Overview

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare genetic disorder that affects blood vessels. Individuals with HHT develop abnormal blood vessel formations, called telangiectasias and arteriovenous malformations (AVMs), which can cause frequent bleeding and complications in various organs. The condition is inherited in an autosomal dominant pattern, meaning a child has a 50% chance of inheriting the disorder if one parent is affected. HHT is a lifelong condition, but early diagnosis and treatment can help manage symptoms and reduce complications.

Causes

HHT is caused by mutations in certain genes that are crucial for the development and maintenance of blood vessels. The most commonly affected genes include:

• ENG gene: Mutation in this gene leads to HHT type 1, often associated with pulmonary and brain AVMs.
• ACVRL1 (ALK1) gene: Mutation causes HHT type 2, more commonly linked to liver AVMs.
• SMAD4 gene: Mutation can cause a combined syndrome of HHT and juvenile polyposis, a condition that involves intestinal polyps.

These genetic mutations lead to fragile blood vessels that are prone to rupture, causing frequent bleeding and AVM-related complications in various organs.

Symptoms

Symptoms of HHT can vary widely among individuals, even within the same family. Common symptoms include:

• Nosebleeds: Frequent and spontaneous nosebleeds (epistaxis) are often the first noticeable symptom, starting in childhood or adolescence.
• Telangiectasias: Small, red or purple spots visible on the skin and mucous membranes, especially on the lips, tongue, face, and fingertips.
• Gastrointestinal bleeding: Telangiectasias in the stomach or intestines can cause chronic or sudden gastrointestinal bleeding, leading to anemia.
• Arteriovenous malformations (AVMs): Abnormal connections between arteries and veins can occur in the lungs, brain, liver, or spine, sometimes leading to serious complications like stroke, heart failure, or brain abscess.
• Fatigue: Often a result of chronic blood loss and anemia.
• Shortness of breath: Due to AVMs in the lungs causing low oxygen levels.

Diagnosis

The diagnosis of HHT is based on clinical criteria and genetic testing:

• Clinical criteria (Curaçao Criteria): Diagnosis is considered definite if three of the following four are present:
  • Spontaneous and recurrent nosebleeds.
  • Telangiectasias at characteristic sites.
  • AVMs in internal organs (lungs, liver, brain).
  • Family history of HHT.
• Imaging studies: CT scans, MRI, or ultrasound are used to detect AVMs in internal organs.
• Echocardiogram with bubble study: To detect pulmonary AVMs and assess right-to-left shunting.
• Genetic testing: Confirms the diagnosis by identifying mutations in ENG, ACVRL1, or SMAD4 genes.

Treatment

There is no cure for HHT, but treatments focus on managing symptoms and preventing complications:

• Nosebleed management: Humidification, nasal ointments, laser therapy, and in severe cases, surgical interventions like septodermoplasty.
• Iron supplements and transfusions: To manage anemia caused by chronic bleeding.
• Endoscopic treatment: Gastrointestinal telangiectasias can be treated with endoscopic laser coagulation or argon plasma coagulation.
• Embolization: Pulmonary AVMs can often be treated with catheter-based embolization to block abnormal vessels.
• Neurosurgical or radiological interventions: For brain AVMs to reduce the risk of stroke or bleeding.
• Liver AVMs: Monitored regularly; in severe cases, medications or liver transplantation may be considered.
• Anti-angiogenic medications: Drugs like bevacizumab are being studied and used in certain cases to reduce bleeding frequency.

Prognosis

The prognosis for individuals with HHT varies depending on the severity of symptoms and organ involvement:

• Improved outcomes with early care: With proper screening and treatment, most people with HHT can manage symptoms and avoid life-threatening complications.
• Lifelong monitoring: Regular follow-up care, including screening for AVMs and managing bleeding, is crucial.
• Normal life expectancy: Many individuals with well-managed HHT live a normal lifespan, although those with severe AVMs may have increased health risks.
• Quality of life: While the condition can be disruptive, especially with frequent nosebleeds, symptom control can lead to significant improvements in daily functioning.

Early diagnosis, multidisciplinary care, and regular monitoring can greatly improve quality of life and outcomes for individuals living with hereditary hemorrhagic telangiectasia.