Hereditary haemorrhagic telangiectasia is a genetic disorder that affects blood vessels throughout the body, causing them to form abnormally and sometimes bleed unexpectedly. While the condition varies greatly from person to person, it can lead to frequent nosebleeds, visible red spots on the skin, and in some cases, serious complications affecting internal organs.

Understanding the Global Picture

Hereditary haemorrhagic telangiectasia, often shortened to HHT or known as Osler-Weber-Rendu syndrome, affects approximately one in every 5,000 to 8,000 people worldwide^[1][2]. This makes it about as common as cystic fibrosis, though far less recognised by the general public and even many healthcare professionals^[21]. The condition appears across all racial and ethnic groups, with no particular preference for any specific population^[4].

Despite being relatively common for a rare disease, HHT remains significantly underdiagnosed. Studies suggest that as many as 90% of cases go unrecognised^[21]. Many people live with symptoms for years or even decades before receiving a proper diagnosis, and some never learn they have the condition at all^[4]. This widespread lack of awareness means that both patients and their families may miss out on important screenings and treatments that could prevent serious complications.

The distribution of HHT cases varies across different regions, with certain areas showing higher rates due to what scientists call founder effects. This occurs when a mutation becomes more common in a population descended from a small number of ancestors who carried the genetic change^[13].

What Causes This Blood Vessel Disorder

HHT is fundamentally a genetic condition, meaning it results from changes in the instructions coded within our DNA. The condition develops when there is a mutation, or alteration, in one of several genes responsible for the normal development and maintenance of blood vessels^[1]. A gene is like a blueprint that tells cells how to make specific proteins, and when that blueprint contains an error, the resulting protein may not work properly or may not be made at all.

The vast majority of HHT cases, about 90%, result from mutations in one of two specific genes: ENG or ACVRL1^[2][4]. The ENG gene provides instructions for making a protein called endoglin, while ACVRL1 guides the production of a receptor protein known as ALK1 (activin receptor-like kinase 1). Both of these proteins are found primarily in the cells that line blood vessels, called endothelial cells, where they play crucial roles in blood vessel formation and repair^[2].

When HHT type 1 occurs, it is caused by mutations in the ENG gene. HHT type 2 stems from mutations in the ACVRL1 gene. A third, less common form involves mutations in the SMAD4 gene, which creates a protein that works as part of the same signalling pathway as endoglin and ALK1^[2][13]. Scientists have identified hundreds of different possible mutations across these genes that can lead to HHT^[4].

These genetic mutations generally result in either the complete absence of the needed protein or the production of a defective version that cannot perform its normal function. When endothelial cells lack adequate amounts of functional protein, they cannot properly control the growth and structure of blood vessels^[2]. This leads to the formation of abnormal connections between arteries and veins, which are the hallmark of HHT.

Who Is at Risk and How the Condition Is Inherited

HHT is an inherited condition that passes from parents to children through families. The disorder follows what geneticists call an autosomal dominant pattern of inheritance^[1][4]. This term means two important things: first, the mutation occurs on one of the regular chromosomes (not the sex chromosomes), so both males and females are equally likely to inherit and develop the condition. Second, dominant means that having just one copy of the mutated gene is sufficient to cause HHT, even if the other copy of the gene is normal.

If you have HHT, each of your children has a 50% chance of inheriting the genetic mutation and developing the condition^[4][12]. This probability remains the same for every pregnancy, regardless of how many children you have or whether previous children were affected. The condition affects men, women, and children from all racial and ethnic backgrounds equally^[4][12].

It is important to understand that having a family history of HHT significantly increases your risk, and if one parent has the condition, their siblings may also be affected, meaning cousins could be at risk as well. However, the severity and specific symptoms can vary dramatically, even within the same family. One person might experience only mild nosebleeds, while a sibling or child could develop more serious complications affecting internal organs^[1].

Recognising the Signs and Symptoms

The symptoms of HHT can begin at almost any age, though they typically start appearing during childhood or the teenage years^[1][6]. However, some people do not develop noticeable symptoms until adulthood. The wide variation in how HHT presents itself is one reason the condition often goes undiagnosed for so long.

