HHT is more than nosebleeds. It’s a whole-body, whole-system disease.
Hereditary hemorrhagic telangiectasia affects blood vessels throughout the body, and some of its most serious complications can exist without obvious symptoms. Learning how HHT can affect you—and what can be screened for, monitored, and treated—is an important part of living well with the disease.
What HHT is
A difference in how blood vessels form
Hereditary hemorrhagic telangiectasia (HHT) is a genetic condition that changes how blood vessels form. In most of the body, arteries carry blood at high pressure into a network of tiny capillaries, which slow that flow before it reaches the veins. In HHT, some of those capillary networks do not develop. An artery connects straight to a vein, and the vessel that results is fragile enough to bleed.
That is why HHT causes bleeding rather than clotting problems. It is a blood vessel condition, not a clotting disorder—a distinction worth carrying into any appointment with a clinician who has not treated HHT before.
HHT is also known as Osler-Weber-Rendu syndrome, named for the physicians who first described it in the late 1800s.
HHT by the numbers
1 in 4,000
People are affected by HHT
80%
Of people with HHT are undiagnosed
27 yrs
Average delay before an HHT diagnosis
95%
Develop symptoms over their lifetime
Signs and symptoms
Where HHT shows up, and what it does there
Two types of vascular abnormality characterize HHT. Telangiectasia are small vascular malformations that appear as 1-2 mm red spots on the surface of the skin, the lining of the nose, and the lining of the intestinal tract. Arteriovenous malformations (AVMs) are large vascular malformations that can occur in the liver, lungs, brain, and sometimes the spine, and they cannot be seen without proper imaging procedures.
Open a location on the figure below to see what is known about it. Each one is numbered to match a marker.
1 · Brain
At least 10% of HHT patients have brain VMs which can be successfully treated in most cases. The HHT International Guidelines recommend brain VM screening for anyone diagnosed with HHT, regardless of their age, because they can rupture without warning.
VMs can form at least into young adulthood, so repeated screening is necessary. The chance of rupture is 0.3-0.5% per year. Children are more likely to present with hemorrhage than adults.
Seizures and headaches can also result from VMs in the brain.
2 · Nose
Most people with HHT have telangiectasia on the skin inside their nose, which cause nosebleeds (epistaxis) when ruptured.
- HHT is hereditary, so nosebleeds often run in families that are affected by this disease.
- Recurring nosebleeds affect about 90% of people with HHT and are the most common symptom of the disease.
- Nosebleeds are often the earliest symptom of HHT; typically nosebleeds begin around age 12, but can appear as early as infancy or as late as adulthood.
- The absence of nosebleeds does not mean a patient does not have HHT. It has recently been reported that some patients will experience their first nosebleed at age 70.
- Nosebleeds can vary from a mere social nuisance to severe, sometimes causing lots of blood loss and even transfusion dependence. The Epistaxis Severity Score (ESS) is a standardized tool for measuring how severe your nosebleeds are. Sharing your ESS score with your physician is important for determining a proper treatment plan.
- Iron deficiency and anemia are common among people with HHT and are primarily a consequence of nasal and GI bleeding. This can lead to shortness of breath, exercise intolerance, and fatigue. Iron deficiency tends to be both under-diagnosed and under-treated even though anemia is found in approximately 50% of all HHT patients.
3 · Lungs
At least 40% of people with HHT have lung AVMs (also known as pulmonary AVMs, or PAVMs). A recent study indicated that 60% of children with HHT will develop PAVMs and 30% who had a negative PAVM screening will develop one within 5 years. People with HHT1 (ENG) are 5-10 times more likely to have PAVMs.
Lung AVMs can lead to serious complications, such as stroke, so it is important to be screened.
- If the artery leading into a lung AVM is larger than 2-3 mm in diameter, small blood clots can travel through the lung AVM and go to the brain causing a stroke.
- Migraine headaches can be a sign of brain abscess caused by lung AVMs but most PAVMs are easily treatable.
- Lung AVMs can cause low oxygen saturation which, along with pulmonary hypertension, can lead to shortness of breath, exercise intolerance, and fatigue.
- PAVMs have a high risk of rupturing when pregnant due to increased blood volume.
Most PAVMs are easily treatable once identified through screening.
4 · Liver
Liver vascular malformations (VMs) are present in 75% of people with HHT, but range in severity with approximately 10% causing symptoms and complications. Liver VMs occur more commonly in women and often present after the age of 50.
Symptoms are typically more severe in patients with HHT2 (ACVRL1). Symptoms may occur with aging, when the heart has been overworked for years by pumping extra blood through the low-resistance pathway of the AVM and by chronic anemia. This can lead to shortness of breath, exercise intolerance, and fatigue. Other complications can include high output heart failure, portal hypertension, encephalopathy, mesenteric ischemia, and biliary ischemia.
