Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Rendu-Weber syndrome, is a genetic condition which affects the blood vessels. In HHT, there are abnormal connections between some blood vessels. HHT is characterized by one or more of the following:
About one in every 5,000 to 10,000 people have HHT. HHT is often under-diagnosed because people and doctors are not familiar with the symptoms.
HHT Symptoms & HHT Diagnosis
HHT is most often diagnosed when the AVMs begin causing symptoms. A clinical diagnosis of HHT can be made if someone is known to have three of the four common signs:
- Frequent nosebleeds
- Telangiectasias found on the mouth, lips, tongue, and fingertips
- Internal AVMs found in the lungs, brain, liver, and intestines
- A family history of HHT
Nosebleeds are caused by telangiectasias in the nose. Almost all people with HHT will develop frequent nosebleeds not linked with trauma. Nosebleeds can occur as often as several times a day but are often less frequent. It is common for the nosebleeds to occur overnight for no reason. The chance of having nosebleeds increases with age.
Telangiectasias are most common on the lips, tongue, mouth, and fingertips. They are also seen on the fingers, ears, face, and chest. People with HHT usually have several to many telangiectasias. The chance to develop telangiectasias increases with age.
Internal AVMs cannot be seen on physical exam by a doctor so people with HHT may not know they have any. Imaging such as CT scans, MRIs and bubble echos are often needed to identify internal AVMs. Some people with internal AVMs will have signs of the AVM without knowing they have one. For example, a person with a lung AVM may have problems breathing and increased fatigue.
HHT is caused by genetic changes in one of three genes (ACVRL1, ENG and SMAD4). Almost everyone with a clinical diagnosis of HHT will have a change in one of these genes. Three other genes have also recently been reported to be found with HHT-like features (GDF2, RASA1, and EPH4). Overall, about 10-15% of people with HHT will not be found to have a genetic change in any gene. Therefore, some people do have HHT, but it’s not possible to identify the genetic change causing them to have it.
HHT is a dominant condition. If you have HHT, you have a 50 percent chance of passing it on to each of your children. If genetic testing is performed and a change is found, your family members can be tested to find out if they also have HHT. Very rarely, HHT is not inherited from a parent. It may be new or “de novo” or it may be "mosaic". In these cases, other people in the family do not have HHT; but the person diagnosed with HHT still has a 50 percent chance of passing it on to each child.
Several complications are possible with HHT:
Brain AVM: About 20 percent of people with HHT will have a brain AVM. Brain AVMs can bleed, causing neurologic problems. Symptoms may include dizziness, headache, changes in vision, seizures and stroke.
Lung AVM: 15-50 percent of people with HHT will have a lung AVM. There is always a risk for rupture with this type of AVM. The risk increases during pregnancy. People with a lung AVM are also at risk for stroke or brain abscess. Other symptoms include migraines and chronic fatigue.
Liver AVM: 30-80 percent of people with HHT will have a liver AVM. Most people with liver AVMs are not treated because they don’t usually bleed or cause sudden medical problems. Rarely, later in life, liver or heart failure can occur.
Spinal AVM: Spinal AVMs are rare in HHT. They can cause pain and / or loss of feeling or function in an arm or a leg.
GI telangiectasia: About 80 percent of people with HHT have telangiectasias in their stomach and intestines; but only 20 percent develop bleeding, most often later in life. Signs of bleeding include blood in the stool (black or bloody stools) and anemia. Anemia can cause fatigue, shortness of breath, chest pain or lightheaded feelings.
Nasal telangiectasias: Nasal telangiectasias can result in nosebleeds. Ninety-five percent of people with HHT will develop frequent nosebleeds. The chance of nosebleeds increases with age. How often and how long nosebleeds occur vary person to person. Depending on the amount of blood lost, nosebleeds can also cause anemia.
Mucocutaneous telangiectasias (hands, face, lips, mouth): 95 percent of people with HHT have telangiectasias on their hands, face, lips, or inside their mouth. The chance of developing these increases with age. The telangiectasias can bleed but are less likely to bleed than those in the nose.
Treatment of AVMs
- Observe: Small AVMs are sometimes observed over time for any changes or growth.
- Surgical excision (removal): This technique is similar to other brain surgeries. The location of the AVM and the risks to removing it help your doctors decide if surgical excision or another treatment is the best option for you.
- Embolization: In this technique, a doctor inserts a catheter into an artery in your groin. It is then threaded through your arteries into the feeding artery of the AVM. A substance (ex: glue) is then inserted to block blood flow into the AVM.
- Stereotactic radiosurgery (SRS): Focused radiation is used to destroy the AVM.
- Observe: Small AVMs are sometimes observed over time to watch for any changes or growth.
- Embolization: In this technique, a doctor inserts a catheter into an artery in your groin. It is then threaded through your arteries into the feeding artery of the AVM. A substance (ex: coil) is then inserted to block blood flow into the AVM.
- Lobectomy: In this technique, the part of the lung that has the AVM is removed.
Treatment of Nosebleeds
- Use of a humidifier
- Use of a water-based nasal lubricant
- Possible uses of oral or topical medicines are being investigated
- Coagulation therapy (laser coagulation, cautery)
- Surgery (septal dermoplasty, Young’s procedure)
- Treatment of Anemia
- Oral iron
- IV iron replacement
- Red blood cell transfusions
- IV bevacizumab / avastin
Because HHT can affect many systems of the body, people need a whole team of doctors and health care workers to treat each body system.
The Cincinnati Children's HHT Center is made up of specialists from a wide variety of backgrounds who care for both children and adults with HHT. This includes:
- Hematology / Oncology
- Human Genetics
- Interventional Radiology
- Neurointerventional Radiology
- Social Work
Clinic is held two times per month at Cincinnati Children’s. The pediatric team works closely with adult specialists to provide complete care for patients of all ages. Patients receive diagnosis, including coordination of genetic testing, treatment, and management of HHT through the HHT Center.
Other resources to help parents and families find out more about HHT include:
- Cure HHT is a worldwide, non-profit group whose purpose is to support patients and families and educate medical professionals.
- The HHT International Clinical Guidelines were first published in 2009 and updated in 2020. They detail the diagnosis, treatment, screening and management recommended by consensus by international HHT experts.
- GeneTests is a medical genetics information resource.
- ClinicalTrials.gov is a registry and results database of clinical studies conducted around the world.