Molecular changes associated with vascular malformations

Abstract

Vascular anomalies are typically classified into two major categories, vascular tumors and vascular malformations. Most vascular malformations are caused sporadically by somatic mosaic gene mutations, and genetic analyses have advanced our understanding of the biomolecular mechanisms involved in their pathogenesis. Culprit gene mutations typically involve two major signaling pathways; the RAS/MAPK/ERK pathway is typically involved in fast-flow arteriovenous malformations, whereas the PI3K/AKT/mTOR pathway is typically mutated in slow-flow venous and lymphatic malformations. These findings suggest new therapeutic approaches to vascular malformations, focusing on targeting the etiologic mutated pathways. This review summarizes the currently available literature reflecting the updated International Society for Study of Vascular Anomalies classification system with emphasis on potential therapeutic targets that will provide vascular surgeons with an updated perspective on the etiologic basis of vascular malformations, allowing improved multidisciplinary collaboration.

Keywords: Congenital disorders; Rapamycin; Vascular anomaly; Vascular malformation; mTOR pathway.