Understanding Fragile X Syndrome

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Meet Mike Tozer, the “Suitman”. He hopes to set a Guinness World Record time for running a half-marathon in a suit. But he has an ulterior motive. . . to raise awareness of, and funds for, Fragile X syndrome, a genetic condition that affects his son.

Fragile X syndrome (FXS) is a genetic disorder that causes cognitive and developmental disability. It is something the counselors at Recombine talk about often. Daily? Maybe not. Weekly? Definitely. It’s just that common.

FXS is one of the trickier genetic conditions to address. On the surface, it follows a straight enough pattern of inheritance: X linked recessive. This means that, though girls can be affected if they inherit a mutation, it is more commonly seen in boys. Why? Girls should have two sex chromosomes – and X and an X, one from each of their parents. So if one of the X chromosomes has a mutation the other X chromosome can, in a sense, work as a back up. Males should have two sex chromosome – an X and a Y. They get the X from mom and the Y from dad. So if they inherit an X with a mutation, there is no backup to work in its place.

Simple, right? Not so much.

Many other factors go into whether or not a woman who has a mutation will actually have an affected son. The two I will briefly touch upon are: (1) mutation size and (2) AGG repeats.

Think of a rubber band. Now, write the word “Fragile X” on that band. Ninety-nine percent of the time, when a person has Fragile X, it is because the gene has expanded, making it hard to read. So, if you hold the rubber band at rest between two fingers, you can still read the words “Fragile X”. Now, stretch it a bit. The words are still readable, but are now more and more stretched, making the word harder to read. What if you continue to stretch the rubber band? Then the words get even harder to read and the health or integrity of the rubber band may be somewhat affected after time.

The take home message: the more you stretch the band, the more likely it is that it will have issues working correctly. Same with the Fragile X gene.

So is there anything that can protect the integrity of the band? Yes. AGG repeats.

Think of these like those sections that are built into roads right before bridges. They are safeguards that increase the stability of the road and adjust for expansion during hot and cold weather. In the same sense, the AGG repeats stabilize the Fragile X gene, making it less likely to expand. We want those repeats and the more the better.

Testing at Recombine not only looks at the overall size of a woman’s two Fragile X genes, but also, we complete AGG repeat analysis if we find that a gene falls into a larger size category. This helps us provide a patient with a more accurate risk assessment regarding the chance that their gene will get larger and thus of having a child with Fragile X syndrome.

To learn more about Fragile X, please visit the National Fragile X Foundation website!

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About Author

Shannon Wieloch

Shannon Wieloch is a licensed board-certified genetic counselor at Recombine. Her primary responsibility is to provide genetic counseling to Recombine patients. She is also the current co-chair of the National Society of Genetic Counselors Prenatal Special Interest Group. Prior to joining Recombine, Shannon worked in cardiac research at The Children's Hospital of Philadelphia and in prenatal genetic counseling at The Delaware Center for Maternal and Fetal Medicine. She received a dual B.S. in biology and psychology from The University of Pittsburgh and her M.S. in genetic counseling from Arcadia University. Her passion is to provide comprehensive genetic education to medical professionals, patients and the general public.