Genetic Causes of Vascular Malformations and Common Signaling Pathways Involved in Their Formation

Abstract

The identification of the genetic cause of vascular malformations is improving understanding of pathogenesis of these lesions and also informing potential opportunities for treatment. Somatic activating mutations affecting RAS/MAPK and PIK3/AKT/mTor pathways are implicated in all types of vascular malformations. Pathogenic variants associated with vascular lesions may be germline or somatic. Next-generation sequencing technologies allow identification of lower level mosaic mutations than was achievable with standard Sanger sequencing. Best practice strategies to identify underlying genetic mutations in vascular malformations are influenced by the tissues involved and the type of vascular lesion.

Keywords: AVM; Capillary; Germline; Lymphatic; PI3K-AKT-mTOR; Somatic; Vascular; Venous.