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Fragile X Syndrome

Fragile X Syndrome (FXS) is a relatively common genetic disorder that leads to features like intellectual disability, autism, a large jaw, and large ears. FXS arises from an X-linked dominant gene, which means it is a sex-linked trait. Sex-linked traits are more common and more severe in males (who have one X and one Y chromosomes) than females (who have two X-chromosomes). FXS was named after the way the way the affected X-chromosome looks broken, or fragile, in the exact region where the Fragile X gene (called the FMR1 gene) lies. The FMR1 gene codes for a protein that is important for brain development, and people with FXS lack this protein, which causes many of their symptoms.

Symptoms

Fragile X Syndrome is not a life-threatening condition, but it does have several physical symptoms, including:

  • Large chin
  • A long face
  • Large ears
  • Large testicles after puberty (in males)
  • Intellectual disabilities
  • Heart valve problems – dizziness, difficulty breathing, palpitations.
  • Abnormally flexible joints

FXS also has autism as a prominent symptom. Some features of this include:

  • Poor eye contact
  • Poor social skills
  • Repetitive behaviours
  • Obsession with certain objects
  • Not interested in interacting with others

Cause

FXS is the most common inherited cause of intellectual disability. FXS is passed down from family member to family member, via the X-chromosome.

FXS is caused by an error in the FMR1 gene on the X-chromosome, where a normal portion of the gene – called a nucleotide sequence – is improperly repeated over and over. This nucleotide sequence is CGG, and when abnormally repeated it leads to instability of the FMR1 gene. The unstable FMR1 gene cannot produce the protein that it should, and without these proteins normal brain development cannot occur. This leads to Fragile X Syndrome.

Risk Factors

There are no risk factors for Fragile X Syndrome that you can control. The risk factors that do exist are genetic, including:

  • Family history – Fragile X Syndrome is passed down genetically, from a parent to his/her kids. Sporadic (randomly occurring) Fragile X Syndrome is extremely rare. Less than 2% of people have sporadic FXS, while over 98% have inherited FXS.
  • Being male – Males have only one X chromosome so they will have FXS if they have one abnormal FMR1 gene. Females have two X chromosomes, so they may have one abnormal FMR1 gene and still not have FXS, because of their normal FMR1 gene on their other X-chromosome.

Diagnosis

Fragile X Syndrome is diagnosed with genetic testing, which requires DNA samples. This usually requires a blood test and can be done to an adult or a child. A DNA sample can even be gathered from a baby that is still in the womb (the uterus) while a woman is pregnant. These pre-natal (before birth) tests are done either with amniocentesis or chorionic villus sampling, which involve garnering cells from the amniotic fluid and the placenta, respectively.

Treatment

After Fragile X Syndrome is diagnosed, the treatment for it involves a wide range of medications and therapies. Fragile X Syndrome cannot be cured, but it can be well managed with these treatments.

Many of the medications given to people with FXS are for psychological problems, such as antidepressants or ADHD medication. Some other medicines that might be given are sleeping pills, or medicines that can reduce aggression or abnormal behaviour (called anti-psychotic medication).

If a person with FXS has a heart valve problem that becomes dangerous or severe, they may require surgery. Otherwise, their heart valve dysfunction can be managed with several types of medicine, including beta blockers (which reduce the stress on the heart) and anti-arrhythmic medicines (which make the heartbeat in a normal rhythm, reducing palpitations).

Therapy is one of the most important treatments of FXS, including speech therapy, behavioural therapy, and personalized educational help. Frequent therapy has been shown to improve the everyday life of people with Fragile X Syndrome.

 
 
 

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