PIK3CA-Related Overgrowth Spectrum (PROS)

Abstract

PIK3CA-related overgrowth spectrum (PROS) refers to a group of disorders of segmental overgrowth caused by mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). PROS is an umbrella term that includes several diagnostic entities, some of which were independently described prior to the discovery that PIK3CA mutations were common to all (Keppler-Noreuil et al, Am J Med Genet A 164A(7):1713–1733, 2014; Mirzaa et al, PIK3CA-related segmental overgrowth. In: Pagon et al (ed), GeneReviews® [Internet]. University of Washington, Seattle, pp 1993–2016, 2013). The mutations that cause PROS are typically, but not always, postzygotic, meaning that the mutation is not present in every cell in the body. The resulting mosaicism causes some of the phenotypic variation, although specific PIK3CA genotypes also contribute. The PROS diagnostic entities (Keppler-Noreuil et al, Am J Med Genet A 167A(2):287–295, 2015) include: Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal (CLOVES) syndrome Fibroadipose hyperplasia or overgrowth (FAO)/hemihyperplasia multiple lipomatosis (HHML) Klippel-Trenaunay syndrome (KTS) Megalencephaly-capillary malformation syndrome (MCAP syndrome) Hemimegalencephaly (HMEG) and dysplastic megalencephaly (DMEG) Isolated macrodactyly Isolated lymphatic malformations (LM) Facial infiltrating lipomatosis Focal cortical dysplasia (FCD)