Heterozygous Familial Hypercholesterolemia: What to Know

Medically Reviewed By Megan Soliman, MD

Familial hypercholesterolemia (FH) is a genetic disorder that causes very high cholesterol. Heterozygous familial hypercholesterolemia (HeFH) means you have inherited the condition from one parent’s DNA. There are two primary types of FH: homozygous and heterozygous. Both types are caused by inheriting genetic variations for the condition from biological parents.

Homozygous familial hypercholesterolemia (HoFH) develops when both biological parents pass the genetic variations on to a child.

Heterozygous familial hypercholesterolemia (HeFH) develops when only one biological parent passes on the genetic variations to the child.

This article discusses HeFH, how it differs from HoFH, its symptoms, causes, treatment, and outlook.

Key facts about HeFH

  • HeFH is a hereditary genetic condition that causes very high cholesterol levels.
  • Often, doctors diagnose HeFH after a cholesterol test, as it doesn’t cause any noticeable symptoms.
  • Treatment for HeFH includes taking medications as well as self-care.
  • HeFH can increase the risk of other cardiovascular diseases, but treatment can help lower chances.

Homozygous vs. heterozygous familial hypercholesterolemia

HoFH is the more severe form Trusted Source AHA/ASA Journals Peer reviewed journal Go to source of familial hypercholesterolemia (FH). It occurs when you inherit genetic variations from both parents. 

HoFH causes extremely high levels of low-density lipoprotein (LDL) cholesterol — about 400 milligrams per deciliter (mg/dL) Trusted Source American Heart Association Highly respected national organization Go to source of blood or higher. This can start at a very young age. Without treatment, you may develop heart disease by 10 years old, and sometimes as early as 2 or 3 years old. 

By contrast, HeFH is when you inherit the genetic variations from only one parent. It is more common than HoFH, affecting about 1 in 200 Trusted Source AHA/ASA Journals Peer reviewed journal Go to source people worldwide.

If you have HeFH, your LDL cholesterol will be over 190 mg/dL Trusted Source American Heart Association Highly respected national organization Go to source of blood for adults, or 160 mg/dL Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source for children. However, you may not have symptoms or know you have the condition. 

Still, if you do not receive treatment, you have a higher risk of developing early-onset heart disease. Sometimes, heart disease due to HeFH develops from 30 years old. 

Read more about familial hypercholesterolemia.

Symptoms of heterozygous familial hypercholesterolemia

HeFH often has no noticeable symptoms Trusted Source AHA/ASA Journals Peer reviewed journal Go to source . Unless you know you inherited a genetic variation for HeFH or take a blood cholesterol test, you may not know you have it.

It is more common to develop physical symptoms if you have HoFH. Still, you may develop Trusted Source American Heart Association Highly respected national organization Go to source some of these symptoms with HeFH, such as:

  • yellowish cholesterol deposits in or around the eyes
  • gray or white rings around the eye’s cornea
  • smooth and firm bumps in the elbows, hands, knees, or back of the ankle

When to see a doctor

If you have a biological family member with HeFH, ask a doctor for screening for yourself. This may include checking for high cholesterol or cardiovascular disease.

Early diagnosis and treatment are vital for reducing the risk of complications. Often, the symptoms of HeFH do not appear until complications develop. 

Contact a doctor promptly if you have any symptoms of FH or cardiovascular disease, such as:

Also, call 911 if you have symptoms of heart attack or stroke.

Diagnosing heterozygous familial hypercholesterolemia

Diagnosing HeFH can involve a combination of:

  • physical exams
  • blood tests
  • genetic testing — also known as genetic counseling

These tests can check blood cholesterol levels and look for genetic variations related to FH. In some cases, doctors may use other diagnostic procedures, such as imaging scans of the heart, to rule out other conditions or identify complications.

Doctors will also ask about your personal and family medical histories.

Genetic counseling is key for HeFH because it can alert close biological family members to get tested. Close biological family members can include:

  • parents
  • children
  • siblings
  • grandparents
  • aunts and uncles
  • nieces and nephews
  • cousins

Children at high risk for FH should begin getting regular screenings for high cholesterol at 2 years old Trusted Source American Heart Association Highly respected national organization Go to source . Talk with a doctor about when children should get tests.

