Friedreich ataxia Carrier Screening (Genetic Testing) Overview

What is Friedreich Ataxia?

Friedreich ataxia (FRDA) is a condition characterized by problems with balance and coordination (ataxia). It is caused by harmful genetic changes (variants) in the FXN gene. The FXN gene helps to incorporate iron into specific proteins within a part of the cell called the mitochondria. Harmful changes in the FXN gene lead to the inability to make these iron-dependent proteins correctly. As a result, the mitochondria cannot produce enough energy; instead, iron builds up and causes damage.

The early symptoms of FRDA include problems with balance, control of the arms, and difficulty with speech. Individuals may also develop heart problems, poor bladder control, muscle weakness, scoliosis (abnormal curvature of the spine), vision and hearing problems, and diabetes. FRDA may impact verbal fluency, attention, memory, and processing speed of information. Depression may also be more common in individuals with FRDA.

The most common type of Friedreich ataxia is the classic form of the condition, in which symptoms begin before age 25. Approximately 25% of individuals with FRDA will have an atypical type with a later onset and less severe symptoms. Progression of the disease may be slower in later onset forms.

How is Friedreich Ataxia inherited?

The inheritance of Friedreich ataxia is more complex than many other genetic diseases. A healthcare professional, such as a genetic counselor, can help answer questions about this condition and the risk of transmitting it to the next generation.

Friedreich ataxia is among a group of diseases called "trinucleotide repeat disorders." These diseases are caused by a sequence of DNA (GAA) that is repeated over and over in the same gene. While everyone has these repeats, the number of repeats determines whether or not a person has the disease or can pass it on to future generations.

All individuals inherit one copy of the FXN gene from each parent. Expansions of the GAA repeat on both copies of the FXN gene cause most cases of FRDA. A small number of cases of FRDA are caused by other harmful changes in the FXN gene that are not GAA repeat expansions.

Each copy of the FXN gene can be categorized into the following groupings depending on the number of GAA repeats:

If both parents carry at least one copy of the gene that falls into the premutation, borderline, or full expansion category, they have a chance of having a child with Friedreich ataxia.

Normal repeat length

An FXN gene with 5 to 33 GAA repeats is considered normal. GAA repeats in this range are considered stable because they usually pass from parent to child with the same number of repeats. Individuals with this number of repeats on both gene copies do not have an increased chance of having a child with Friedreich ataxia caused by GAA repeat expansion.

Premutation repeat length

An FXN gene with 34 to 65 GAA repeats is considered a premutation. Each time a premutation passes from parent to child, the number of GAA repeats can increase or decrease. Therefore, if a parent has a copy of the FXN gene with 34-65 repeats, it is possible that this copy will be passed to the child and that the number of repeats may increase to a full expansion. Smaller premutations, from 34-43, are unlikely to cause symptoms if the other copy of the gene has a full expansion and are less likely to increase to a full expansion when passed from parent to child. Larger premutations, from 44-65 repeats, are considered borderline repeats and are described below.

Borderline repeat length

An FXN gene with 44 to 65 GAA repeats is considered borderline. A copy of the gene with a borderline repeat may become a full expansion when passed from parent to child. Individuals with a borderline repeat on both copies of the FXN gene or a borderline repeat and a full expansion may experience symptoms of FRDA later in life (over age 40), but the severity and age of onset are difficult to predict.

Full expansion repeat length

An FXN gene with over 65 repeats is considered a full expansion. If a child inherits two copies of the FXN gene (one from each parent) with a full expansion, they are expected to develop symptoms of Friedreich ataxia. However, in rare instances, individuals who inherit a full expansion from both parents do not develop symptoms or develop a later onset form of the disorder.

How common is Friedreich Ataxia?

The incidence in the population is approximately 1 in 15,000 to 1 in 40,000 live births.

How is Friedreich Ataxia treated?

There is no cure for Friedreich ataxia. Treatment is based on the symptoms of the disease. Treatment may include physical and occupational therapy, walking aids or wheelchairs for mobility, speech therapy for communication, diet modification for swallowing issues, treatment of cardiac disease depending on symptoms, insulin therapy for diabetes, medication for bladder dysfunction, hearing or visual aids, and psychosocial support. Recently, the FDA approved a drug that can improve the symptoms of Friedreich ataxia called omaveloxolone (brand name Skyclarys) for individuals 16 and older.

What is the prognosis for a person with Friedreich Ataxia?

The prognosis for FRDA depends on when symptoms develop and how severe they are. The condition is progressive, meaning symptoms become more severe with time. Typically, affected individuals require a wheelchair for mobility approximately ten years after symptoms begin. The average life expectancy for those with the classic form condition is in the 30s.

Benefits of Friedreich ataxia Carrier Screening (Genetic Testing)

Carrier screening is an important form of genetic testing for those who may be at risk of passing friedreich ataxia to their baby. Carrier Screening for friedreich ataxia can help in identifying that risk. The Foresight^® Carrier Screen helps clinicians guide care and empowers patients to take action to make the best decision for their families. Learn more about the Foresight^® Carrier Screen} by Myriad Genetics.