Hereditary hemorrhagic telangiectasia, often called HHT or Osler-Weber-Rendu syndrome, is a genetic blood vessel disorder that affects roughly 1 in 10,000 people worldwide. It causes abnormal connections between arteries and veins, leading to fragile spots that bleed easily on the skin and mucous membranes, and potentially dangerous malformations in the lungs, liver, and brain. Because it is inherited in an autosomal dominant pattern, a single copy of a mutated gene from either parent is enough to cause the condition, and each child of an affected person has a 50 percent chance of inheriting it.
What Goes Wrong in the Blood Vessels
In a healthy circulatory system, arteries carry oxygen-rich blood out from the heart, and veins carry it back. Between them sits a network of tiny capillaries where oxygen and nutrients pass into tissues. In HHT, certain blood vessels skip the capillary step entirely. Arteries connect directly to veins, forming what doctors call arteriovenous malformations, or AVMs. Without the buffering effect of capillaries, thin-walled veins receive blood at arterial pressure, making them prone to rupture and bleeding.
When these abnormal vessels are small and sit near the surface of the skin or mucous membranes, they appear as tiny red spots called telangiectases. When they form deeper inside an organ like the lungs or liver, they are larger AVMs that can shunt significant volumes of blood past the organ’s filtering or processing tissue. The consequences range from chronic nosebleeds to stroke, depending on where the malformations develop.
The Genes Behind HHT
More than 90 percent of HHT cases trace back to mutations in one of three genes: ENG, ACVRL1, or SMAD4. Mutations in ENG and ACVRL1 are nearly equally responsible for the majority of cases and define the two main subtypes, HHT1 and HHT2, respectively.1JCI Insight. Hereditary hemorrhagic telangiectasia: from signaling insights to therapeutic advances The proteins encoded by these genes are part of a signaling chain that tells blood vessel cells how to grow, divide, and organize themselves. When either protein is defective, the signals go haywire and blood vessels form without proper structure.
A small fraction of patients carry mutations in SMAD4, which sits further downstream in the same signaling pathway. These patients develop a distinct overlap condition called Juvenile Polyposis-HHT syndrome, which combines the vascular problems of HHT with a predisposition to polyps in the gastrointestinal tract that can become cancerous.2PubMed Central. Hereditary Hemorrhagic Telangiectasia with SMAD4 Mutations Is Associated with Fatty Degeneration of the Left Ventricle, Coronary Artery Aneurysm, and Abdominal Aortic Aneurysm This overlap means SMAD4 patients need more aggressive cancer screening than other HHT patients.3European Journal of Human Genetics. Outcomes of patients with Juvenile Polyposis-Hereditary Haemorrhagic Telangiectasia caused by pathogenic SMAD4 variants in a pan-Scotland cohort A remaining minority of clinically diagnosed patients have no identifiable mutation in any of the three genes, suggesting at least one more causative gene has yet to be found.
The genetic subtype matters beyond academic interest because HHT1 and HHT2 tend to affect different organs at different rates. Patients with HHT1 (ENG mutations) are far more likely to develop lung AVMs than those with HHT2. In screening studies, about 85 percent of HHT1 patients showed evidence of blood bypassing the lung capillaries on echocardiography, compared with roughly 35 percent of HHT2 patients.4Chest. Screening in Hereditary Hemorrhagic Telangiectasia Patients Knowing which gene is involved helps doctors decide how aggressively to screen for complications in specific organs.
Nosebleeds and Visible Telangiectases
Recurrent nosebleeds are the hallmark symptom. They affect more than 96 percent of patients and are often the first sign of the disease, sometimes starting in childhood.5PubMed. The effects of epistaxis on health-related quality of life in patients with hereditary hemorrhagic telangiectasia Unlike ordinary nosebleeds caused by dry air or minor trauma, HHT nosebleeds come from telangiectases lining the nasal septum. They can happen daily, last minutes to hours, and lead to chronic iron-deficiency anemia over time. Some patients lose enough blood that they need regular iron infusions or blood transfusions.
The same fragile spots also appear on the lips, tongue, fingertips, and the lining of the mouth. They look like small red or purple dots, typically a few millimeters across, that blanch when you press on them and refill immediately. In many families, the telangiectases become more numerous with age, so a teenager with HHT might have few visible signs while a grandparent with the same mutation has dozens.
When the Lungs Are Involved
Nearly half of people with HHT develop pulmonary arteriovenous malformations, abnormal connections in the lungs that let blood skip past the air sacs where it would normally pick up oxygen.6PubMed Central. Hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations: clinical aspects This has two consequences. First, oxygen levels in the blood drop, because some blood never gets exposed to fresh air. In one large patient series, shortness of breath with exertion affected more than half of patients with lung AVMs, and about 43 percent were measurably low on oxygen even at rest.7Medicine. Pulmonary Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia
Second, and more insidiously, the lung’s capillary bed normally acts as a filter that traps tiny blood clots and bacteria before they can reach the brain. When blood bypasses that filter through an AVM, clots and bacteria can travel straight to the brain, causing stroke or brain abscess. These complications can strike people who feel perfectly well and have no idea they have a lung AVM. This is why screening is considered so important: catching and treating a lung AVM before it causes a stroke is far better than treating the stroke afterward.
