Arteriovenous Malformations (AVMs): Molecular Pathogenesis, Clinical Features, and Emerging Therapeutic Strategies

Arteriovenous malformations (AVMs) are fast-flow vascular malformations formed by direct artery-to-vein shunts without an intervening capillary bed, which increases the risk of hemorrhage and organ-specific damage. A synthesis of recent advances shows that AVMs arise from interplay between germline susceptibility (<i>ENG</i>, <i>ACVRL1</i>, <i>SMAD4</i>, <i>RASA1</i>, <i>EPHB4</i>), somatic mosaicism (<i>KRAS</i>, <i>MAP2K1</i>, <i>PIK3CA</i>), perturbed signaling (TGF-β/BMP, Notch, VEGF, PI3K/AKT, RAS/MAPK), hemodynamic stress, and inflammation. Multimodal imaging-digital subtraction angiography (DSA), MRI/MRA with perfusion and susceptibility sequences, CTA, Doppler ultrasound, and 3D rotational angiography-underpins diagnosis and risk stratification, while arterial spin labeling and 4D flow techniques refine hemodynamic assessment. Management is individualized and multidisciplinary, combining endovascular embolization, microsurgical resection, and stereotactic radiosurgery (SRS); a non-surgical approach and monitoring remain reasonable for some asymptomatic AVMs. Device and technique innovations (detachable-tip microcatheters, pressure-cooker approaches, and newer liquid embolics such as PHIL and Squid) have broadened candidacy, and precision-medicine strategies, including pathway-targeted pharmacotherapy, are emerging for syndromic and somatic-mutation-driven AVMs. Animal models and computational/radiomics tools increasingly guide hypothesis generation and treatment selection. We outline practical updates and future priorities: integrated genomic-imaging risk scores, genotype-informed medical therapy, rational hybrid sequencing, and long-term outcome standards focused on hemorrhage prevention and quality of life.