape.

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).

References:

1. 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.
2. Cohen MM Jr. A comprehensive and critical assessment of overgrowth and overgrowth syndromes. Adv Hum Genet. 1989;18:181-303, 373-376.
3. 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.
4. Data on file. Novartis Pharmaceuticals Corp; 2020.