Hereditary hemorrhagic telangiectasia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Hereditary hemorrhagic telangiectasia is a disorder that results in the development of multiple abnormalities in the blood vessels.

In the circulatory system, blood carrying oxygen from the lungs is normally pumped by the heart into the arteries at high pressure. The pressure allows the blood to make its way through the arteries to the smaller vessels (arterioles and capillaries) that supply oxygen to the body's tissues. By the time blood reaches the capillaries, the pressure is much lower. The blood then proceeds from the capillaries into veins, through which it eventually returns to the heart.

In hereditary hemorrhagic telangiectasia, some arterial vessels flow directly into veins rather than into the capillaries. These abnormalities are called arteriovenous malformations. When they occur in vessels near the surface of the skin, where they are visible as red markings, they are known as telangiectases (the singular is telangiectasia).

Without the normal buffer of the capillaries, the blood moves from the arteries at high pressure into the thinner walled, less elastic veins. The extra pressure tends to strain and enlarge these blood vessels, and may result in compression or irritation of adjacent tissues and frequent episodes of severe bleeding (hemorrhage). Nosebleeds are very common in people with hereditary hemorrhagic telangiectasia, and more serious problems may arise from hemorrhages in the brain, liver, lungs, or other organs.

There are several forms of hereditary hemorrhagic telangiectasia, distinguished mainly by their genetic cause but with some differences in patterns of signs and symptoms. People with type 1 tend to develop symptoms earlier than those with type 2, and are more likely to have blood vessel malformations in the lungs and brain. Type 2 and type 3 may be associated with a higher risk of liver involvement. Women are more likely than men to develop blood vessel malformations in the lungs with type 1, and are also at higher risk of liver involvement with both type 1 and type 2. Individuals with any form of hereditary hemorrhagic telangiectasia, however, can have any of these problems.

Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is a condition that involves both arteriovenous malformations and a tendency to develop growths (polyps) in the gastrointestinal tract. Hereditary hemorrhagic telangiectasia types 1, 2 and 3 do not appear to increase the likelihood of such polyps.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in several genes, including the ACVRL1, ENG, and SMAD4 genes, cause hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia type 1 is caused by mutations in the ENG gene. Type 2 is caused by mutations in the ACVRL1 gene. Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is caused by mutations in the SMAD4 gene. All these genes provide instructions for making proteins that are found in the lining of the blood vessels. These proteins interact with growth factors that control blood vessel development. Mutations in other genes, some of which have not been identified, account for other forms of hereditary hemorrhagic telangiectasia.

Mutations in these genes generally prevent the production of the associated protein or result in the production of a defective protein that cannot fulfill its function. An individual with a mutated gene will therefore have a reduced amount of the functional protein available in the tissue lining the blood vessels. This shortage is believed to result in the signs and symptoms of hereditary hemorrhagic telangiectasia.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The incidence of hereditary hemorrhagic telangiectasia is difficult to determine because the severity of symptoms can vary widely and some symptoms, such as frequent nosebleeds, are common in the general population. In addition, arteriovenous malformations may be associated with other medical conditions. Hereditary hemorrhagic telangiectasia is widely distributed, occurring in many ethnic groups around the world. It is believed to affect between 1 in 5,000 and 1 in 10,000 people.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Epistaxis · Very frequent (99-80%)

Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.

Lip telangiectasia · Very frequent (99-80%)

Telangiectasia (that is, the presence of small dilated superficial blood vessels) of the lips.

Mucosal telangiectasiae · Very frequent (99-80%)

Telangiectasia of the mucosa, the mucous membranes which are involved in absorption and secretion that line cavities that are exposed to the external environment and internal organs.

Nasal mucosa telangiectasia · Very frequent (99-80%)

Telangiectasia of the nasal mucosa.

Telangiectasia · Very frequent (99-80%)

Telangiectasias refer to small dilated blood vessels located near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. Telangiectasia are located especially on the tongue, lips, palate, fingers, face, conjunctiva, trunk, nail beds, and fingertips.

Telangiectasia of the skin · Very frequent (99-80%)

Presence of small, permanently dilated blood vessels near the surface of the skin, visible as small focal red lesions.

Tongue telangiectasia · Very frequent (99-80%)

Telangiectasia (that is, the presence of small dilated superficial blood vessels) of the tongue.

Spontaneous, recurrent epistaxis · Very frequent (99-80%)

Other findings in the same source

From: Orphanet

Additional reported features include Abnormality of cardiovascular system physiology (Frequent (79-30%)); Anemia (Frequent (79-30%)); Arteriovenous malformation (Frequent (79-30%)); Migraine (Frequent (79-30%)); Portal hypertension (Frequent (79-30%)); Pulmonary arteriovenous malformation (Frequent (79-30%)); Hepatic arteriovenous malformation (Frequent (79-30%)); Visceral angiomatosis (Frequent (79-30%)); Abnormality of the cerebral vasculature (Occasional (29-5%)); Cerebral arteriovenous malformation (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Hereditary hemorrhagic telangiectasia is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Hereditary hemorrhagic telangiectasia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.