Hereditary Hemorrhagic Telangiectasia (HHT): Symptom, Causes, Treatment

What are the symptoms of hereditary hemorrhagic telangiectasia?

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare genetic disorder that affects the blood vessels, causing abnormal formation of tiny blood vessels, known as telangiectases, in the skin, mucous membranes, and other organs. The symptoms of HHT can vary in severity and may not appear until adulthood. Here are some common symptoms of HHT:

Cutaneous manifestations:

1. Telangiectases: Small, reddish-blue spots or patches on the skin, often on the face, nose, lips, hands, and feet.
2. Pulsating or bulging telangiectases: In some cases, the telangiectases can become enlarged and pulsate or bulge due to increased blood flow.
3. Epistaxis (nosebleeds): Frequent and recurring nosebleeds are a hallmark symptom of HHT.

Internal manifestations:

1. Gastrointestinal telangiectases: Abnormal blood vessels can develop in the digestive tract, leading to bleeding, iron deficiency anemia, and abdominal pain.
2. Pulmonary arteriovenous malformations (PAVMs): Abnormal connections between arteries and veins in the lungs can cause shortness of breath, chest pain, and bleeding.
3. Brain lesions: Arteriovenous malformations (AVMs) in the brain can lead to seizures, headaches, stroke-like symptoms, and cognitive impairment.
4. Cardiac complications: AVMs in the heart can cause arrhythmias, heart failure, and sudden death.

Other symptoms:

1. Migraines: Many people with HHT experience frequent migraines or other types of headaches.
2. Fatigue: Recurring bleeding episodes can lead to iron deficiency anemia, which can cause fatigue.
3. Gastrointestinal issues: Abdominal pain, diarrhea, or constipation may occur due to gastrointestinal telangiectases.
4. Shortness of breath: Pulmonary AVMs can cause chronic respiratory problems.

Important notes:

• HHT symptoms can vary widely in severity and may not be present until adulthood.
• Diagnosis is often delayed or misdiagnosed due to the rarity of the condition.
• A multidisciplinary approach involving specialists from cardiology, pulmonology, gastroenterology, neurology, and dermatology is essential for accurate diagnosis and treatment.

If you suspect you or a family member may have HHT, consult a healthcare provider for a proper evaluation and diagnosis.

What are the causes of hereditary hemorrhagic telangiectasia?

Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder caused by mutations in genes that play a crucial role in the development and maintenance of blood vessels. The primary causes of HHT are mutations in three main genes:

1. ENG (Endoglin) gene: The most common cause of HHT, accounting for about 70-80% of cases. The ENG gene provides instructions for making a protein called endoglin, which is involved in the development and maturation of blood vessels.
2. ALK1 (Activin Receptor-Like Kinase 1) gene: Responsible for about 20-30% of HHT cases. The ALK1 gene codes for a protein that plays a crucial role in the regulation of angiogenesis (the formation of new blood vessels) and vasculogenesis (the formation of blood vessels from embryonic precursors).
3. SMAD4 gene: A rare cause of HHT, accounting for about 5% of cases. The SMAD4 gene is involved in the transmission of signals from receptors on the surface of cells to the nucleus, where they regulate gene expression.

These genetic mutations lead to abnormalities in blood vessel development and maintenance, resulting in the characteristic telangiectases and AVMs found in HHT. The specific mechanisms by which these mutations cause HHT are not fully understood, but they may include:

• Abnormalities in blood vessel development and maturation
• Increased permeability of blood vessels, leading to leakage and bleeding
• Defects in the regulation of angiogenesis and vasculogenesis
• Disruption of normal blood flow patterns and pressure gradients

Inheritance patterns:

• Autosomal dominant inheritance: In this pattern, a single copy of the mutated gene is enough to cause the condition. If one parent has HHT, each child has a 50% chance of inheriting the mutated gene.
• Sporadic mutations: In some cases, HHT may occur without a family history of the condition due to spontaneous mutations.

Understanding the genetic causes of HHT is crucial for accurate diagnosis, counseling, and genetic testing. If you or a family member has been diagnosed with HHT, it’s essential to consult with a genetic counselor or a healthcare provider to discuss genetic testing options and risk assessments for other family members.

How is the diagnosis of hereditary hemorrhagic telangiectasia made?

The diagnosis of Hereditary Hemorrhagic Telangiectasia (HHT) is made by a multidisciplinary team of healthcare providers, typically involving a combination of medical history, physical examination, imaging studies, and genetic testing. The diagnosis involves identifying the characteristic symptoms and signs of HHT, as well as ruling out other potential causes of similar symptoms. Here’s a step-by-step approach to diagnosing HHT:

1. Medical history: A detailed medical history is essential to identify the characteristic symptoms of HHT, including:
   • Recurring nosebleeds (epistaxis)
   • Skin telangiectases
   • Migraines or headaches
   • Gastrointestinal bleeding or iron deficiency anemia
   • Pulmonary or cerebral symptoms (in some cases)
2. Physical examination: A thorough physical examination should be performed to look for:
   • Telangiectases on the skin and mucous membranes
   • Signs of iron deficiency anemia (pallor, koilonychia, etc.)
   • Abnormal blood vessels or murmurs on cardiac examination
3. Imaging studies:
   • Echocardiogram: To evaluate the heart and pulmonary blood vessels
   • Magnetic Resonance Angiography (MRA): To visualize the brain and spinal cord vasculature
   • Computed Tomography Angiography (CTA): To evaluate pulmonary and gastrointestinal vasculature
   • Gastrointestinal endoscopy: To evaluate the gastrointestinal tract for telangiectases and bleeding
4. Genetic testing:
   • Molecular genetic testing: Analysis of the ENG, ALK1, and SMAD4 genes to identify mutations associated with HHT
   • Linkage analysis: To determine if a family member is a carrier of a mutation if they do not have symptoms themselves
5. Other diagnostic criteria:
   • The Curaçao Criteria: A set of diagnostic criteria that include:
     • Recurring epistaxis (nosebleeds)
     • Telangiectases in multiple generations
     • Other characteristic features (e.g., migraine, gastrointestinal bleeding, etc.)
6. Specialized testing:
   • Pulmonary function tests: To assess lung function and detect potential lung involvement
   • Neuroimaging studies: To evaluate potential brain or spinal cord involvement

A definitive diagnosis of HHT requires a combination of clinical, imaging, and genetic findings. In some cases, the diagnosis may be suspected based on family history and clinical presentation, but genetic testing may be necessary to confirm the diagnosis.

It’s essential to consult with a multidisciplinary team of healthcare providers, including specialists in cardiology, pulmonology, gastroenterology, neurology, and genetics, to ensure accurate diagnosis and comprehensive management of HHT.