Information for Patients and Families
Hereditary Hemorrhagic Telangiectasia (HHT)
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 that 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 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 3 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 telangiectasias on the skin or in the mucous membranes. The telangiectasias are small red spots that blanch under pressure located on the lips, oral cavity, fingers and nose.
- Organ arteriovenous malformations (AVMs), consisting of direct connections between arteries and veins. They can be found in the lungs, brain, liver, spinal cord or gastrointestinal tract
- A first-degree relative (brother, sister, parent or child) with HHT, based on these diagnostic criteria.
A diagnosis is considered definite when 3 or more of the criteria are present, possible or suspected when 2 findings are present, and unlikely with fewer than 2 findings.
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 as 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 AVM. Decisions regarding treatment of liver AVMs 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.
Is there a blood test or DNA test available to diagnose HHT
Yes, but it is expensive, more complex than most genetic testing and generally helpful after HHT has first been confirmed in a family based on symptoms. In order to decide whether genetic testing will be helpful in your family, and if so who should be tested and in what order, it is usually necessary to be seen either at an HHT Center or a genetics clinic/department in your area.
If I have HHT, what is the chance a child of mine will have HHT?
The genetics of HHT works as follows: We each inherit two copies of each gene, one from our mother and one from our father. People with HHT have one functioning copy of the gene for HHT and one copy that is altered so that it does not function normally. Each time someone with HHT makes an egg or sperm, only one of these two genes will be included. It is completely random when each egg or sperm is formed as to whether the "altered"/HHT causing gene or the perfectly normal gene gets included. So, there is a 50% chance of passing on the altered copy with every pregnancy, but also a 50% chance to pass on only the normal gene.
Can HHT skip generations?
No, but sometimes it can look like it did. At the genetic level, you either have HHT or you don’t. There is no such thing as being a carrier of HHT (that term is reserved for genetic disorders that are recessive, not dominant like HHT). If a grandparent and grandchild both have HHT, it can safely be assumed that the "parent" in between the two also has HHT. However, remember that HHT can be EXTREMELY variable in its severity even within the same family. For example, some people with HHT get multiple nosebleeds per day and some only a couple per year. So occasionally is might look like HHT skipped a generation because the "parent" had such mild manifestations of HHT that they were not obvious.
What is the life expectancy of persons with HHT?
As long as the lung and brain malformations are treated, on average, the life expectancy of people with HHT is not significantly altered.
I’ve been told I have an AVM in an internal organ? What should I do?
In the last decade much new information has been learned and published in medical journals about the treatment of AVMs in internal organs of individuals with HHT. Unfortunately, the majority of physicians aren’t yet familiar with the most current treatment options and recommendations. If you have been told you have a "spot", a nodule or AVM from an x-ray, CT scan or MRI, you and/or your local physician should immediately contact one of the HHT Treatment Centers. The medical professionals at the HHT Treatment Centers are glad to talk to patients and physicians from around the world about when and how an AVM should be treated.
Can AVMs grow?
Many do not, but they can. Our best information about this is from observation of lung AVMs. They have been known to increase in size over time. The growth is usually quite slow, but can occasionally be more rapid such as during puberty or pregnancy, or when combined with certain heart valve problems.
My nosebleeds are mild. Does this mean that even if I do have HHT, I have a “mild” case?
Not necessarily. About 30-50% of people with HHT will have at least one AVM in the lungs and about 5-20% will have an AVM in the brain. There doesn't seem to be a correlation between the severity of the nosebleeds and what's "inside" the body. Since there is no way to predict who will have an AVM of the lung or brain, routine screening for everyone with HHT –regardless of the severity of nosebleeds- is the only way to detect their presence.
My father and I would both like to be screened for AVMs of the lung etc. How do we go about it?
We recommend that you call, or have your physician call, the nearest HHT multi-disciplinary treatment center, for recommendations about the most appropriate screening tests for your situation. Depending upon your insurance, history and preference, you can work with your family physician to get the screening done locally. Alternatively, the screening tests can be done at one of the HHT Clinics/Centers.
How can I get to one of these HHT Treatment Centers?
