The causes of hereditary haemorrhagic telangiectasia (HHT) lie in inherited genetic mutations that disrupt normal blood vessel development and repair.
This rare disorder comes from a faulty gene passed down by one parent. Just one altered gene copy is enough to cause HHT. Knowing what causes hereditary haemorrhagic telangiectasia helps doctors improve testing, guide families, and create better long-term care plans.
At the core, HHT is a blood vessel disorder. In healthy people, tiny capillaries connect arteries to veins. In people with HHT, these capillaries don’t form properly. Instead, arteries link directly to veins. These connections—called arteriovenous malformations (AVMs)—are fragile and can bleed or burst easily.
Key Genes Linked to HHT
Most HHT cases come from mutations in one of three specific genes.
a) ENG (Endoglin)
ENG mutations cause about 40–60% of HHT cases. The ENG gene makes a protein that helps control how blood vessels grow. It works through a system called the TGF-β pathway.
When the ENG gene doesn’t work right, new blood vessels form in the wrong way. This leads to tiny red or purple spots on the skin and sometimes large AVMs in the lungs or brain.
This type is known as HHT type 1. It often starts earlier and causes more severe symptoms, like shortness of breath or even strokes caused by blood clots bypassing the lungs.
b) ACVRL1 (also called ALK1)
This gene is faulty in about 30–50% of people with HHT. Like ENG, it helps keep blood vessels strong. If ACVRL1 is damaged, abnormal vessels can form.
This form is called HHT type 2. It often shows up later and may cause AVMs in the liver. These liver AVMs can stress the heart, especially in older adults.
c) SMAD4
This gene is rarely involved, but when it is, the condition looks different. People with SMAD4 mutations often have both HHT and another condition called juvenile polyposis. This combination raises the risk of digestive tract bleeding and colon cancer.
These patients may have nosebleeds and AVMs, but also polyps in the gut, low iron levels, and bleeding from the bowel. They need regular checks of both their blood vessels and digestive system.
Other Possible Genetic Causes
In some people—around 5–10%—no known gene mutation is found. These cases might involve unknown genes or parts of DNA that control how genes are turned on and off.
Researchers are still working to find these missing links. Some genes may also act as modifiers. This means they can change how bad the disease is, even in people with the same main mutation.
This could explain why symptoms vary so much within the same family. One person might have mild nosebleeds, while another may need treatment for serious AVMs.
Hepatitis A and Genetic Research
While Hepatitis A and HHT are very different, both show the value of genetic research. In Hepatitis A, genes influence how the liver responds to the virus. In HHT, gene mutations shape how blood vessels form. Understanding these genes gives doctors tools to act early and avoid harm.
How the Disease Develops
No matter which gene is at fault, the result is the same: blood vessels don’t form correctly. The small structures that normally connect arteries to veins are missing or weak.
As a result, blood vessels may:
- Stretch or widen too much
- Let blood skip the capillary stage
- Bleed easily, even without injury
In the lungs or brain, these problems can cause serious issues. Blood may pass through without picking up oxygen. Clots can also travel to the brain, causing strokes or infections.
Frequent bleeding, especially from the nose or gut, may lead to long-term iron loss. This can cause tiredness, weakness, and poor quality of life.
How HHT Is Passed Down
HHT runs in families in a clear pattern. If one parent has HHT, each child has a 50% chance of inheriting it. Both boys and girls can be affected. The condition does not skip generations.
But not everyone shows symptoms right away. Some relatives might carry the gene and not know it. This makes family testing very important.
Once a diagnosis is confirmed in one family member, others can be checked through genetic testing. If they carry the same mutation, doctors can start screening early and watch for hidden AVMs in the lungs or brain.
Early action, like with Hepatitis A, helps stop problems before they start.
Environmental and Lifestyle Factors
Although HHT comes from a gene change, outside factors can make symptoms worse.
For example:
- Hormonal changes in puberty or pregnancy may trigger more nosebleeds
- High blood pressure or injury may increase the risk of bleeding
- Chronic swelling or stress on the blood vessels can also have an impact
Some changes in gene expression—called epigenetics—might also play a role. These don’t change the DNA itself, but they affect how active a gene is. This could help explain why some people have severe HHT and others do not, even in the same family.
Doctors are studying this area to develop more targeted treatments.
In Summary
The causes of hereditary haemorrhagic telangiectasia include inherited changes in key genes like ENG, ACVRL1, and SMAD4. These mutations disrupt normal blood vessel formation and make vessels weak and prone to bleeding. Though the disease can’t yet be cured, understanding these causes allows for early diagnosis, family testing, and better care.
Like Hepatitis A, HHT shows the power of prevention, awareness, and personalised care in managing complex health conditions.
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