Molecular Genetics and Vascular Anomalies

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, including congenital lipomatous overgrowth (CLOVES), fibroadipose hyperplasia (FAH), Klippel-Trenaunay Syndrome (KTS), isolated low flow vascular malformations (e.g. lymphatic and venous malformations), megalencephaly syndromes and focal cortical dysplasias, among others. Although many of these disorders are clinically distinct, there is a great deal of overlap, leading to the utility of considering them a spectrum of disorders due to post-zygotic activating mutations in the gene PIK3CA. In this chapter we review the phenotypic spectrum of these disorders, their clinical and molecular diagnosis, as well as their pathophysiology and management.