Hereditary hemorrhagic telangiectasia: An overview of diagnosis, management, and pathogenesis

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is a disorder of development of the vasculature characterized by telangiectases and arteriovenous malformations in specific locations. It is one of most common monogenic disorders, but affected individuals are frequently not diagnosed. The most common features of the disorder, nosebleeds, and telangiectases on the lips, hands, and oral mucosa are often quite subtle. Optimal management requires an understanding of the specific presentations of these vascular malformations, especially their locations and timing during life. Telangiectases in the nasal and gastrointestinal mucosa and brain arteriovenous malformations generally present with hemorrhage. However, complications of arteriovenous malformations in the lungs and liver are generally the consequence of blood shunting through these abnormal blood vessels, which lack a capillary bed and thus result in a direct artery-to-vein connection. Mutations in at least five genes are thought to result in hereditary hemorrhagic telangiectasia, but mutations in two genes (ENG and ACVRL1/ALK1) cause approximately 85% of cases. The frequency of arteriovenous malformations in particular organs and the occurrence of certain rare symptoms are dependent on the gene involved. Molecular genetic testing is used to establish the genetic subtype of hereditary hemorrhagic telangiectasia in a clinically affected individual and family, and for early diagnosis to allow for appropriate screening and preventive treatment. Genet Med 2011:13(7):607-616.