I recently wrote a blog entry that was all about influencing the sex of your baby. All that talk about X and Y chromosomes prompted one of my patients to ask me about Fragile X syndrome. She had just been diagnosed as a carrier for this disorder and wanted me to help her sort through her options.

What is Fragile X Syndrome?

dreamstime_3346214Fragile X is a genetic disorder and is the most common cause of inherited mental impairment and cognitive problems including some forms of autism. It is caused by a mutation of the FMR1 gene on the X chromosome. The mutation turns off the production of the FMR1 protein which in turn affects brain development. People with Fragile X suffer from mental impairment which can take the form of anything from very minor learning difficulties to severe cognitive problems. They may be hyperactive or over sensitive to stimuli and they may have short attention spans. Physically people with Fragile X may have a long narrow face, prominent ears, enlarged testicles and loose joints. Approximately 1 in 2000 boys suffer some kind of mental impairment due to Fragile X. The disorder also affects girls but the incidence is lower and the symptoms tend to be milder. This is because girls have 2 copies of the X chromosome whereas boys only have one. This means that girls have 2 copies of the FMR1 gene so if one is mutated a girl has another copy of the gene to fall back on. Boys only have one X chromosome.

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

yinovablog621Fragile X syndrome is carried on the X chromosome. Since men (XY) and women (XX) each have at least one X chromosome, both parents can be carriers. If a father is a carrier, he can only pass the gene defect to his daughters, since he transmits a Y chromosome to his sons. All of his daughters will inherit the gene, but as far as anyone knows this inherited defect will be in the premutation stage which means that if a daughter inherits Fragile X from her father she will not be symptomatic although she can pass the disorder on to her children. yinovablog608If a mother is the carrier, she can pass the gene defect to either her sons or her daughters, since she contributes an X chromosome to each. If, as a woman, you are a carrier you have a 50% chance of passing the gene on because you have two X chromosomes and only one of them is affected. So if you are a carrier you may not pass on the defect at all or you may just pass on the premutation or your child could inherit the full syndrome. Sons who have fragile X are at high risk of intellectual disability but daughters who receive the fragile X gene may appear normal because the have two X chromosomes and only one is affected.

If you are a carrier how is risk assessed.

yinovablog614A simple blood test can establish if you are a carrier of Fragile X and the degree to which this mutation is likely to cause problems for your child. Geneticists classify the gene mutation into three categories based on the number of repeats of a pattern of DNA called CGG repeats. Individuals with less than 60 CGG repeats have a normal gene. Individuals with 60-200 CGG repeats have a premutation which means they do have a small risk of their child suffering from Fragile X syndrome and that risk is directly related to the number of CGG repeats. Parents with over 200 repeats have a full mutation which causes fragile X syndrome. dreamstime_1690719As for my patient. She fell into the middle ground in that she had the premutation and so was at a small risk of passing on Fragile X. Fortunately we live in a time when we have access to good genetic testing and advice. Her doctor was able to reassure her that, because the number of CGG repeats was low her risk of passing this disorder on to her child was minimal. An amniocentesis at 16 weeks was able to confirm her doctor’s prediction and she was relieved to hear that her baby was just fine. Although it’s scary to find out that you are a carrier for a genetic disorder such as Fragile X, it’s important to find out more about your own situation. You may find that with a combination of genetic and prenatal testing you , like my patient, receive reassuring news.
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