What's hereditary hemorrhagic telangiectasia?
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is an autosomal dominant vascular disorder of dysregulated angiogenesis, caused in over 90% of cases by pathogenic variants in ENG or ACVRL1 (with SMAD4 and GDF2 accounting for smaller shares), all in the TGF-β/BMP9 pathway. It is defined clinically by the Curaçao criteria: recurrent spontaneous epistaxis, mucocutaneous telangiectasias, visceral arteriovenous malformations (pulmonary, hepatic, cerebral), and a first-degree relative with the condition. Gastrointestinal bleeding and iron-deficiency anaemia are common. There is no curative drug therapy; management is largely supportive, including iron replacement and transfusion, antifibrinolytics, embolization or ablation of AVMs, and emerging anti-angiogenic therapy such as bevacizumab.
| Also indexed as | ORPHA:774, MONDO:0019180 |
|---|---|
| Features mapped | 21 |
| Treatments mapped | 9 |
| Published sources | 24 |
| Last reviewed | 2026-08-04 |
Signs and symptoms
Mucosal telangiectasiae
Telangiectasias are small clusters of widened vessels that appear as red spots, often on the lips, tongue, and lining of the mouth. They are fragile and bleed easily.
Telangiectasia of the skin
Skin telangiectasias in hereditary hemorrhagic telangiectasia are small clusters of fragile blood vessels that can look like dots, lines, or splinters. They are commonly seen on the upper body, the lining of the mouth, and the nail beds.
Gastrointestinal arteriovenous malformation
Hereditary hemorrhagic telangiectasia can produce abnormal blood vessels and telangiectasias throughout the lining of the digestive tract. These can bleed slowly over time, leading to chronic blood loss, iron-deficiency anemia, and at times a need for repeated transfusions.
Transient ischemic attack
A transient ischemic attack is a brief stroke-like episode. In hereditary hemorrhagic telangiectasia it can occur as a complication of pulmonary arteriovenous malformations, the abnormal vessel connections in the lungs.
Pulmonary arterial hypertension
Pulmonary arterial hypertension is high blood pressure in the arteries of the lungs. It is one of the lung-related complications that can occur in hereditary hemorrhagic telangiectasia.
Telangiectasia
Telangiectasias are small clusters of widened, fragile blood vessels near the surface. In hereditary hemorrhagic telangiectasia they typically appear in the nasal cavity, lips, tongue, fingertips, and the lining of the digestive tract.
Cerebral arteriovenous malformation
Malformed vessels can occur in the brain as well. These are screened for because, although uncommon, they carry a risk of bleeding.
Pulmonary embolism
A pulmonary embolism is a blood clot that blocks an artery in the lungs. It has been reported in a person with hereditary hemorrhagic telangiectasia.
Congestive heart failure
Large arteriovenous malformations, especially in the liver, can force the heart to pump much more blood than normal. Over time this can lead to high-output heart failure.
Pulmonary arteriovenous malformation
Pulmonary arteriovenous malformations are abnormal direct connections between arteries and veins in the lungs. They are important because they can let clots or bacteria bypass the lungs and reach the brain, causing stroke or infection, so screening for them is standard.
Hepatic arteriovenous malformation
Arteriovenous malformations can also form in the liver. They are often silent but in some people lead to heart strain or liver problems.
Hemoptysis
Hemoptysis means coughing up blood. In hereditary hemorrhagic telangiectasia it can occur as one of the serious complications of pulmonary arteriovenous malformations, the abnormal vessel connections in the lungs.
Tongue telangiectasia
Telangiectasias on the tongue are clusters of small widened blood vessels there. In one cohort of people with hereditary hemorrhagic telangiectasia, the tongue was among the most commonly affected sites, involved in about 76 percent of patients.
Lip telangiectasia
Telangiectasias on the lips are clusters of small widened blood vessels there. In one cohort of people with hereditary hemorrhagic telangiectasia, the lips were among the most commonly affected skin sites, involved in about 79 percent of patients.
