What is Hereditary Hemorrhagic Telangiectasia?
Hereditary hemorrhagic telangiectasia, also known as Osler-Weber-Rendu syndrome, is a hereditary disorder that affects the vascular system (blood vessels). People with HHT develop abnormal blood vessels (arteriovenous malformations or AVMs) that lack the capillaries that are usually present between each artery and vein. In the AVMs, the arterial blood flows directly into a vein without first having to squeeze through the small capillaries. These AVMs tend to be fragile and can rupture and bleed. The smaller AVMs are called telangiectasia and occur primarily in the nose, mouth, and skin of the face and hands, as well as the lining of the stomach and intestines. The larger abnormal blood vessels (AVMs) occur in the brain, lung, liver and spine.
Telangiectases in the nose, along with the nosebleeds they cause, are the most common features of HHT. About 90% of people with HHT have recurring nosebleeds by the time they reach middle age. They range from mild to severe and can cause an individual to require regular blood transfusions. Telangiectases of the skin of the hands and face, as well as of the lining of the lips and mouth are found in 90% of all people with HHT. However, these often do not become apparent until the 30’s or 40’s.
Bleeding from the stomach and bowels (gastrointestinal or GI bleeding) will develop in 30% of people with HHT. The GI bleeding in HHT can range from mild to severe and can cause an individual to require regular blood transfusions. Telangiectases in the stomach and bowels do not cause pain or discomfort. Most HHT patients with GI bleeding don’t have symptoms but are anemic or iron deficient. Sometimes they can have black or bloody stools as well. Anemia can cause fatigue, shortness of breath, chest pain or lightheadedness.
Lung AVMs are found in approximately 40% of people with HHT and they are often multiple. AVMs in the lung are at risk of rupturing, particularly during pregnancy. This can lead to life-threatening hemorrhage. In addition, people with untreated lung AVMs, loose the capillary ability to filter for impurities (clots, bacteria, air bubbles) from the blood before the blood circulates to the brain. As such, people with lung AVMs are at risk of stroke and brain abscess, which can be debilitating and life-threatening. Lung AVMs can be effectively treated with a procedure called transcatheter embolization. People with lung AVMs may be short of breath and easily fatigued and suffer from migraine headaches, but sometimes they have no symptoms before developing stroke or hemorrhage.
Brain AVMs are present in approximately 10% of people with HHT. They can hemorrhage and cause stroke and/or death, or can lead to seizures. Brain AVMs can be treated, but expert care is required. Spinal AVMs are very rare but can also hemorrhage. These can be treated similarly to brain AVMs.
Liver AVMs are present in 75% of HHT patients, but only cause symptoms in about 7% of people with HHT. They are unlikely to rupture, and most do not require treatment. When they are large and numerous, they can cause heart and liver failure, usually later in life.
It is unlikely that a person with HHT will have all of the symptoms and AVMs described. One of the characteristics of HHT is its variability, even within a family. One cannot predict how likely someone is to have one of the hidden, internal AVMs based on how many nosebleeds or skin telangiectases one has. Additionally, some people will have mild disease while others, even within the same family, may have severe bleeding in internal organs which can be life threatening.
Who gets Hereditary Hemorrhagic Telangiectasia?
HHT occurs in children and adults, men and women and affects all ethnicities.
What causes Hereditary Hemorrhagic Telangiectasia?
HHT is caused by defects in at least three genes, but only one abnormal gene is the cause in one family. The abnormal gene found on Chromosome 9 is called endoglin and causes HHT1. The abnormal gene on Chromosome 12 is called activin-like kinase 1 (ALK1) and causes HHT 2. Endolgin and Alk1 are through to cause most of the HHT cases. The third gene, MADH4, causes symptoms in HHT and multiple colon polyps at an early age. Most people with MADH4 mutation have combined HHT and Juvenile Polyposis. It is thought that two other abnormal genes, found on Chromosome 5 and 7 can cause HHT: the genes have yet to be discovered. HHT is considered an autosomal dominant disorder, which means that each child born of an HHT affected parent will have a 50% chance of inheriting the abnormal gene.
How is Hereditary Hemorrhagic Telangiectasia diagnosed?
HHT can be diagnosed through genetic testing and/or by clinical criteria (the Curacao Criteria). These criteria include:
- Nosebleeds that are spontaneous and recurrent that can be mild or severe
- Multiple telangiectases on the skin or in the mucous membranes. The telangiectases are small red spots that blanch under pressure located on the lips, oral cavity, fingers, palm of the hands and nose.
- Arteriovenous malformations (AVMs) or telangiectases in one or more of the internal organs, including the lungs, brain, liver, intestines, stomach, and spinal cord. A first-degree relative (brother, sister, parent or child) with HHT, based on these diagnostic criteria.
A diagnosis is considered definite when three or more of the criteria are present, possible or suspected when two findings are present, and unlikely with fewer than two findings.
Learn more about diagnosis of HHT in the International HHT Guidelines.
What is the treatment for Hereditary Hemorrhagic Telangiectasia?
Treatment of a person’s HHT depends on which parts of the body are affected. Some aspects (nosebleeds) are treated symptomatically, whereas others are treated preventatively (lung and brain AVMs).
Treatments for nosebleeds can range from lubrication of the nasal mucosa, laser therapy and septal dermoplasty for severe transfusion dependent patients. Telangiectases of the skin can be treated with laser therapy.
Lung and brain AVMs should be treated before they cause complications. Lung AVMs can almost always be treated completely with embolization, a high-tech low-risk procedure. Brain AVMs are treated in different ways depending on the size, structure and location in the brain. Surgery, embolization and stereotactic radio surgery can all be used, separately or in combination to successfully treat brain AVMs.
Bleeding from the stomach or intestines is generally treated only if it causes anemia (low blood count). Iron replacement therapy is the first line of defense. If iron therapy does not control the anemia, transfusion and endoscopic treatments using a heater probe, APC or laser are options. Hormonal therapy, and other medical therapies to control bleeding, are also helpful in some people.
Liver AVMs are currently treated only if a person shows signs of liver or heart failure as a result of a liver VM. Decisions regarding treatment of liver VMs are made on a case-by-case basis and should be managed by a physician very familiar with the liver manifestations of HHT.
The recommended treatment for a telangiectasia or AVM depends on its size and location in the body.
Learn more about management of HHT in the International HHT Guidelines.