About HHT

Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. Before Dr. Rendu's work, doctors did not understand that individuals with what we now call HHT have abnormalities of their blood vessels, not a clotting problem in the blood itself. Drs. Weber and Osler reported on additional features of HHT in the early 1900s. More than a hundred years later, HHT is still often misdiagnosed in affected individuals and many doctors do not understand all of its manifestations.

What is HHT?

HHT is a hereditary disorder (passed down through generations) that is characterized by abnormal blood vessels. Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein.

A person with HHT has a tendency to form blood vessels that lack normal capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and bleed. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya) if it involves small blood vessels. The telangiectasias most commonly occur on the skin of the face and hands and the lining of the nose and mouth. The telangiectasias on the lining of the nose cause recurrent nosebleeds, the most common symptom of HHT. Telangiectasias can also occur in the digestive tract, particularly in the stomach and small bowel. There are a number of different treatments available for bleeding from telangiectasias in the nose and digestive tract.

An abnormality that involves a larger blood vessel is called an arteriovenous malformation (AVM). Some people with HHT will also have AVMs in one or more organs. AVMs occurring in the lungs and brain and can lead to serious complications. Everyone with HHT should undergo screening for lung and brain AVMs because if these are detected, they can be treated. The HHT Foundation recommends that all patients and families with HHT be assessed at an HHT Treatment Center for proper screening and treatment.

What causes HHT?

HHT is caused by a change (a “mutation”) in one of several HHT-associated genes. Changes in one of two of the genes, endoglin (ENG) and activin receptor-like kinase 1 (ACVRL1) are responsible for most cases of HHT. Changes in another gene, SMAD-related protein 4 (SMAD4), cause a combined syndrome of juvenile polyps of the gastrointestinal tract and HHT. At least two other unidentified genes also appear to cause HHT in a smaller number of individuals. There are hundreds of different mutations in each of the three known genes that can cause HHT. Having a mutation in an HHT-associated gene causes some blood vessels to form improperly leading to symptoms of HHT.

How is HHT inherited?

Each child born to an HHT parent has a 50% chance of inheriting the HHT gene mutation. One copy of each gene is inherited from the father and the other copy from the mother. People with HHT have one normal copy of the HHT gene and one mutated copy. When a person with HHT has a child, he or she will either pass on the normal copy of the gene, or the copy with the mutation. A child who inherits the gene with the mutation will have HHT. A child who inherits the normal copy of the gene will not have inherited HHT. Therefore, each time a person with HHT has a child, there is a 1 in 2 chance (50%) that the child will have HHT.

Nearly everyone with HHT will have inherited the disorder from a parent who also has HHT. In rare cases, a change in an HHT gene occurs in only an egg or sperm cell of someone who does not have HHT themselves. In these cases, the resulting child will have HHT, although the parents are unaffected.

Is there a test for HHT?

Yes, a person can be diagnosed with HHT through clinical examination or genetic testing. Genetic testing consists of analyzing DNA (the genetic material carried in cells) of the HHT-associated genes in a laboratory. Genetic testing is usually done on a small sample of blood, but can be done on a sample of saliva in certain cases. In a given family, genetic testing should start with someone who clearly has HHT.

Three different kinds of genetic tests for HHT are available. “Sequencing” of the genes involves looking at the precise sequence of building blocks in the sample of DNA to see if there is any abnormality. “Deletion and duplication” testing looks to see if there is a piece of the gene that is missing or duplicated. Single mutation analysis (often referred to as targeted sequencing) looks to see if one particular mutation that was previously identified in another family member is present or absent. More information about genetic testing for HHT is available in the "Manage HHT" tab of the website.

Can HHT be treated?

Yes. Although there is not yet a way to prevent the telangiectasias or AVMs from occurring, most can be treated once they occur. They should be treated if they are either causing a significant problem (as in the case of frequent nosebleeds) or if they have a high risk to cause a problem (such as a stroke from a Pulmonary AVM or Cerebral (brain) AVM). The current recommended treatment for a telangiectasia or AVM depends on both its size and location in the body. For specific information, please review the information in the "Manage HHT" tab of the website.

How can I get help or more information?

The HHT Foundation International, with its mission of patient/doctor education and funding research, provides multiple sources of information about HHT. Patient and Family Conferences are held each year - medical experts in the HHT community educate patients and physicians how to manage and treat this disease. A newsletter is published three times per year, providing the most current information about HHT. Membership entitles you to receive information about meetings as well as a subscription to the newsletter. Membership also allows you an opportunity to support the HHT Foundation's important work to improve care and eventually find a cure for HHT. Providing patient support  and resources is the central focus of our mission; you can contact the HHT Foundation at [email protected] or at 410-357-9932.