Pathophysiology of fragile x syndrome in female

Fragile x syndrome is one of the genetic diseases everyone ought to know.  FXS is the most commonly known cause of inherited intellectual disability.

As the name implies, FXS when looked at through a microscope, part of the X chromosome looks “broken” or “fragile.”

It affects both males and females. Females often have milder symptoms than males. That is largely because males experience both greater frequency and greater severity of symptoms.

However, females with FXS do present a variety of challenges as well so this special expanded column is dedicated to addressing them.

This disorder is said to occur in approximately 1 in 4,000 males and 1 in 8,000 females. Other names include Fra(X) syndrome FRAXA syndrome, Martin-Bell syndrome, and X-linked mental retardation and macroorchidism.

The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. X-linked dominant means that in females (who have two X chromosomes), a mutation in one of the two copies of a gene in each cell is sufficient to cause the disorder.

In males (who have only one X chromosome), a mutation in the only copy of a gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females.

FXS is not life-threatening and although there is no cure, medication and therapy can help manage the symptoms.

Pathophysiology of Fragile X syndrome

Mutations in the FMR1 gene cause fragile X syndrome. FMR1 is a gene located on the X chromosome that produces a protein called FMRP needed for proper cell function.

The syndrome became known as the fragile X syndrome because some individuals with the disorder were found to have a segment of their X chromosome that appeared to be broken or fragile as earlier stated.

Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes.

Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome Xq27.3” refers to band 27.3 on the long arm of the X chromosome where the FMR1 gene is located.

It is the absence or severe reduction of the protein made by the FMR1 gene, FMRP, that causes fragile X syndrome. Mutation of the FMR1 gene causes the loss or reduction of FMRP.

Normally, this DNA segment is repeated from 5 to about 40 times. In people with fragile X syndrome, however, the CGG segment is repeated more than 200 times.

The abnormally expanded CGG segment turns off (silences) the FMR1 gene, which prevents the gene from producing FMRP.

Loss or a shortage (deficiency) of this protein disrupts nervous system functions and leads to the signs and symptoms of fragile X syndrome.

Males and females with 55 to 200 repeats of the CGG segment are said to have an FMR1 gene premutation.

Most people with this premutation are intellectually normal. In some cases, however, individuals with a premutation have lower than normal amounts of FMRP.

As a result, they may have mild versions of the physical features seen in fragile X syndrome (such as prominent ears) and may experience emotional problems such as anxiety or depression.

Signs and symptoms of fragile x syndrome

Let’s take a look at the different symptoms of this disorder. However, it is essential to note that the signs and symptoms are not limited to the ones listed below;

  • A large forehead
  • A large jaw
  • A long, narrow face
  • Anxiety
  • Attention-deficit/hyperactivity disorder (ADHD)
  • Depression
  • Difficulty picking up “social cues.”
  • Enlarged testicles (in males, after puberty)
  • Flapping or biting their hands
  • Flat feet
  • Language processing
  • Large ears and crossed/lazy eyes
  • Learning disabilities
  • Low intelligence quotient (IQ)
  • Low muscle tone
  • Obesity
  • Obsessive-compulsive behaviors
  • Poor eye contact
  • Problems with math
  • Seizures (epilepsy)
  • Self-injury behaviors
  • Sensory disorders
  • Social anxiety, shyness
  • Soft skin
  • Very flexible or double-jointed fingers

FAQs about fragile x syndrome

Below are the perfect answers to the most asked question about FXS;

Is fragile X syndrome permanent?

Yes. It’s a permanent disorder that lasts for a lifetime.

Can my child attend daycare/school?

Your child may need special accommodations at daycare or school. Some parts of the school day and classroom may need to be adjusted to fit their needs.

Does fragile X syndrome get worse with age?

The intelligence quotient (IQ) of a person with fragile X syndrome decreases over time. They become less intelligent with age.

What’s the life expectancy for someone with fragile X syndrome?

None of the symptoms of fragile X syndrome are life-threatening, so the life expectancy for someone with fragile X syndrome is the same as for the average person.

How do I help my friend or family member with fragile X syndrome?

Educate yourself as much as possible. Look for support groups and community resources that can help you and them. Life skills programs may be appropriate.

When should I take my child to see a healthcare provider?

Take your child in to see their pediatrician as soon as you notice the symptoms of fragile X syndrome. Don’t wait, as early intervention is important.

What questions should I ask a healthcare provider about my child’s fragile X syndrome?

The following are some questions you may want to ask the healthcare provider when you discuss your child’s diagnosis:

  • What therapists should my child see?
  • How severe is the fragile X syndrome?
  • What medications are appropriate for my child?
  • What are my early intervention options?

What’s the difference between fragile X and autism?

Fragile x syndrome can sometimes cause autism. If your child has autism, they have a 2% to 6% chance of also having fragile X syndrome.

Is fragile X syndrome hereditary?

Yes, fragile X syndrome is an inherited genetic condition.

Is fragile X syndrome only in males?

No, but males are more likely to have fragile X syndrome than females. Their symptoms are also more severe.

At what age are kids usually diagnosed with fragile X syndrome?

Boys are usually diagnosed around 35 to 37 months old, and girls around 42 months. You might start to notice symptoms in your child as early as 12 months.

Which healthcare providers evaluate and diagnose fragile X syndrome?

Your pediatrician or genetic counselor can order a test for fragile X syndrome.