Answer to CC #19

Case challenge #19 presented a 57 year old with HCV and years of recurrent epistaxis. He also noted generalized weakness, DOE, and chest pressure with exertion. His father also had recurrent nosebleeds. Exam reveals tachycardia and a flow murmur.  Endoscopy reveals the following:


What is the most likely diagnosis?


You’re right, its Rendu-Osler-Weber Syndrome, also known as Hereditary Hemorrhagic Telangiectasia!

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.

Although hemorrhage is usually the presenting symptom of mucosal telangiectases and cerebral AVMs, most visceral AVMs present as a consequence of blood shunting through the abnormal vessel and bypassing the capillary bed. Shunting of air, thrombi, and bacteria through PAVMs, thus bypassing the filtering capabilities of the lungs, may cause transient ischemic attacks, embolic stroke, and cerebral and other abscesses. Migraine headache, polycythemia, and hypoxemia with cyanosis and clubbing of the nails are other complications of PAVMs Hepatic AVMs can present as high-output heart failure, portal hypertension, or biliary disease.

Optimal medical management for HHT requires distinguishing between organ locations where telangiectases and AVMs are best managed symptomatically/expectantly, versus those in which lesions should be detected and treated before the onset of symptoms. International Clinical Management Guidelines for HHT were published as a result of a consensus conference.In general, telangiectases of the skin, oral and GI mucosa, and liver are treated when symptoms dictate, but AVMs of the lungs and brain are treated in patients without symptoms given their often sudden and catastrophic presentation. The HHT Foundation International ( lists HHT Centers in the United States and elsewhere, as well as information regarding current management for both patients and clinicians.

McDonald, J., Bayrak-Toydemir, P., Pyeritz, R.E. Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis. Genet. Med. 2011;13:607–616.