Overview
Clinical Meaning
Hereditary hemorrhagic telangiectasia (HHT, Osler Weber Rendu syndrome) is an autosomal dominant vascular disorder affecting 1 in 5,000 8,000 people, caused by mutations in gene...
Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu syndrome) is an autosomal dominant vascular disorder affecting 1 in 5,000-8,000 people, caused by mutations in genes encoding components of the TGF-beta/BMP signaling pathway essential for vascular development. HHT1 (ENG gene — endoglin) and HHT2 (ACVRL1 gene — activin receptor-like kinase 1/ALK1) account for >85% of cases. These mutations impair endothelial cell signaling, leading to abnormal angiogenesis with formation of fragile, dilated vessels lacking normal capillary structure. Telangiectasias are small mucocutaneous arteriovenous malformations (AVMs) consisting of direct arteriole-to-venule connections without intervening capillary bed, covered only by a thin endothelial layer without supporting smooth muscle or elastic fibers. They are extremely fragile and prone to hemorrhage from minor trauma. Telangiectasias appear as small red spots on the lips, tongue, nasal mucosa, fingertips, and GI tract. Larger arteriovenous malformations (AVMs) develop in the lungs (pulmonary AVMs — 30-50% of HHT patients), liver (hepatic AVMs — 30-70%), brain (cerebral AVMs — 10-23%), and spinal cord. Pulmonary AVMs allow right-to-left shunting of blood bypassing the pulmonary capillary filter, causing paradoxical embolization (brain abscess from septic emboli, stroke from paradoxical...