Hereditary angioedema (HAE) is a rare genetic condition that causes sudden swelling attacks. Swelling can happen in the skin, stomach and intestines, genitals, throat, or upper airway.

HAE is caused by a gene change that affects how the body controls swelling. The gene change is often inherited, although some people with HAE have no family history of the condition.

Understanding what causes HAE can help you make sense of your diagnosis and what it might mean for you and your family.

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How Is HAE Inherited?

HAE often runs in families, but not always. There are two ways a person can develop HAE.

HAE With Family History

Most people with HAE get the gene change from one parent. When a parent has this gene change, each child has a 50 percent chance of getting it, too. However, this doesn’t mean every child in the family will have HAE.

HAE Without Family History

In about 1 out of 4 HAE cases, the person doesn’t have a parent with a gene change that causes HAE. Instead, the gene change happens on its own. These are called de novo gene variants. They can happen before birth or before pregnancy begins, when the egg or sperm is forming.

How Does HAE Cause Swelling?

The gene change that causes HAE affects a specific protein that controls swelling in the body. Here’s how it works:

• The SERPING1 gene is found on chromosome 11. It gives the body instructions for making a protein called C1 inhibitor (C1INH).
• C1INH controls swelling. It works by blocking proteins in the blood that cause inflammation. It also helps regulate immune system responses.
• When C1INH is missing or doesn’t work properly, a substance called bradykinin can build up in the bloodstream. Bradykinin leads to the swelling in an HAE attack.

It’s not clear why HAE swelling happens in attacks instead of all the time. Researchers also don’t know why swelling affects different parts of the body during different attacks. Studies into the underlying causes of HAE are ongoing.

Types of HAE

There are several types of HAE. Each type affects C1INH levels or how well C1INH works.

HAE With C1INH Deficiency

The most common type of HAE is type 1 HAE, also called HAE with C1INH deficiency. In this type, the body doesn’t make enough C1INH.

Without enough C1INH, bradykinin can build up and cause swelling attacks in places such as your arms, legs, face, and gastrointestinal tract.

HAE Without C1INH Deficiency

In HAE without C1INH deficiency, such as type 2 HAE, a person has normal or high levels of C1INH. However, C1INH doesn’t work properly.

A test can show how well C1INH is working and help diagnose type 2 HAE. When C1INH doesn’t work properly, bradykinin can build up in the bloodstream and cause HAE attacks.

In type 3 HAE, also called HAE with normal C1INH, a person has normal levels of C1INH, and it works the right way. But they still have swelling that does not get better with antihistamines or corticosteroids.

Researchers are still studying what causes HAE with normal C1INH. Types 1, 2, and 3 HAE all involve too much bradykinin. The main difference is why bradykinin builds up. C1INH may be missing, may not work the right way, or another issue may cause the body to make too much bradykinin.

What Can Set Off HAE Attacks?

If HAE is caused by a gene change, you may wonder why swelling attacks happen only sometimes. The answer isn’t always clear. Some attacks happen after a trigger. Others happen for no clear reason.

Triggers don’t cause HAE itself. Instead, they may set off swelling attacks in people who already have HAE. Common triggers include:

• Emotional stress
• Physical activities
• Illness or viral infections
• Pressure or injury
• Surgery or dental procedures
• Hormone changes
• Certain medications — These may include ACE inhibitors and birth control that contains estrogen.

Learning your possible triggers may help you and your doctor make a plan. For example, your doctor may suggest preventive treatment before surgery or dental work.

Talk to Your Doctor

Your HAE specialist can help you understand the specific gene change causing your HAE and what it means for your health and your family members.

Here are a few topics to talk about:

• Genetic testing — This can identify the exact gene variant responsible for your HAE and help determine inheritance patterns.
• Genetic counseling — If you’re planning a family or have children who may be at risk, a genetic counselor can help you understand what the results mean.
• Your HAE type — Knowing whether you have type 1, type 2, or type 3 HAE can affect treatment decisions.

⚠️ When To Seek Emergency Care

Upper airway swelling occurs in about 1 percent to 3 percent of HAE attacks — but when it does, it can be life-threatening. Get emergency medical care right away if you have:

• Severe swelling in your throat or airway
• Trouble swallowing
• Trouble breathing

Get emergency care even if you have already used your on-demand HAE treatment.

Join the Conversation

On myHAEteam, people share their experiences with hereditary angioedema, get advice, and find support from others who understand.

What are some of your known hereditary angioedema triggers? Let others know in the comments below.