Hereditary Hemorrhagic Telangiectasia: A Review of Gene Targets and Emerging Therapies

Hereditary hemorrhagic telangiectasis (HHT), formerly called Osler-Weber-Rendu syndrome, is a rare autosomal-dominant vascular disorder characterized by mucocutaneous and visceral telangiectasis involving multiple organ systems, such as skin, liver, brain, and lung. While recurrent epistaxis is the most common and widely studied complication, visceral arteriovenous malformations (AVMs), such as pulmonary and hepatic, pose more serious complications yet remain under-recognized. These AVMs can lead to life-threatening complications, such as paradoxical emboli, stroke, significant gastrointestinal bleeds, and high-output heart failure, especially in the setting of hepatic AVMs. Despite its first description by Henri Rendu over a century ago, no food and drug administration (FDA)-approved drugs currently exist for HHT. This review provides a comprehensive review of HHT, covering the historical background, epidemiology, genetic and molecular pathophysiology, organ-specific involvement, emerging therapies, and current clinical guidelines. We highlight cardiovascular manifestations, existing treatments, and their limitations. Finally, this review aims to explore emerging therapeutic targets and investigational drugs that may offer future promise in the management of HHT, with particular emphasis on pomalidomide, a novel oral agent that has the potential to be a true game-changer in expanding the treatment options for HHT.