It’s often easier than you think. Each of these Centers has someone who helps with referrals, insurance authorization, logistics and scheduling. Since HHT is a rare disorder, there will never be expertise in all cities and medical centers. Most of the patients seen at the Treatment Centers have made arrangements to travel from out of state because they believe it is a valuable use of time and money. Often it is not necessary to have more than one visit to an HHT Center. The evaluation and screening can usually be done in one day. After the Center has seen you for evaluation and/or treatment, they are able to advise your local doctor about your long-term care needs. There is simply no substitute for being evaluated at least once in your life by physicians who specialize in your disorder.
My mother has been diagnosed with HHT and also has heart failure. Could this be related to HHT?
Some people with HHT have abnormalities in the liver that can actually either cause or contribute to heart failure. The possibility of liver AVMs should be considered in a patient with HHT and high output heart failure, particularly if the heart failure occurs at a relatively young age. Currently, most of the treatments that have been successful in treating the telangiectasia and AVMs elsewhere in the body have proven dangerous when done on the liver. It is particularly important for someone with HHT not to have any treatments involving their liver without contacting an HHT Treatment Center first.
What ethnic groups are affected by HHT?
HHT is an "equal opportunity" disorder. It is not limited to, or found predominantly in, people of a particular ethnic background, as are some other genetic disorders. HHT has been found on every continent. The HHT Foundation has had requests for information from China, Greece, India, Japan, Peru, Russia, Norway, South Africa, to name just a few. Treatment centers have been formed in many countries.
Can a person with HHT donate blood?
Yes, as long as their hemoglobin or hematocrit is at an acceptable level.
I have HHT and two small children. When should they be tested for lung AVMs (PAVMs)?
There are currently no standard guidelines for the screening and treatment of lung AVMs in children. Based on the fact that some children have had complications from lung AVMs, we do advocate screening for all children of a parent with HHT. This screening should start as a baby with pulse oximetry every two or three years. Though oximetry will not detect mildly or moderately decreased oxygen levels, it will detect severely decreased oxygen levels. It seems to be the children who have severely decreased oxygen levels who are at risk for complications. Also, if a child is complaining of shortness of breath when exercising, or is having a hard time keeping up in sports, they should additional testing for lung AVMs depending on the age. At the age of 12, all children with HHT should have the same screening for lung AVMs recommended for adults. Children can be safely treated with embolization.
What are the symptoms or signs of HHT in the gastrointestinal tract (stomach and intestines)?
Unexplained anemia or low blood count, traces of blood in the stool, (although people with nosebleeds may also have blood in the stool), black (like tar) stool in the absence of iron therapy, and in extreme cases, eliminating or vomiting blood. But they rarely cause pain.
Can my child play sports?
Yes. There are very few instances in which someone with HHT needs to limit their activity. Scuba diving is probably the one sport that individuals with HHT should avoid. Small lung AVMs may be present and cause "the bends".
Is pregnancy safe for someone with HHT?
Yes, as long as the pregnant woman has no untreated lung AVMs. We strongly recommend that all women known or suspected to have HHT be screened for lung and brain AVM prior to becoming pregnant, or during the early second trimester of pregnancy if a pregnancy is already in process. Serious complications- such as life threatening bleeding and strokes - have occurred in pregnant women with HHT who had undetected and thus untreated lung AVMs. Otherwise, serious HHT-related complications for the mother or baby are rare. Some women report that new skin telangiectases developed during their pregnancy and that their nosebleeds worsen. However, some women actually report an improvement in nosebleeds while pregnant.
It's been a while since my lung AVM was treated. Is there anything my doctor and I should be concerned about?
Follow-up evaluation at an HHT Treatment Center at regular intervals is recommended. Small AVMs in the lung, which were too small to embolize originally, may reach a size where they need to be blocked off (embolized).
What are telangiectases?
In the circulatory system, arteries take blood from the heart and distribute it to the tissues of the body via capillaries. Then the "used" blood is taken back to the heart via the veins. In HHT, some blood vessels are missing the capillaries, or the capillaries are a dilated and tangled jumble. This results in an artery and vein having a direct connection, which is not normal. These blood vessels that have missing or abnormal capillaries (telangiectases) can be fragile and rupture more easily than a normal blood vessel. Fortunately, most of the blood vessels in someone with HHT are perfectly normal.
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