Hereditary hemorrhagic telangiectasia is a disorder that results in the development of multiple abnormalities in the blood vessels.

In the circulatory system, blood carrying oxygen from the lungs is normally pumped by the heart into the arteries at high pressure. The pressure allows the blood to make its way through the arteries to the smaller vessels (arterioles and capillaries) that supply oxygen to the body's tissues. By the time blood reaches the capillaries, the pressure is much lower. The blood then proceeds from the capillaries into veins, through which it eventually returns to the heart.

In hereditary hemorrhagic telangiectasia, some arterial vessels flow directly into veins rather than into the capillaries. These abnormalities are called arteriovenous malformations. When they occur in vessels near the surface of the skin, where they are visible as red markings, they are known as telangiectases (the singular is telangiectasia).

Without the normal buffer of the capillaries, the blood moves from the arteries at high pressure into the thinner walled, less elastic veins. The extra pressure tends to strain and enlarge these blood vessels, and may result in compression or irritation of adjacent tissues and frequent episodes of severe bleeding (hemorrhage). Nosebleeds are very common in people with hereditary hemorrhagic telangiectasia, and more serious problems may arise from hemorrhages in the brain, liver, lungs, or other organs.

There are several forms of hereditary hemorrhagic telangiectasia, distinguished mainly by their genetic cause but with some differences in patterns of signs and symptoms. People with type 1 tend to develop symptoms earlier than those with type 2, and are more likely to have blood vessel malformations in the lungs and brain. Type 2 and type 3 may be associated with a higher risk of liver involvement. Women are more likely than men to develop blood vessel malformations in the lungs with type 1, and are also at higher risk of liver involvement with both type 1 and type 2. Individuals with any form of hereditary hemorrhagic telangiectasia, however, can have any of these problems.

Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is a condition that involves both arteriovenous malformations and a tendency to develop growths (polyps) in the gastrointestinal tract. Hereditary hemorrhagic telangiectasia types 1, 2 and 3 do not appear to increase the likelihood of such polyps.

The incidence of hereditary hemorrhagic telangiectasia is difficult to determine because the severity of symptoms can vary widely and some symptoms, such as frequent nosebleeds, are common in the general population. In addition, arteriovenous malformations may be associated with other medical conditions. Hereditary hemorrhagic telangiectasia is widely distributed, occurring in many ethnic groups around the world. It is believed to affect between 1 in 5,000 and 1 in 10,000 people.

Mutations in several genes, including the ACVRL1, ENG, and SMAD4 genes, cause hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia type 1 is caused by mutations in the ENG gene. Type 2 is caused by mutations in the ACVRL1 gene. Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is caused by mutations in the SMAD4 gene. All these genes provide instructions for making proteins that are found in the lining of the blood vessels. These proteins interact with growth factors that control blood vessel development. Mutations in other genes, some of which have not been identified, account for other forms of hereditary hemorrhagic telangiectasia.

Mutations in these genes generally prevent the production of the associated protein or result in the production of a defective protein that cannot fulfill its function. An individual with a mutated gene will therefore have a reduced amount of the functional protein available in the tissue lining the blood vessels. This shortage is believed to result in the signs and symptoms of hereditary hemorrhagic telangiectasia.

Genetic Testing Information

• Genetic Testing Registry: Telangiectasia, hereditary hemorrhagic, type 1
• Genetic Testing Registry: Hereditary hemorrhagic telangiectasia type 3
• Genetic Testing Registry: Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
• Genetic Testing Registry: Telangiectasia, hereditary hemorrhagic, type 2

Genetic and Rare Diseases Information Center

• Hereditary hemorrhagic telangiectasia

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• TELANGIECTASIA, HEREDITARY HEMORRHAGIC, TYPE 2; HHT2
• JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME; JPHT
• TELANGIECTASIA, HEREDITARY HEMORRHAGIC, TYPE 1; HHT1
• TELANGIECTASIA, HEREDITARY HEMORRHAGIC, TYPE 4; HHT4

Scientific Articles on PubMed

• PubMed

• Brady AP, Murphy MM, O'Connor TM. Hereditary haemorrhagic telangiectasia: a cause of preventable morbidity and mortality. Ir J Med Sci. 2009 Jun;178(2):135-46. doi: 10.1007/s11845-008-0220-5. Epub 2008 Oct 16. Citation on PubMed
• Dupuis-Girod S, Bailly S, Plauchu H. Hereditary hemorrhagic telangiectasia: from molecular biology to patient care. J Thromb Haemost. 2010 Jul;8(7):1447-56. doi: 10.1111/j.1538-7836.2010.03860.x. Epub 2010 Mar 19. Citation on PubMed
• Govani FS, Shovlin CL. Hereditary haemorrhagic telangiectasia: a clinical and scientific review. Eur J Hum Genet. 2009 Jul;17(7):860-71. doi: 10.1038/ejhg.2009.35. Epub 2009 Apr 1. Citation on PubMed or Free article on PubMed Central
• Grand'Maison A. Hereditary hemorrhagic telangiectasia. CMAJ. 2009 Apr 14;180(8):833-5. doi: 10.1503/cmaj.081739. No abstract available. Citation on PubMed or Free article on PubMed Central
• McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis. Genet Med. 2011 Jul;13(7):607-16. doi: 10.1097/GIM.0b013e3182136d32. Citation on PubMed
• McDonald J, Wooderchak-Donahue W, VanSant Webb C, Whitehead K, Stevenson DA, Bayrak-Toydemir P. Hereditary hemorrhagic telangiectasia: genetics and molecular diagnostics in a new era. Front Genet. 2015 Jan 26;6:1. doi: 10.3389/fgene.2015.00001. eCollection 2015. Citation on PubMed or Free article on PubMed Central
• Ragsdale JA. Hereditary hemorrhagic telangiectasia: from epistaxis to life-threatening GI bleeding. Gastroenterol Nurs. 2007 Jul-Aug;30(4):293-9; quiz 300-1. doi: 10.1097/01.SGA.0000287202.36602.fb. Citation on PubMed
• Rimmer J, Lund VJ. Hereditary haemorrhagic telangiectasia. Rhinology. 2015 Sep;53(3):195-203. doi: 10.4193/Rhino14.274. Citation on PubMed
• Robert F, Desroches-Castan A, Bailly S, Dupuis-Girod S, Feige JJ. Future treatments for hereditary hemorrhagic telangiectasia. Orphanet J Rare Dis. 2020 Jan 7;15(1):4. doi: 10.1186/s13023-019-1281-4. Citation on PubMed or Free article on PubMed Central
• Sharathkumar AA, Shapiro A. Hereditary haemorrhagic telangiectasia. Haemophilia. 2008 Nov;14(6):1269-80. doi: 10.1111/j.1365-2516.2008.01774.x. Citation on PubMed
• Shovlin CL. Hereditary haemorrhagic telangiectasia: pathophysiology, diagnosis and treatment. Blood Rev. 2010 Nov;24(6):203-19. doi: 10.1016/j.blre.2010.07.001. Epub 2010 Sep 25. Citation on PubMed