Friedreich Ataxia Inheritance and Genetics: What Families Should Know

Friedreich ataxia is an inherited form of ataxia. It is sometimes abbreviated as FA or FRDA and is caused by mutations, or changes, in the FXN gene. The main risk factor is having a relative with the condition. This article explains the genetics of Friedreich ataxia and how it is passed down in families.

What Causes Friedreich Ataxia?

Friedreich ataxia develops in people with mutations in the FXN gene. This gene provides instructions for making the frataxin protein. Researchers do not fully understand what frataxin does in cells, but they believe it helps protect mitochondria, the tiny organelles in our cells that make energy, by controlling iron levels.

If there’s too much iron in a cell, it leads to oxidative stress. This stress develops from harmful oxygen particles that damage cells and tissues. Frataxin stores extra iron and releases it when the body needs it. Without enough frataxin, oxidative stress may lead to the symptoms of Friedreich ataxia.

Friedreich Ataxia Develops From Repeats in DNA

Our DNA is made of four chemicals, known as bases:

• Adenine (A)
• Guanine (G)
• Thymine (T)
• Cytosine (C)

Humans have around 3 billion DNA bases that make up the genetic code. More than 99 percent of these bases are exactly the same in everyone. Small changes in these bases can lead to differences between people, including some diseases.

The FXN gene contains a piece of DNA called a GAA trinucleotide repeat. GAA is a pattern in the genetic code. In most people, this pattern repeats about five to 33 times in a row.

Friedreich ataxia develops in people who have too many GAA repeats in both copies of the FXN gene. They may have anywhere from 60 to more than 1,000 GAA repeats in a row. Studies show that the number of repeats you have can affect:

• How old you are when you develop symptoms of Friedreich ataxia
• How severe your symptoms are
• How quickly your disease progresses or worsens over time

For example, people with 66 to 300 GAA repeats typically develop symptoms after they turn 25. The longer the GAA repeats, the more severe your symptoms are. Most people with Friedreich ataxia have more than 100 GAA repeats in both copies of the FXN gene.

A small number of people develop Friedreich ataxia because of other changes in the FXN gene. According to the Friedreich’s Ataxia Research Alliance (FARA), around 4 percent of cases involve these mutations. A person with these changes usually has:

• One FXN gene with more than 100 GAA repeats
• One FXN gene with another type of mutation, such as a missing, extra, or changed DNA letter.

Mutations in the Frataxin Gene Lead to Friedreich Ataxia

If these repeats get too long, cells cannot make enough frataxin to work properly. Muscle and nerve cells need frataxin to work properly. Without enough frataxin, Friedreich ataxia develops. Mitochondria live in all of the body’s cells, including skeletal and heart muscle cells.

The brain sends messages through the spinal cord and nerves to the muscles. These messages tell the muscles to move so we can walk, talk, and eat. Low frataxin levels can lead to symptoms such as:

• Ataxia or difficulty walking
• Trouble with balancing and coordination
• Loss of touch or sensation, including issues with sensing pressure, temperature, and pain
• Scoliosis, an abnormal curve in the spine
• Heart problems, such as enlargement of the heart muscle
• Diabetes

How Is Friedreich Ataxia Passed Down Through Families?

Genes are passed down from parents to their children. Everyone inherits two copies of most genes — one from their mother and the other from their father. To develop Friedreich ataxia, you need to inherit two nonworking copies of the FXN gene. This is known as autosomal recessive inheritance. Friedreich ataxia affects males and females equally, and the risk depends on family history.

People who have one expanded copy of the FXN gene are known as carriers. They don’t develop Friedreich ataxia or have any symptoms. For a child to develop Friedreich ataxia, they need to have two parents who are carriers. Each parent then has to pass down an expanded copy of the gene.

Studies show that 1 out of every 100 people is a carrier for Friedreich ataxia. If a carrier has a child with another carrier, there’s a 25 percent chance their child develops Friedreich ataxia. There’s also a 75 percent chance their child does not develop this genetic disorder. Just because you’re a carrier, it doesn’t mean you’ll have a child with Friedreich ataxia.

Genetic Testing for Friedreich Ataxia

The only way to confirm a Friedreich ataxia diagnosis is with genetic testing. Several genetic tests can look for changes in the FXN gene. Doctors take a small blood sample to look for genetic changes.

Genetic testing is also appropriate for family members of people with Friedreich ataxia. If you’re related to someone with Friedreich ataxia, you can find out whether you’re a carrier. Knowing your carrier status helps you understand your chances of having children who may be affected.

Your healthcare provider may refer you to a genetic counselor. These professionals help people with genetic conditions understand what to expect after a diagnosis. Genetic counselors can connect you to specialists who treat Friedreich ataxia.

What Risk Factors Are Associated With Friedreich Ataxia?

The strongest risk factor for Friedreich ataxia is having a family history of the condition. However, a child develops Friedreich ataxia only if they inherit a nonworking FXN gene from both parents.

People of European Descent Are Most Likely To Develop Friedreich Ataxia

Ancestry plays a role in the risk of developing Friedreich ataxia. People with European ancestry are the most likely to develop this genetic disease. Other groups affected include those from South Asia, the Middle East, and Northern Africa.

The group affected the most by Friedreich ataxia is the Acadians. This group traces back to about 100 families who moved from France to eastern Canada in the 1600s. The Muscular Dystrophy Association (MDA) explains that 1 out of every 70 people of Acadian ancestry is a carrier for Friedreich ataxia.

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