Treatments may include use of anti-angiogenic drugs or liver transplant.
5 · Stomach and intestines
- 80% of HHT patients have telangiectasia in the stomach or intestines, though it is estimated that only 30% will develop obvious gastrointestinal (GI) bleeding which usually starts when the patient is 50 or 60.
- HHT-related GI bleeding risk increases with age.
- Telangiectasia in the GI tract do not cause pain.
- Symptoms of GI bleeding include black or bloody stool and/or anemia.
Definitions of GI bleeding in HHT patients:
- Mild HHT-related GI bleeding: Patient who meets their hemoglobin goals with oral iron replacement.
- Moderate HHT-related GI bleeding: Patient who meets their hemoglobin goals with IV iron treatment.
- Severe HHT-related GI bleeding: Patient who does not meet their hemoglobin goals despite adequate iron replacement, or requires blood transfusions.
Hemoglobin goals should reflect age, gender, symptoms and co-morbidities (Faughnan et al., 2020).
6 · Spine
Spinal AVMs are rare, affecting only about 1% of HHT patients. They can cause back pain or swelling, upper leg pain, and sometimes lead to loss of feeling or mobility in an arm or leg. If untreated, spinal AVMs can lead to further motor or sensory deficit, aneurysm, and high blood pressure.
7 · Hands, face, and mouth
- 90-95% of people with HHT have telangiectasia on the skin of the hands, face, and mouth, although they may not be visible until age 30 or 40.
- Telangiectasia appear as tiny red or purple spots between the size of a pinpoint and pinhead.
- Rupture and bleeding of telangiectasia on the mouth, face, or hands is less common than of those in the nose.
- Telangiectasia have a tendency to become more numerous with increased age.
Two of these seven are visible from the outside: the nose and the skin. The rest need imaging to find, which is what screening is for. These symptoms can occur in people without HHT, but a family history of them could indicate HHT.
Genetics and inheritance
HHT runs in families, and that is useful information
HHT is inherited in an autosomal dominant pattern. A person with HHT carries one changed copy of the gene and one unchanged copy, and each child has a 50% chance of inheriting the changed copy. HHT does not skip generations, and it affects people of every sex, race, and ethnic background.
Nearly everyone with HHT inherited it from a parent who also has HHT. In very rare cases, a change in an HHT gene occurs for the first time in the egg or sperm cell of someone who does not have HHT themselves. In those cases the child has HHT even though neither parent does.
Once a family’s genetic change is known, relatives can be tested for that specific change. A negative result can spare someone a lifetime of screening. A positive result means screening can begin before anything goes wrong.
What the genetics mean
50%
Chance each child of an affected parent inherits HHT
90%
Of cases involve the ENG or ACVRL1 gene
10–15%
Have no change found in a known HHT gene
The genes associated with HHT
Four genes are currently associated with HHT, and they are not equally common. Which one a family carries changes what their care team watches for.
| Gene | How often | What it means |
|---|---|---|
| ENG HHT type 1 | About 90% of cases involve ENG or ACVRL1 | People with HHT1 are 5 to 10 times more likely to have pulmonary AVMs. |
| ACVRL1 HHT type 2 | About 90% of cases involve ENG or ACVRL1 | Liver involvement is typically more symptomatic in HHT2. |
| SMAD4 | 3% to 5% of people with a clinical diagnosis | Causes a combined syndrome of HHT and juvenile polyposis, so regular colonoscopy starting in the teenage years is part of care. |
| BMP9/GDF2 | Fewer than 1% worldwide | Reported in only a handful of people, so it is not typically part of routine genetic testing for HHT. |
| No change found | About 10% to 15% | The diagnosis is made on clinical evaluation alone. |
Because 10% to 15% of people diagnosed with HHT do not have a change in one of the identified HHT genes, a negative genetic test does not mean a person does not have HHT. There are likely other genes that cause the symptoms of HHT that have not yet been identified.
How inheritance works
One parent with HHT, a 50% chance with every pregnancy
Every pregnancy carries the same 50% chance, independently of the others. Four children does not mean two will be affected, and a family can have all four affected or none at all.
Across life stages
HHT in children and in pregnancy
HHT does not wait for adulthood, and it does not pause for pregnancy. Both stages have their own screening and care recommendations.
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HHT in children
A child of a parent with HHT can be evaluated before any symptom appears. Nosebleeds often start in childhood, and lung and brain malformations can be present from birth, so pediatric screening follows its own set of guideline recommendations.
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Pregnancy and HHT
Most pregnancies in people with HHT go well. Pulmonary and brain malformations do carry added risk during pregnancy and delivery, which is why screening beforehand, and care at a center familiar with HHT, changes how that risk is handled.
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Testing your family
Because each child of an affected parent has a 50% chance of inheriting HHT, a diagnosis in one person is information for a whole family. Genetic counseling helps decide who to test and when.