# Advances in genetics, signaling, and modeling of venous malformations

## TL;DR

This review discusses the genetic causes, signaling pathways, and models used to study venous malformations, aiming to improve treatments for this vascular condition.

## Contribution

The paper provides a comprehensive review of genetic, signaling, and modeling advances in venous malformations.

## Key findings

- Venous malformations are mainly caused by mutations in TIE2 or PIK3CA genes.
- Current treatments like sclerotherapy and mTOR inhibitors have limited long-term success.
- In vitro, 3D, and in vivo models are advancing VM research and therapy testing.

## Abstract

Vascular anomalies are defects resulting from the abnormal development or growth of the vasculature. Among these, venous malformations (VMs) are predominantly caused by mutations in the TIE2 or PIK3CA genes, which disrupt endothelial cell morphogenesis and vessel maturation. VM lesions are typically diagnosed during infancy or childhood and often persist and enlarge throughout adulthood, causing chronic complications such as pain, deformity, and coagulopathy. Despite available treatments such as sclerotherapy and mTOR inhibitors like sirolimus, achieving complete and long-term resolution of VMs remains a significant challenge. This review examines the genetic basis of VMs, explores the underlying molecular signaling mechanisms, and compares various experimental models—including in vitro, 3D, and in vivo systems—that have advanced our understanding of VM and provided platforms for testing potential therapies. Future research should prioritize the development of more precise and personalized models to drive improved strategies and better outcomes for patients with VMs.