Nasal mucosa telangiectasia
Telangiectasias in the lining of the nose are clusters of fragile blood vessels there. When they rupture they cause the recurring nosebleeds that are the most common feature of hereditary hemorrhagic telangiectasia.
Anemia
Repeated bleeding from the nose and gut commonly leads to iron-deficiency anemia, which leads to fatigue and may need iron treatment or transfusions.
Cerebral hemorrhage
Bleeding in the brain, or hemorrhagic stroke, is one of the neurologic risks in hereditary hemorrhagic telangiectasia. It can happen because of arteriovenous malformations, abnormal vessel connections in the brain.
Epistaxis
Nosebleeds are the most common feature of hereditary hemorrhagic telangiectasia. They happen when small fragile blood vessels in the nasal lining (telangiectasias) rupture, usually start in childhood, and affect about 90 to 95 percent of people with the condition.
Gastrointestinal hemorrhage
Telangiectasias in the stomach and intestines can bleed, often slowly and invisibly, which is a major cause of the iron-deficiency anemia seen in the condition.
Venous thrombosis
Venous thromboembolism is a blood clot forming in a vein. It is among the complications that can occur in hereditary hemorrhagic telangiectasia, alongside bleeding and other problems.
Spontaneous, recurrent epistaxis
Recurrent spontaneous nosebleeds are the most common and usually the first symptom, affecting the great majority of people and often starting in childhood. They come from fragile telangiectasias in the lining of the nose.
How it is diagnosed
Hereditary hemorrhagic telangiectasia
Diagnosed using: Curacao criteria (clinical diagnosis).
“…based on the Curaçao criteria: epistaxis, telangiectases, arteriovenous malformations in internal organs, and family…”
Hereditary hemorrhagic telangiectasia
Diagnosed using: Genetic testing for ENG, ACVRL1, and SMAD4.
“Genetic mutations that have been identified include ENG, ACVRL1/ALK1, and MADH4/SMAD4, among others.”
Hereditary hemorrhagic telangiectasia
Diagnosed using: transthoracic contrast echocardiography (bubble echo) screening for pulmonary AVMs.
“Agitated saline contrast echocardiography ('bubble echo') is the recommended method for detecting and grading RLS, as outlined in International HHT Guidelines.”
Hereditary hemorrhagic telangiectasia
Diagnosed using: chest CT / CT angiography for pulmonary AVMs.
“Diagnostic assessment relies on echocardiographic contrast studies and CT angiography.”
Hereditary hemorrhagic telangiectasia
Diagnosed using: genetic testing combined with Curacao criteria.
“…it is recommended that genetic tests are used in combination with the clinical Curaçao criteria to confirm the…”
Treatment and management
What the research describes, not a recommendation. Treatment decisions belong with your clinician.
This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.
bevacizumab
Bevacizumab is an anti-angiogenic medicine (it blocks abnormal vessel growth). Given into a vein it has emerged as a promising treatment for reducing severe bleeding, though it manages rather than eliminates the disease.
Used to help with: Hereditary hemorrhagic telangiectasia.
“Anti-angiogenic agents such as bevacizumab have emerged as a promising systemic therapy in reducing bleeding complications but are not curative.”
tranexamic acid
Tranexamic acid is an antifibrinolytic medicine that helps blood clots hold, and it can reduce the frequency of nosebleeds.
Used to help with: Spontaneous, recurrent epistaxis.
“Tranexamic acid significantly reduced the epistaxis frequency, MD -1.93, 95%CI [-3.58, -0.28].”
transcatheter embolization of pulmonary AVMs
Children with large or significant pulmonary arteriovenous malformations from hereditary hemorrhagic telangiectasia are treated with transcatheter embolization, a procedure that closes off the abnormal vessel from within.
Used to help with: Hereditary hemorrhagic telangiectasia.
