What is Hereditary Hemorrhagic Telangiectasia?

Hereditary Hemorrhagic Telangiectasia (HHT, also known as Osler-Weber-Rendu Syndrome) is a complex disease involving malformed blood vessels that can impact multiple organ systems. HHT frequently goes undiagnosed and untreated, though it affects approximately 1 in 5,000 people. This inherited disorder affects both males and females of all ages and from all ethnic and racial backgrounds.

A variety of treatments exist for the various features of HHT to improve quality of life and prevent-life threatening complications. With appropriate treatment, individuals with HHT can expect a near-normal life expectancy.

The team of experts at UHealth has been named a HHT Center of Excellence by Cure HHT. 

Here at the University of Miami Health System, we provide a multidisciplinary approach with several experienced HHT physicians and staff in the departments of interventional radiology, genetics, gastroenterology, neurosurgery, hematology, ENT, dermatology, pulmonology and cardiology. As a patient, you will meet and work directly with Dr. Joseph Zikria, M.D., the founding medical director of the University of Miami HHT Center, and his HHT Clinical Coordinator Shannon Lange, where patients will receive comprehensive care for the diagnosis and management of the condition to help improve their quality of life and overall health.

What causes HHT?

HHT is caused by an autosomal dominant genetic mutation. There are different mutations in each of the three genes known to cause HHT. This condition does not skip a generation, and each child born to an HHT parent has a 50% chance of inheriting the genetic mutation.

Symptoms of HHT

The symptoms associated with HHT vary from person to person. People with HHT tend to form arteriovenous malformations (AVMs), which are blood vessels that lack normal capillaries between an artery and vein. Some manifestations of HHT, such as telangiectasias (dilated small blood vessels or small AVMs) cause nosebleeds. Other complications (like larger AVMs in the lungs, brain or liver) may not necessarily trigger any initial symptoms and can happen at any age, but may cause serious and life-threatening complications.

The following symptoms or events can occur in people without HHT, but a family history could indicate you have HHT.

• Spontaneous nosebleeds (epistaxis): experienced by up to 90% of adults with HHT
• Iron deficiency anemia (low iron in the blood)
• Telangiectasias are red dots that disappear when pushed on. They can appear on the skin (including the lips, tongue, mouth, hands and face) and/or in the gastrointestinal tract (which can cause bleeding)
• Larger AVMs that develop in the brain, lungs and/or liver
• Life-threatening complications from lung AVMs or brain VMs
• Shortness of breath
• Exercise intolerance
• Fatigue
• Migraine headaches
• Seizures
• Stroke
• Back pain, swelling or numbness
• Heart failure 

How is HHT diagnosed?

The Curaçao Diagnostic Criteria for HHT

The Curaçao Diagnostic Criteria reflect the typical signs of HHT and consider your family history. If you have at least three of these criteria, you are diagnosed with HHT. If you have two of these criteria, you probably have HHT. If you experience only one of these criteria, it is unlikely that you have HHT.

These criteria are less reliable in diagnosing young children because some of these symptoms do not present until late childhood or adulthood.

• Recurrent and spontaneous mild to severe nosebleeds (epistaxis)
• Multiple telangiectasia on the hands, lips, face or inside of the nose or mouth
• AVMs or telangiectasia in the lungs, brain, liver, intestines, stomach and/or spinal cord
• Family history of HHT (i.e., a first-degree relative who experiences at least three of these criteria or has been genetically diagnosed with HHT)

Genetic testing for HHT

There are hundreds of potential mutations in each of the three genes known to cause HHT. The goal of genetic testing is to identify the specific HHT gene mutation that causes HHT within your family and confirm a HHT diagnosis. This information can be used to help diagnose other members of your family (often children and young adults) who do not meet the clinical diagnostic criteria. Genetic testing can identify asymptomatic (without symptoms) HHT or rule out HHT in children in families with a known mutation.

• A positive genetic test confirms that you carry your family’s HHT gene mutation and that you have HHT.
• A negative genetic test means that you do not carry your family’s HHT gene mutation, and you did not inherit HHT. However, a negative genetic test does not always rule out HHT.
• 15% of people with HHT have genetic mutations that are not yet identified as HHT genes. Repeat testing in the future might be beneficial because more HHT-causing genes can be discovered.

Families are strongly encouraged to arrange genetic testing through a medical geneticist or genetic counselor who understands all of the complexities and limitations of genetic testing for HHT.