The single most common symptom of HHT is recurrent nosebleeds, medically termed epistaxis. These nosebleeds occur in approximately 90 to 95% of people with HHT and often begin around age 12 on average^[3][8]. The bleeding happens because abnormal blood vessels form in the lining of the nose, and these vessels are fragile and easily broken. For many patients, nosebleeds can be frequent and persistent, sometimes occurring daily. Some individuals may experience up to 18 bleeds per month^[10]. The repeated loss of blood can lead to iron deficiency anaemia, a condition where the body does not have enough healthy red blood cells to carry adequate oxygen to tissues^[1][6].

Another characteristic feature of HHT is the appearance of small red or purple spots on the skin and mucous membranes. These spots, called telangiectases, are actually tiny abnormal blood vessels visible through the skin. They typically appear later than nosebleeds, often during adolescence or adulthood^[3][6]. These spots commonly develop on the lips, tongue, fingertips, hands, face, and the lining of the mouth and nose. When you press on them, they often lighten in colour temporarily^[1][4].

Bleeding can also occur in the digestive system when telangiectases form in the stomach or intestines. This gastrointestinal bleeding affects approximately 70% of patients with HHT at some point in their lives, though it is rarely seen before age 50^[3][13]. The bleeding may be subtle and chronic, gradually leading to anaemia, or it may be more acute and noticeable.

Beyond these more visible symptoms, HHT can cause larger abnormal connections between arteries and veins in internal organs, called arteriovenous malformations or AVMs. These AVMs most commonly develop in the lungs, liver, brain, and spinal cord^[1][4]. Many people with AVMs in their organs have no symptoms at all, but these malformations can potentially cause serious complications.

Pulmonary AVMs, which occur in the lungs, affect approximately 15 to 45% of people with HHT^[3][8]. These can lead to shortness of breath, fatigue, low blood oxygen levels, or coughing up blood. More seriously, because the abnormal vessels bypass the lungs’ normal filtering function, they allow bacteria, blood clots, and air bubbles to pass through unfiltered, potentially reaching the brain and causing strokes or brain infections^[7][21].

Cerebral AVMs in the brain are present in approximately 10 to 23% of individuals with HHT^[3]. While many cause no symptoms, they can lead to severe headaches, seizures, or neurological problems. If they rupture and bleed, the consequences can be catastrophic, including stroke or death^[1].

Hepatic AVMs in the liver occur in more than 70% of patients, though only about 8% develop symptomatic liver disease^[3]. When liver involvement becomes significant, it can lead to high-output heart failure, as the heart must work much harder to pump blood through the abnormal connections. Symptoms may include fatigue, shortness of breath, and fluid retention^[4].

Steps You Can Take to Reduce Your Risk

Because HHT is a genetic condition present from birth, there is no way to prevent someone from developing the disorder if they have inherited the genetic mutation. However, there are important steps that can significantly reduce the risk of complications and improve quality of life for people with HHT.

Early diagnosis is the most important preventive measure. When HHT is identified early, screening tests can detect AVMs in the lungs, brain, and other organs before they cause serious problems^[5][9]. Finding these malformations when they are still asymptomatic allows for preventive treatment that can avoid life-threatening events like strokes or brain bleeds.

For individuals with known HHT or a family history of the condition, regular screening is essential. Adults with confirmed or suspected HHT should undergo screening for pulmonary AVMs using a test called transthoracic contrast echocardiography, with re-screening recommended every five years^[3][8]. Screening for brain AVMs using magnetic resonance imaging (MRI) is also recommended for adults and should be performed in the first six months of life for children with HHT^[8].

Managing nosebleeds proactively can help prevent the development of severe anaemia. This includes keeping the nasal passages moist using humidifiers, applying moisturising ointments or gels, and avoiding activities that might trigger bleeding, such as picking or forcefully blowing the nose^[9]. Staying well-hydrated and avoiding dry environments when possible can also help.

For individuals with documented pulmonary AVMs, taking antibiotics before dental procedures, endoscopies, or other medical interventions that might introduce bacteria into the bloodstream is crucial. This antibiotic prophylaxis helps prevent serious infections that could reach the brain through the abnormal blood vessels^[8][16]. Additionally, people with lung AVMs should ensure that air filters are used on all intravenous lines to prevent air bubbles from entering the bloodstream, and they should avoid scuba diving due to the risk of decompression sickness^[8].