“Embolisation represents the standard of care for significant PAVMs with periodic radiological surveillance recommended.”
intravenous bevacizumab
Bevacizumab is an antibody that blocks a growth signal called VEGF. By reducing the formation of abnormal blood vessels, it has emerged as a treatment that may modify the course of hereditary hemorrhagic telangiectasia.
Used to help with: Hereditary hemorrhagic telangiectasia.
“IV bevacizumab therapy was associated with improved iron parameters and reduced transfusion requirements in patients with HHT-related bleeding.”
iron replacement therapy
Managing hereditary hemorrhagic telangiectasia includes replacing iron lost through bleeding, given as intravenous iron, to treat the anemia caused by chronic blood loss.
Used to help with: Hereditary hemorrhagic telangiectasia.
“Management includes intravenous iron therapy or blood transfusion, antifibrinolytics (e.g tranexamic acid), ablation…”
blood transfusion
Managing hereditary hemorrhagic telangiectasia can include blood transfusion to replace blood lost through bleeding and to treat severe anemia.
Used to help with: Hereditary hemorrhagic telangiectasia.
“Management includes intravenous iron therapy or blood transfusion, antifibrinolytics (e.g tranexamic acid), ablation…”
endoscopic ablation of gastrointestinal telangiectasias
In hereditary hemorrhagic telangiectasia, bleeding telangiectasias in the digestive tract can be treated through an endoscope by ablation, a procedure that seals off the abnormal vessels.
Used to help with: Hereditary hemorrhagic telangiectasia.
“The patient required transfusion of five units of packed red blood cells and underwent endoscopic ablation of multiple telangiectasias in the stomach and duodenum.”
thalidomide
Thalidomide, an antiangiogenic drug, has been used along with blood transfusion to treat bleeding in people with hereditary hemorrhagic telangiectasia.
Used to help with: Hereditary hemorrhagic telangiectasia.
“Treatment included blood transfusion and thalidomide in 3 patients. HHT has to be considered during the evaluation of iron deficiency anemia in adult patients.”
stereotactic radiosurgery for brain AVMs
Stereotactic radiosurgery, a focused form of radiation, achieved high rates of closing off brain arteriovenous malformations with little harm in people with hereditary hemorrhagic telangiectasia.
Used to help with: Hereditary hemorrhagic telangiectasia.
“SRS for HHT-BAVMs achieved high obliteration rates with minimal morbidity.”
What changes how it shows up
Carrying the genetic change is not the whole story. The factors below are described in the research mapped here as changing whether, or how strongly, the condition appears. They modulate how the genotype is expressed; they do not, on their own, cause or cure it.
ENG
Hereditary hemorrhagic telangiectasia is caused by loss-of-function mutations in genes of the BMP9/BMP10 signaling pathway. The main genes are ENG, ACVRL1 (also called ALK1), and SMAD4, which define the major subtypes HHT1, HHT2, and the juvenile-polyposis form.
Described as modulating: Hereditary hemorrhagic telangiectasia.
“HHT is caused by heterozygous loss-of-function mutations in genes involved in the BMP9/BMP10 signaling pathway-primarily ENG, ACVRL1 (also known as ALK1), and SMAD4-which define the major HHT subtypes (HHT1, HHT2, and HHT-JP).”
ACVRL1
Most cases of hereditary hemorrhagic telangiectasia, over 90 percent, are caused by mutations in three genes that work in the TGF-beta signaling pathway: endoglin (ENG), activin receptor-like kinase 1 (ACVRL1), and SMAD4.
Described as modulating: Hereditary hemorrhagic telangiectasia.
“Pathogenic variants in three genes, endoglin (ENG), activin receptor-like kinase 1 (ACVRL1) and mothers against decapentaplegic homolog 4 (SMAD4), all part of the transforming growth factor-β signalling pathway, account for over 90% of HHT cases.”
How to read the evidence labels
Where this comes from
This guide is built from 24 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.
Take it further
Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.