What is hereditary hemorrhagic telangiectasia?
Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare genetic disorder that affects blood vessels throughout the body. It’s characterized by the formation of abnormal blood vessels, called telangiectases, which are fragile and prone to bleeding.
HHT can affect various organs, including the nose, lungs, brain, and gastrointestinal tract. It can cause a range of symptoms, from frequent nosebleeds to life-threatening complications. It is important to understand the causes, symptoms, and available treatment options for HHT to manage this condition effectively.
Penn Medicine’s Hereditary Hemorrhagic Telangiectasia (HHT) Program provides coordinated care for this rare blood vessel disorder. Our specialists care for more than 200 people with HHT each year and are recognized as a Cure HHT Center of Excellence for our expertise, collaborative care, and research.
How HHT affects blood vessels
In the normal circulatory system, arteries take oxygenated blood from the heart and push it out to all parts of the body under high pressure, while veins return the blood back to the heart. Small capillaries typically connect the arteries to the veins. A person with HHT lacks capillaries in a few blood vessels in critical locations resulting in arteries that connect directly into veins. This creates a fragile vessel (telangiectasia) that can bleed or cause other problems.
Abnormal blood vessels in HHT are called:
- Telangiectases if they involve small blood vessels (nose, stomach, and intestine)
- Arteriovenous malformations (AVMs) if they involve a larger blood vessel (lung, brain, and liver)
What are the symptoms of HHT?
The symptoms of HHT depend on where abnormal blood vessels develop. Some people have mild symptoms, while others develop more serious complications.
The most common symptom of HHT is nosebleeds, affecting about 90 percent of people with HHT. These can happen daily and often first occur in childhood.
Those with abnormal GI tract blood vessels should watch for dark stools or blood in the stool. Nosebleeds and bleeding into the intestine can cause severe anemia, resulting in fatigue, shortness of breath, chest pain, and light-headedness.
People with AVMs in the lung (called pulmonary AVMs or PAVMs) may be short of breath at rest or with exercise. They may develop stroke or transient ischemic attack (TIA), heart attack, or an unusual infection, like a brain abscess. Rarely, PAVMs can rupture and cause bleeding in the chest (especially during pregnancy) or coughing up blood.
Heart failure is another risk for people with high-flow liver AVMs (also called hepatic AVMs or HAVMs). They can also develop liver or bile duct problems.
Hormonal changes, HHT, and pregnancy
Hormonal changes are known to affect bleeding from abnormal blood vessels caused by HHT. For some people, nosebleeds vary through the menstrual cycle and worsen after menopause. Most pregnant people with HHT can expect no serious HHT-related complications, although they will generally be classified as high-risk. For some, new skin telangiectases are detected, while others report improvements.
Hereditary hemorrhagic telangiectasia causes
In the mid-1990s, scientists discovered that an abnormal gene on either chromosome 9 or 12 causes HHT.
Genes on chromosome 9 (endoglin, HHT-1) and chromosome 12 (activin-like kinase, HHT-2) help regulate blood vessel formation. There are at least three other abnormal genes that can cause HHT.
HHT is a “dominant” disorder since one abnormal copy of the gene from one parent can cause the disorder. Although there is a 50 percent chance of inheriting this abnormal gene, children who do not have it cannot pass on the disease.
How is HHT diagnosed?
Hereditary hemorrhagic telangiectasia can be diagnosed through genetic testing of a gene mutation or by using clinical criteria based on the signs and history of symptoms.
Penn Medicine's hematology specialists provide genetic testing and diagnosis for HHT. Genetic testing can be beneficial in screening large families, particularly family members with no signs or symptoms of HHT.
Diagnosis can be made if a person has three or more of the following criteria, and HHT is suspected if they have two of the criteria:
- Nosebleeds that are spontaneous and recurrent
- Telangiectases are prevalent at characteristic sites, such as lips, oral cavity, fingers, and nose
- AVMs are present in lung, brain, GI, liver, or spine
- Family history indicates that a parent, sibling, or child has HHT
How HHT is treated
Interventional radiologists are among the few specialists who can permanently treat hereditary hemorrhagic telangiectasia, a condition that affects approximately half a million people worldwide. As vascular experts, our team performs minimally invasive procedures for PAVMs and telangiectasia, blocking blood flow to the affected area to prevent symptoms and complications.
Along with procedures that target specific blood vessels, there are medications that can help manage HHT symptoms more broadly. These include pills that slow the breakdown of blood clots to reduce bleeding, as well as intravenous therapies that help prevent the formation of poorly formed blood vessels. Clinical trials are also underway to explore additional options for reducing bleeding and blood vessel problems.
Expert care for HHT
Penn Medicine's Hereditary Hemorrhagic Telangiectasia (HHT) Program brings together specialists in hematology, genetics, interventional radiology, and other areas to diagnose, monitor, and treat this complex condition.
We also offer long-term follow-up, second opinions, counseling, and evaluations for family members who may be at risk. Through clinical research and participation in HHT studies, we continue working to improve treatment options for people living with this rare condition.