Screening for lung and brain vascular malformations is standard practice at North American HHT centers of excellence, though the specifics of brain screening still vary between centers.8PubMed Central. Screening for pulmonary and brain vascular malformations is the North American standard of care for patients with hereditary hemorrhagic telangiectasia (HHT): A survey of HHT Centers of Excellence In children with a confirmed HHT gene mutation, guidelines recommend initial screening and then repeated checks at least every five years, because new lung AVMs can develop throughout life.9Current Opinion in Pediatrics. Hereditary hemorrhagic telangiectasia – pediatric review
Liver and Gastrointestinal Complications
AVMs in the liver are common in HHT, though many remain silent for years. When liver AVMs are large enough to shunt significant blood volume, the heart has to pump harder to compensate. A study examining predictors of heart failure symptoms in these patients found that both a widened hepatic artery and low hemoglobin were independent predictors of developing heart failure, underscoring the interplay between chronic bleeding and cardiac strain.10PubMed Central. Predictors of heart failure symptoms in hereditary hemorrhagic telangiectasia patients with hepatic arteriovenous malformations
Gastrointestinal bleeding is the other major source of blood loss beyond nosebleeds. Telangiectases develop throughout the stomach and small intestine, and they bleed slowly and chronically. Patients with GI involvement tend to have significantly lower hemoglobin and ferritin levels, and about two-thirds end up needing red blood cell transfusions or having hemoglobin drop below 8 g/dL during follow-up.11PubMed Central. Gastrointestinal Bleeding in Patients with Hereditary Hemorrhagic Telangiectasia: Risk Factors and Endoscopic Findings Unlike nosebleeds, GI bleeding is often invisible to the patient until anemia becomes severe, making regular blood counts an essential part of HHT management.
How HHT Is Diagnosed
Doctors use a set of four clinical criteria known as the Curaçao criteria to identify HHT. The criteria are: spontaneous and recurrent nosebleeds; visible telangiectases in characteristic locations (lips, mouth, fingers, nose); visceral AVMs (in the lungs, liver, brain, or GI tract); and a first-degree relative who also has HHT. Meeting three or four of the criteria makes the diagnosis “definite,” two makes it “possible,” and fewer than two makes HHT “unlikely.”
These clinical criteria perform well. In patients who meet the “definite” threshold, genetic testing finds a causative mutation in ENG, ACVRL1, or SMAD4 in about 97 percent of cases.12Genetics in Medicine. Curaçao diagnostic criteria for hereditary hemorrhagic telangiectasia is highly predictive of a pathogenic variant in ENG or ACVRL1 (HHT1 and HHT2) The clinical diagnosis also shows strong predictive value: a definite clinical diagnosis had a 100 percent positive predictive value in one validation study, and an “unlikely” result had a negative predictive value of about 98 percent.13PubMed. Hereditary hemorrhagic telangiectasia: how accurate are the clinical criteria?
Genetic testing becomes especially helpful in two situations. The first is when the clinical picture is ambiguous, the “possible” category. About a third of patients in the “possible” group turn out to carry a causative mutation.14PubMed. Hereditary hemorrhagic telangiectasia: how accurate are the clinical criteria? The second is in children and young adults from known HHT families. Because symptoms like telangiectases accumulate with age, a young person might not yet meet enough clinical criteria for a definite diagnosis, yet they could already be developing silent lung or brain AVMs that need treatment. A genetic test can settle the question years before the clinical picture becomes clear, allowing screening and preventive care to begin early.
Treating Nosebleeds
Managing nosebleeds in HHT starts with the simple and escalates as severity demands. Humidification, saline sprays, and topical moisturizers help protect the fragile nasal lining. Laser cauterization can seal individual telangiectases, though new ones tend to form over time, requiring repeat sessions.
Tranexamic acid, a drug that helps blood clots stay intact, has shown benefit in controlled trials. One European crossover trial found that tranexamic acid reduced the total duration of nosebleeds per month by about 17 percent compared with placebo.15PubMed. Tranexamic acid for epistaxis in hereditary hemorrhagic telangiectasia patients: a European cross-over controlled trial in a rare disease A separate trial reported that patients experienced a 54 percent reduction in their nosebleed severity score during the treatment period.16PubMed. Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid – a double-blind placebo-controlled cross-over phase IIIB study The discrepancy between these two figures reflects different measurement approaches, but both point in the same direction: tranexamic acid helps, though it does not eliminate the problem.
