Diagnosing hereditary haemorrhagic telangiectasia often begins when someone notices frequent nosebleeds or small red spots on their skin—but these seemingly minor signs can point to a complex genetic condition affecting blood vessels throughout the body.

Introduction: Who Should Undergo Diagnostics

If you experience frequent, unexplained nosebleeds that seem to happen for no clear reason, or if you notice delicate red or purple spots appearing on your lips, fingertips, or inside your mouth, it may be time to talk to your doctor about hereditary haemorrhagic telangiectasia. This condition, also known as HHT or Osler-Weber-Rendu syndrome, is a genetic disorder that affects blood vessels, causing them to form incorrectly^[1].

Because HHT runs in families, anyone who has a parent, sibling, or child diagnosed with the condition should consider getting tested, even if they feel perfectly healthy. The disorder is passed from parents to children, and if one of your parents has HHT, there is a 50 percent chance you will inherit it too^[4]. Many people with HHT do not realize they have it, and symptoms can vary greatly from one person to another, even within the same family^[1].

Children whose parents have HHT should be evaluated early in life. While some symptoms may not appear until later, early diagnosis can help prevent serious complications. Many clinical features of HHT develop over time, so what seems like a mild case in childhood might become more apparent in the teenage years or adulthood^[3].

It is also advisable to seek diagnostics if you experience symptoms such as shortness of breath, headaches, seizures, or unexplained fatigue, especially if you also have the more common signs like nosebleeds or red spots. These could indicate that abnormal blood vessels have formed in your lungs, brain, or other internal organs^[1].

Classic Diagnostic Methods

Most people with HHT are diagnosed based on clinical information rather than laboratory tests. Your healthcare provider will start by asking detailed questions about your personal medical history and your family’s health background, particularly focusing on parents, siblings, and children. They will also perform a physical examination, looking carefully at your skin, lips, tongue, and inside your mouth for the characteristic small red spots called telangiectases^[4].

The diagnosis of HHT is typically made using a set of criteria known as the Curaçao criteria. These criteria include four key features: recurrent nosebleeds (epistaxis), visible telangiectases in characteristic locations, abnormal blood vessel connections in internal organs (called arteriovenous malformations or AVMs), and a first-degree relative diagnosed with HHT^[3]. If you meet three or more of these criteria, your doctor can make a definite diagnosis of HHT. If you meet only two criteria, the diagnosis is considered possible^[8].

However, these clinical criteria have limitations, especially in children. Because many of the symptoms of HHT develop gradually over time, younger people may not yet show enough signs to meet the full criteria, even if they have inherited the condition. For this reason, children of a parent with HHT should be considered to have the disease unless it is ruled out by genetic testing^[8].

Genetic testing can provide a definitive diagnosis. HHT is caused by changes, called mutations, in certain genes that provide instructions for making proteins found in the lining of blood vessels. The most common genetic causes involve two genes: ENG (causing HHT type 1) and ACVRL1 (causing HHT type 2). A third gene, SMAD4, can also cause HHT, sometimes combined with other conditions^[2]. If a genetic test identifies one of these mutations, the diagnosis is confirmed even if clinical symptoms are not yet fully developed^[3].

Imaging Tests for Internal Organs

Because HHT can affect blood vessels in internal organs such as the lungs, brain, and liver, your doctor will likely recommend imaging tests to look for AVMs in these areas. These abnormal connections between arteries and veins can cause serious complications if left untreated, so finding them early is crucial^[9].

For the lungs, the initial screening test is usually a transthoracic contrast echocardiography, also called a bubble study. During this test, a healthcare professional places a small tube into a vein and injects a tiny amount of air bubbles. These bubbles help the doctor see whether abnormal blood vessels are present in the lungs^[8][9]. This test is recommended for all patients with confirmed or suspected HHT because lung AVMs occur in about 15 to 30 percent of people with the condition^[8].

To check for AVMs in the brain, doctors use magnetic resonance imaging (MRI). This scan creates detailed pictures of the brain and can detect abnormal blood vessels. For adults, the MRI is usually done with and without a contrast agent (a special dye) to maximize the chance of finding any problems. For children, an unenhanced MRI is typically performed in the first six months of life or at the time of diagnosis^[8]. Cerebral AVMs are present in more than 10 percent of patients with HHT^[8].

Other imaging tests may include ultrasound to examine the liver, CT scans to confirm lung or liver AVMs, and additional MRI scans to check other organs in the abdomen^[9]. These tests are painless and help doctors understand the full extent of the condition in each individual patient.

Monitoring for Anaemia

Because frequent nosebleeds and gastrointestinal bleeding are common in HHT, many patients develop anaemia, a condition where the body does not have enough red blood cells to carry oxygen effectively. Doctors recommend that all patients older than 35 years have their blood tested annually to measure haemoglobin or haematocrit levels, which indicate whether anaemia is present^[8]. If anaemia is detected, treatment with iron supplements or other interventions may be needed.

Diagnostics for Clinical Trial Qualification

When patients with HHT are being considered for enrollment in clinical trials, specific diagnostic tests are used to ensure they meet the study criteria and to establish baseline measurements for monitoring treatment effects. The exact tests required depend on the nature of the clinical trial, but several standard assessments are commonly used.

Genetic testing is often a key requirement for clinical trial qualification. Many trials seek to enroll patients with specific genetic mutations, such as those in the ENG or ACVRL1 genes. Identifying the exact genetic cause helps researchers understand how different mutations might respond to experimental treatments^[3].

Imaging studies are typically performed to document the presence and extent of AVMs before treatment begins. For trials focusing on lung AVMs, transthoracic contrast echocardiography or chest CT scans may be required to measure the size and location of these abnormal vessels^[8]. Similarly, trials investigating treatments for liver or brain involvement will require MRI or ultrasound imaging to establish a baseline before any intervention.

Blood tests are another standard component of clinical trial screening. In addition to genetic analysis, these may include complete blood counts to assess for anaemia, liver function tests, and measurements of iron levels (ferritin). Some trials may also measure specific proteins or markers in the blood that are related to blood vessel growth or function^[3].

For trials testing treatments aimed at reducing nosebleeds or gastrointestinal bleeding, patients may be asked to complete bleeding severity questionnaires or keep diaries documenting the frequency and duration of bleeding episodes. These tools help researchers measure whether the experimental treatment is having an effect compared to baseline levels.

Additional screening may include tests to evaluate organ function. For example, pulmonary function tests might be used to assess lung capacity and oxygen levels in patients with pulmonary AVMs. Cardiac evaluations, including echocardiograms, may be needed to check for signs of heart strain related to liver AVMs^[3].

All these diagnostic procedures help researchers select appropriate candidates for clinical trials and provide a way to measure whether new treatments are safe and effective. Patients interested in participating in clinical trials should discuss with their healthcare provider which tests they may need to undergo as part of the screening process.