Fragile X syndrome (FXS)

What is Fragile X syndrome?
SIMPLIFIED EXPLANATION

Autistic people are more likely than others to have Fragile X syndrome (FXS). It's a genetic difference. In general, people who have fragile x syndrome need a lot of support. This can result in individuals having a particular type of facial appearance, but you would have to be familiar with the condition to notice this difference.

Photo courtesy of Kathy Pozer

What is Fragile X syndrome?

It’s a series of mutations found on the X chromosome, one of the human sex chromosomes. People with Fragile X syndrome have a distinctive face, a different intellectual development and an attention deficit. Everyone has at least one X chromosome. However, people with a single X chromosome and the associated syndrome (mostly boys and men) need a lot of support.

Link to autism

4% of autistic people have Fragile X syndrome (Hjalmarsson, L., 2020).
4%
15 to 25% of people with Fragile X syndrome are autistic.
20%

Symptoms

Potential for adaptation

How do you become a person with Fragile X syndrome?

Fragile X syndrome is hereditary. In other words, it is transmitted from parent to child. The syndrome is transmitted via the X sex chromosome. People born female generally have two X chromosomes (XX). Those born male usually have one X and one Y chromosome (XY). Since everyone has an X chromosome, both girls and boys can have the syndrome. However, the symptoms will be different.

To find out more
WHAT'S DIFFERENT ABOUT THE X CHROMOSOME?

Chromosomes are like big libraries inside our cells. Chromosomes contain a large number of genes. Genes are like recipe books. Genes contain the instructions for creating the proteins that make up our bodies. The recipes are written in a special alphabet called DNA, which contains just 4 letters: A, T, C and G.

Fragile X syndrome occurs when a mistake is made in the FMR1 gene. The FMR1 gene contains a particularly complicated recipe for cells to read. Although each person is different, and therefore the recipes written in their genes are different, the recipe for the FMR1 gene always begins in the same way: the letters CGG repeated between 3 and 54 times. The FMR1 gene is a difficult recipe for cells to read because of the repetitions at the beginning, which make it harder for the cells to read the recipe as a whole.

In the case of Fragile X syndrome, it's as if there's been a "misprint" of the FMR1 recipe. The letters CGG are repeated over 200 times! The cells can no longer understand the recipe. The cells still create the protein, but without having understood all the instructions.

In short, Fragile X syndrome occurs when the FMR1 recipe on the X chromosome can no longer be read by our body's cells.

Fun fact

Fragile X syndrome is so called because the X chromosome appears to be on the verge of breaking where the FMR1 gene is located.

Photo courtesy of Kathy Pozer

Fragile X syndrome in people born male (XY)

People with Fragile X syndrome who are born male tend to have more symptoms and more needs than those born female. Chromosomes contain the genes that are our body’s recipe books. People born as boys have only one X chromosome, so they only have one copy of each gene and each recipe present on that chromosome. If a recipe is missing or badly written, the body can’t re-invent it and will have to make do without it! For this reason, people born male with the syndrome will have more impaired intellectual development, a peculiar face with elongated features and protruding ears, and generally more severe symptoms than people born female with the same syndrome. In addition, male people born with Fragile X will need a great deal of support.

Fragile X syndrome in people born female (XX)

People with Fragile X syndrome have very different profiles. Generally speaking, they have fewer symptoms than those born male, because they have two copies of the X chromosome, i.e. two copies of each recipe. Cells can therefore “compare recipes”. However, the bodies of people born with two X chromosomes (XX) will deactivate one copy of the X chromosome before birth. This is an extremely important mechanism, because the X chromosome contains the recipes for essential proteins that must be produced in a precise quantity. If the body kept two copies active, the cells would produce twice as many proteins!

Photo courtesy of Kim Villeneuve

When the X chromosome is deactivated

Sometimes, the body will deactivate the fragile X chromosome. These people will have almost no symptoms of the syndrome. The recipe containing the error is never consulted by the cells after birth.

When only the X chromosome is active

Sometimes, the body will keep only the fragile X chromosome active. These people will have more severe symptoms, since the recipes contained in this chromosome will be the first to be consulted by the cells after birth. For these people, the symptoms of Fragile X syndrome will be more severe.

Mosaic presentation

Sometimes, the body will let the cells choose. So each cell will choose its preferred X chromosome. This is called a mosaic presentation. In these cases, symptoms vary greatly from one person to the next. It depends on the percentage of cells that have chosen the fragile X. Generally speaking, people born as girls with a mosaic presentation will experience symptoms of anxiety. They’ll feel as if they’re always having to compensate and pretend to be like everyone else, when in fact something in their bodies works differently.

For find out more

Some people think that the Fragile X gene, FMR1, is dominant, i.e. it's a gene that expresses itself by default. For example, the brown-eye gene is dominant; it's the gene that expresses itself all the time if it's there, and suppresses the others. Blue-eyed people don't have the gene for brown eyes. However, the FMR1 gene is not dominant. The FMR1 gene has the same strength as other genes.

Are Fragile X syndrome and autism the same thing?

No, Fragile X syndrome and autism are not the same thing. Some traits are common to both conditions, such as being easily overwhelmed sensorially or fearing social activities. But many traits are unique to Fragile X syndrome, such as the shape of the face or the great difficulty in solving equations. And other traits are unique to autism, such as communication difficulties that occur even when the person knows the language. As described at the beginning of this text, people with autism can also have Fragile X syndrome. And conversely, people with Fragile X syndrome can also be autistic.

“But I read a study that said they had found a cure for autism by studying Fragile X syndrome”

In November 2022, a group of American researchers published a study on autism claiming to use the animal model of autism to better understand differences in the nervous system. To do this, they transmitted the FMR1 gene with a misprint to mice. As we saw earlier in this text, a misprint in the FMR1 gene is what causes Fragile X syndrome. So, they bred mice with the animal version of Fragile X syndrome to study autism.

And if that seems to not make any sense, that’s because it doesn’t!

Researchers say that Fragile X syndrome is the leading genetic cause of autism, since 25% of people with Fragile X are also autistic. However, many people with neurodivergence such as Fragile X syndrome, autism, ADHD or dyslexia have associated conditions. For example, 30% of people with autism also have ADHD. But we can’t study autism to find drugs to help people with ADHD!

Nonetheless, this study provides some interesting insights into Fragile X syndrome in mice and perhaps in humans. Mice with Fragile X syndrome are hyposensitive, even though they are more easily overwhelmed sensorially. The reasons for this contradiction are still in need of investigation.

Catherine Bouchard-Tremblay

Science popularizer