For patients with severe, refractory nosebleeds, bevacizumab, a drug originally developed for cancer that blocks the growth of new blood vessels, has emerged as a promising systemic option. A review of published cases and a center’s own experience found intravenous bevacizumab to be very promising for patients with severe nosebleeds or GI bleeding who had not responded to other treatments.17PubMed. Does severe bleeding in HHT patients respond to intravenous bevacizumab? Review of the literature and case series
When medications and laser treatments are not enough, surgical options include septodermoplasty, a procedure in which the bleeding nasal lining is removed and replaced with a skin graft. This approach can reduce the need for repeat laser treatments by over half, though it does not always stop bleeding entirely because telangiectases can grow through the graft over time.18PubMed Central. Epistaxis in hereditary hemorrhagic telangiectasia: an evidence based review of surgical management In the most extreme cases, Young’s procedure surgically closes the nasal cavity entirely, stopping airflow through the nose. By eliminating the drying effect of nasal breathing, it stops the bleeding in most patients, though they must then breathe exclusively through the mouth.19Journal of Oral Medicine and Oral Surgery. Hereditary hemorrhagic telangiectasia, embolization, and Young’s procedure: oral surgical management
Treating Lung AVMs
Lung AVMs large enough to pose a risk of stroke or significant oxygen loss are treated with embolization, a minimally invasive procedure performed through a catheter threaded into the blood vessels. An interventional radiologist guides tiny coils or plugs into the feeding artery of the AVM to block blood flow, essentially shutting it down without surgery. The procedure is done as an outpatient with minimal complications and no reported mortality in large series.20PubMed Central. Pulmonary arteriovenous malformations: endovascular therapy
The results are encouraging but not permanent. About 80 percent of patients report improved breathing afterward.21PubMed. Diffuse pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: long-term results of embolization according to the extent of lung involvement However, treated AVMs can reopen over time, and new ones can develop. Follow-up imaging is necessary, and some patients need repeat procedures. In children and adolescents, recanalization rates tend to be higher; one pediatric case series found that about 23 percent of treated lung AVMs showed persistent blood flow, with reopening of previously blocked vessels accounting for most recurrences.22PubMed. Embolotherapy for Pulmonary Arteriovenous Malformations in the Pediatric Population with Hereditary Hemorrhagic Telangiectasias-A Retrospective Case Series Younger patients were more likely to have persistent AVMs, reinforcing the need for ongoing surveillance in pediatric HHT.
HHT and Pregnancy
Pregnancy deserves special attention for women with HHT, particularly those with lung AVMs. The increased blood volume and cardiac output of pregnancy put additional pressure on already abnormal vessels. In a study of HHT-related complications during pregnancy, nearly all serious maternal events occurred in women who had lung AVMs. These complications included worsening of the shunts, fatal lung hemorrhage, and strokes.23QJM: An International Journal of Medicine. Medical complications of pregnancy in hereditary haemorrhagic telangiectasia For this reason, women with HHT are generally advised to undergo screening for lung AVMs before becoming pregnant, and any treatable AVMs should be embolized beforehand when possible.
Living with HHT
The daily burden of HHT extends well beyond the medical complications. In a large cross-sectional study, about a quarter of patients reported substantial effects on their physical functioning and their ability to carry out daily roles, while roughly one in five reported significant emotional effects.24PubMed Central. Quantifying the burden of hereditary hemorrhagic telangiectasia on quality of life and psychological health: a cross-sectional study The unpredictability is a major part of the strain. You might go days without a nosebleed and then have one erupt during a meeting, a meal, or a flight. People with HHT describe struggling to identify triggers, which makes prevention frustrating.
Qualitative research has found that the visible symptoms, blood-stained tissues, lip telangiectases, stained clothing, carry a social stigma that patients find psychologically heavy. Many people with HHT minimize the condition when talking about themselves, framing it as minor or positioning themselves as “lucky” compared with people who have more recognized illnesses. At the same time, the rarity of HHT means that many doctors outside specialist centers have limited experience with it, forcing patients into a role of self-advocacy, explaining their own disease to the clinicians treating them.25PubMed. Living with Hereditary Haemorrhagic Telangiectasia: stigma, coping with unpredictable symptoms, and self-advocacy HHT centers of excellence, which exist in many countries, can coordinate the multidisciplinary care these patients need, but not everyone lives within reach of one.
Treatments in Development
Until recently, every drug used for HHT was borrowed from another field. Tranexamic acid comes from clotting medicine. Bevacizumab was designed for oncology. That picture is beginning to shift. Several therapies specifically designed for HHT are now in preclinical development or early human trials, with some approaching the pivotal trial stage that could lead to formal approval.26PubMed Central. What’s new in hereditary hemorrhagic telangiectasia? Pazopanib, a drug that inhibits multiple signaling pathways involved in blood vessel growth, has already shown promise for patients with severe bleeding and transfusion-dependent anemia.27PubMed Central. Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia
The deeper understanding of the BMP9/BMP10-ALK1-SMAD signaling pathway that breaks down in HHT has given researchers more precise targets.28JCI Insight. Hereditary hemorrhagic telangiectasia: from signaling insights to therapeutic advances Rather than broadly blocking blood vessel growth the way bevacizumab does, newer approaches aim to correct the specific signaling deficiency in endothelial cells. Whether these targeted strategies will translate into treatments that work better or have fewer side effects than repurposed drugs remains an open question, but the pipeline is more active now than at any point in HHT research history. For patients who have spent years managing a disease with only borrowed tools, that shift carries real weight.