FXTAS is a genetic disorder which means that it is an inherited disease. The abnormal gene responsible for this disease is passed along from generation to generation by family members who carry it. Genetic diseases like FXTAS occur when one of the body’s 20,000 genes does not work properly. Genes are microscopic structures within the cells of our bodies that contain instructions for every feature a person inherits from his or her parents.  

FXTAS is an X-linked disorder, meaning that the mutated gene is found on the X chromosome called FMR1. Since males only have one X chromosome, they are more likely to develop X-linked disorder like FXTAS.  

Females can also develop FXTAS, but they usually have milder symptoms since they have two X chromosomes. Since females have two X chromosomes, all cells in their body will randomly “turn off” one copy of the X chromosome through a process call x-inactivation. Research suggests that if most cells in a woman’s body have turned off the X chromosome containing an FMR1 mutation, she will have no symptoms or mild symptoms. However, if the X chromosome containing an FMR1 mutation is turned on, the woman will have more severe symptoms. More research is being done to better understand FXTAS symptoms in women.  

FXTAS is caused by a mutation called a CGG triplet repeat expansion in the FMR1 gene. The number of repeats you have influences your risk of developing FXTAS or other Fragile X disorders.  

• Between 55-40 CGG Repeats: This is the typical number of repeats in the FMR1 gene. People with this number of repeats are usually healthy. 

• Between 55-200 CGG Repeats: This length of repeats is called an FMR1 gene premutation. People with the FMR1 gene premutation are more likely to develop FXTAS or Fragile X-Associated Primary Ovarian Insufficiency (FXPOI). However, some people with the FMR1 gene premutation will develop FXTAS and/or FXPOI, while others do not. Researchers are trying to better understand the variability in why some people develop symptoms and others do not.  

• Over 200 CGG Repeats: People with more than 200 repeats usually develop a condition called Fragile X Syndrome, which causes intellectual disability, behavioral difficulties, learning challenges, and various physical characteristics. Fragile X syndrome affects young children, mainly boys.  

Gene tests can be performed for diagnostic purposes to determine what kind of Ataxia is within a person or family. Genetic testing also can be done, in some circumstances, even before there are symptoms to determine whether a person carries the abnormal gene or genes that cause Ataxia. This is called predictive or presymptomatic testing. A gene test also can be used to determine whether a fetus has an abnormal Ataxia gene. This is called prenatal testing. Anyone who is considering a predictive or prenatal test should consult with a genetic counselor to discuss the reasons for the test, the possible outcomes, and how those outcomes might affect the person emotionally, medically, or socially.   

Since FXTAS, FXPOI, and Fragile X Syndrome are all caused by mutations in the FMR1 gene, a diagnosis in one family member can have implications for the whole family. If someone is diagnosed with FXTAS, their family members (particularly grandchildren) may want to consider genetic testing for Fragile X Syndrome. Likewise, if a child is diagnosed with Fragile X Syndrome, older family members may want to consider genetic testing for FXTAS or FXPOI.