Causes and inheritance of heterozygous familial hypercholesterolemia

Cholesterol comes from food, and the liver produces it as a byproduct. LDL cholesterol, which builds up with HeFH, is also known as “bad” cholesterol because it can cause cardiovascular disease.

HeFH usually occurs Trusted Source AHA/ASA Journals Peer reviewed journal Go to source due to variations or mutations in the genes responsible for the LDL cholesterol receptor in cells. These receptors help cells use or remove LDL from the body. 

Variations in other genes that help LDL cholesterol bind to the receptor or break down can also cause HeFH.

These genetic variations mean the body cannot effectively remove LDL cholesterol from the bloodstream, causing it to build up.

Inheritance

HeFH is inherited in an autosomal dominant way. This means that if one out of the two biological parents carries HeFH genetic variations, each child they have together has a 1 in 2 Trusted Source Centers for Disease Control and Prevention (CDC) Governmental authority Go to source chance, or 50% probability, of developing HeFH.

Your other chances of developing HeFH are:

  • 1 in 4 if the following biological family members have the genetic variations:
    • half-siblings
    • aunts and uncles
    • grandparents
  • 1 in 8 if the following biological family members have the genetic variations:
    • cousins
    • other relatives

Around 1 in 500 people carry a genetic variation that can cause HeFH.  

Risk factors for heterozygous familial hypercholesterolemia

The primary risk factor for HeFH is having a biological parent with a genetic variation for the condition.

Still, several other factors can worsen the condition if it develops, such as:

  • eating a diet high in saturated fats
  • having overweight or obesity
  • not getting enough physical activity
  • smoking
  • experiencing high levels of stress
  • not getting enough good quality sleep
  • having a high alcohol intake
  • having certain medical conditions, such as diabetes, sleep apnea, or chronic kidney disease
  • taking certain medications
  • being over 40 years old

Treatment for heterozygous familial hypercholesterolemia

The most common HeFH treatment is statin medications to lower cholesterol levels. 

Other treatment approaches include:

Learn more about statins and other cholesterol medications.

If you have severe HeFH, your medical team may recommend LDL apheresis to physically remove cholesterol from the blood.

LDL apheresis works by using a needle and catheter to remove small amounts of blood and circulate them through a machine that filters out LDL. The filtered blood returns to the body through an intravenous line into a vein.  

Complications of heterozygous familial hypercholesterolemia

The primary risk of HeFH is cardiovascular disease. High cholesterol levels can cause the arteries to thicken or harden, known as atherosclerosis. Atherosclerosis can lead to cardiovascular disease by blocking blood flow.

Without effective treatment, HeFH leads to a 30% to 50% chance Trusted Source AHA/ASA Journals Peer reviewed journal Go to source of experiencing a cardiac event by the time you are 50 or 60 years old. Cardiac events include any conditions that damage the heart muscle or circulatory system, such as:

These cardiac events are sometimes fatal.

Outlook of heterozygous familial hypercholesterolemia

The outlook of HeFH can vary per person and depend on accurate diagnosis and treatment.

With advances in research and treatment strategies, the outlook for HeFH can be positive.

Previously, medical experts claimed that people with HeFH had a life expectancy of about 20 to 30 years Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source less than people without HeFH.

A 2022 study Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source reported that people with HeFH may still have a lower life expectancy. However, overall, researchers suggested that life expectancies for people with HeFH have improved.

Among 813 participants, the mean age of death for people with HeFH was 69.3 years old, compared to 73.5 years old for people without FH.

The reviewers from the 2022 study suggest improvements in life expectancy are due to an earlier diagnosis and improved treatment plans.

Talk with your medical team if you have any questions about HeFH outlook or treatment.

Summary

HeFH is a hereditary genetic disorder that causes very high cholesterol levels. This can increase the risk of cardiovascular diseases, such as heart attack or stroke.

Usually, HeFH doesn’t cause noticeable symptoms. As a result, cholesterol testing is essential in children and close biological family members of people with HeFH to diagnose the condition before it causes complications.

Treatment for HeFH can include medications, lifestyle approaches, and LDL apheresis.

Talk with a doctor if you have questions about HeFH or heart health.

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Medical Reviewer: Megan Soliman, MD
Last Review Date: 2024 Apr 15
View All Cholesterol Articles
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