Regular monitoring for iron deficiency and anaemia is important, especially for those experiencing frequent nosebleeds or gastrointestinal bleeding. Annual measurement of haemoglobin or haematocrit levels is recommended for all patients over age 35^[8]. When anaemia develops, iron supplementation through diet alone is often insufficient, and iron tablets or intravenous iron replacement may be necessary^[6][15].

Women with HHT who are pregnant or planning pregnancy should receive specialised care, as pregnancy carries additional risks including a slightly increased chance of major bleeding or stroke^[6][15]. Informing healthcare providers about HHT status before pregnancy allows for appropriate monitoring and management throughout gestation and delivery.

How the Body’s Normal Functions Are Affected

To understand how HHT affects the body, it helps to first understand how blood normally circulates. In a healthy circulatory system, the heart pumps oxygen-rich blood into arteries at high pressure. This pressure helps push blood through progressively smaller vessels called arterioles, and eventually into tiny vessels called capillaries^[2]. Capillaries are the smallest blood vessels in the body, and they serve crucial functions: they allow oxygen and nutrients to pass from the blood into surrounding tissues, they permit waste products to move from tissues back into the blood, and they act as natural filters for the bloodstream.

By the time blood reaches the capillaries, the pressure has decreased significantly. Blood then flows from capillaries into veins, which are thin-walled vessels designed to carry blood at low pressure back to the heart. This gradual transition from high-pressure arteries to low-pressure veins, mediated by the capillary network, is essential for normal circulation^[2].

In HHT, some blood vessels develop abnormally. Instead of arteries connecting to capillaries, which then connect to veins, abnormal direct connections form between arteries and veins. These abnormal connections are the arteriovenous malformations that define HHT^[2][4]. When these direct connections are small and occur near the skin surface, they are visible as telangiectases—those characteristic red spots. When they are larger and deeper, affecting internal organs, they are called AVMs.

Without the normal buffer of capillaries between them, blood rushes directly from high-pressure arteries into thin-walled, less elastic veins. This places enormous strain on the vein walls, causing them to become enlarged and distorted over time^[2]. The abnormal vessels are fragile and prone to rupture, which explains why bleeding is such a common problem in HHT.

The absence of capillaries in these malformations also means that blood bypasses the normal filtering and gas exchange functions. In the lungs, this is particularly problematic. Normally, as blood passes through lung capillaries, it picks up oxygen and releases carbon dioxide. The tiny capillaries also trap small particles, bacteria, and tiny blood clots, preventing them from travelling elsewhere in the body. When pulmonary AVMs allow blood to bypass these capillaries, oxygen levels in the blood may drop, and dangerous materials can pass through unfiltered, potentially reaching the brain and causing serious complications^[7][21].

The underlying cause of these abnormal blood vessel formations relates to the proteins that are missing or defective due to the genetic mutations. Endoglin and ALK1 are part of a signalling system that responds to growth factors, particularly one called BMP9 (bone morphogenetic protein 9). This signalling pathway helps regulate how blood vessels form, mature, and maintain their structure^[13]. When the pathway does not function properly due to mutations in HHT, endothelial cells receive incorrect signals about how to organise themselves and form blood vessels.

Research has also shown that people with HHT have elevated levels of another signalling molecule called VEGF (vascular endothelial growth factor), which promotes the growth of new blood vessels^[8][13]. The imbalance between defective BMP signalling and excessive VEGF activity contributes to the formation of abnormal vessels that characterise HHT.

AVMs can grow larger over time, and the abnormal blood flow through them can affect surrounding tissues. In the liver, extensive AVMs can create so much abnormal blood flow that the heart must work much harder to keep up with circulation demands, potentially leading to high-output heart failure. In the brain, AVMs can compress adjacent brain tissue, cause headaches or seizures, or suddenly rupture and bleed, causing strokes^[1].

The chronic blood loss from nosebleeds and gastrointestinal bleeding leads to iron deficiency anaemia in approximately half of adult patients with HHT^[20]. When the body loses blood repeatedly, it depletes its iron stores, which are necessary to make haemoglobin, the protein in red blood cells that carries oxygen. Without adequate haemoglobin, tissues throughout the body receive insufficient oxygen, leading to fatigue, weakness, shortness of breath, and reduced quality of life^[1].