PIK3CA-related overgrowth spectrum (PROS): new insight in known diseases

Abstract

The overgrowth syndromes related to phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) are grouped under the concept of PROS (PIK3CA-related overgrowth spectrum). It is a heterogeneous group of diseases, considered a rare disease (ORPHA: 530313), which combines the presence of vascular malformations with segmental overgrowth of some parts of the body. All these diseases are caused by mutations in the gene that encodes for the alpha subunit of PI3K. These mutations are somatic and take place during the embryonic stage. Depending on the stage of embryonic development and the affected germ layers, the phenotype will be very different, from syndromes with extensive involvement to isolated forms. Although there are clinical criteria, identification of the mutation by biopsy, although complex, confirms the diagnosis. The objective of the present study is to review the pathophysiological, clinical, diagnostic, and therapeutic aspects of PROS, in order to optimize its identification.

Keywords: Enfermedades minoritarias; Fosfatidilinositol-4,5-bifosfato 3-cinasa (PI3K); Malformaciones vasculares; PIK3CA-related overgrowth spectrum (PROS); Phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K); Rare diseases; Síndromes de sobrecrecimiento relacionados con PIK3CA (PROS); Vascular malformation.