Fragile X Carrier: Carrier Testing for Fragile X Syndrome in 2018

What is Fragile X? What is a carrier? And, most importantly, what is a Fragile X carrier and why is it so important to get tested?

Let’s back up a whole lot, genetically speaking, and then bring it all back to Fragile X carrier and testing for it and the importance.

Fragile X syndrome is a genetic disorder or condition that causes intellectual difficulties and struggles with learning as well as behavior. Kids with the syndrome struggle to understand as well as process information, which means that these kids have a difficult time with learning, behavior, and development. Fragile X gene, or Fragile X Mutation, is the most common cause of inherited intellectual disability andit is also known to be the most common cause behind inherited autism.

The syndrome affects more boys (approximately 1 in every 3,600 to 4,000 boys) than girls (approximately 1 in every 4,000 to 6,000 girls), and it also affects boys with more severity, meaning that male children have much worse symptoms. Also, Fragile X syndrome is equally distributed among cultures, meaning it appears in children of all cultures and genetic backgrounds equally.

Cognitive and Behavioral Symptoms

Cognitive and Behavioral Symptoms

Fragile X syndrome is not always obvious to spot based on physical appearance and, most of all, it varies from child to child. However, there are some common characteristics that are observed among all affected kids. These include prominent ears, a long and narrow face, poor muscle tone, flat feet, and loose joints that are a lot more flexible than usual. In terms of cognitive signs, intellectual disability and delays in development are the most common Fragile X features and many affected kids also have a hard time with fine and gross motor skills as well as delayed speech development.

In terms of behavior, observable differences or delayed development can be apparent in affected kids. Some of the typical signs include attention deficit hyperactivity disorder (ADHD), characteristics of autism spectrum disorder, shyness and/or anxiety that are particularly apparent in new situations, sensitivity to touch or loud noises, repetitive speech, difficulty with making eye contact and aggression. Some medical concerns with Fragile X syndrome children include ear infections, heart murmurs, reflux, seizures, and vision issues.

Genetics of Fragile X Syndrome

Fragile X syndrome is a genetic disorder, which means that it is caused by a genetic mutation. It is the result of a genetic mutation that is referred to as fragile X mental retardation 1 (FMR1) on the X chromosome. Most commonly, this mutation is an increase in the number of CGG trinucleotide repeats. More specifically, the disease appears to have four different forms depending on the number of the repeats of CGG in a gene. Those who have fewer than 45 CGG repeats are said to have a normal FMR1 gene, those with 45–55 CGG repeats have an “intermediate” allele, a mutation of 55–200 repeats is considered a permutation (the term permutation is used because the disease begins with a permutation that then expands to a full mutation in the coming generations) or a carrier, and if someone has more than 200 repeats of CGG, also referred to as the ‘full mutation,’ that person will suffer from intellectual disability and the aforementioned cognitive as well as behavioral symptoms. Only the full mutation will cause the FMR1 gene to shut down and stop producing the FMRP protein and the lack of this protein leads to symptoms of Fragile X syndrome.

What does it mean to be a Fragile X mutation carrier?

So, let’s get back to the carrier aspect of things. It is said that “one child is born every week with the syndrome and 20 are born with the carrier gene every week,” which means that there are a lot more carriers than there are those with actual obvious symptoms. So, who is actually considered to be a carrier? As mentioned above, any individual who has anywhere between 55 and 200 repeats of CGG in their FMR1 gene on the X chromosome is considered to be a ‘carrier.’ This means that they have a permutation or an unstable mutation that has the potential to expand in future generations and therefore cause Fragile X syndrome in their kids or grandkids. One specific feature of diseases such as Fragile X syndrome is that the genes can change size during the process of passing it on. Over the generations, the gene can change sizes and as such become more unstable and can, therefore, occur more frequently and/or severely in the following generations.

Fragile X Carrier Testing

Why get tested if you are a carrier and do not exhibit any symptoms? Well, would it not be of help to know what kind of genetic disorders you may pass on to your kids and/or grandkids? There are three circumstances around which individuals should get tested with carrier screening. These include having clinical symptoms that suggest Fragile X syndrome, (2) having a family history of the disorder, intellectual or learning disabilities or autism of unknown cause or infertility, and (3) either family or personal history of Fragile X.

DNA analysis of an individual’s sample can be as accurate as 99%, which means there’s a way to know for sure whether you are a carrier or not. Given that Fragile X is an X chromosome disorder, male carriers can only pass it on to their daughters while female carriers can pass it on to both sons as well as daughters. The inheritance is dominant, meaning that only one copy of the mutation is enough to have symptoms. Since males have only one X chromosome, if inherited, they will be affected for sure and more severely.

Ultimately, carrier screening is a fairly quick procedure and knowing early on may significantly increase a kid’s chances of overcoming the symptoms of Fragile X. With awareness having increased over the years, there are methods of teaching kids to help them advance and live normal lives.

Laura Day
 

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