Fragile X Syndrome: Causes, Symptoms, Diagnosis and Treatment

Fragile X syndrome (FXS), also known as Martin-Bell syndrome, is an inherited condition that causes developmental delays, intellectual disabilities, learning and behavioral issues, physical abnormalities, anxiety, attention-deficit/hyperactivity disorder and/or autism spectrum disorder, among other problems. It’s the most common form of inherited intellectual and developmental disability (IDD).

FXS is named fragile X syndrome because, when looked at through a microscope, part of the X chromosome looks “broken” or “fragile.”



FXS is one of three syndromes in the fragile X family. The other two syndromes are:

  • Fragile X-associated tremor/ataxia syndrome (FXTAS). Symptoms include balance problems, shaky hands, unstable mood, memory loss, cognitive problems and numbness in the hands and feet.
  • Fragile X-associated primary ovarian insufficiency (FXPOI). Symptoms include reduced fertility, infertility, missing or unpredictable menstrual periods and premature menopause.

Can you die from fragile X syndrome?

No. The symptoms of fragile X syndrome are not life-threatening.

How common is fragile X syndrome? How often does fragile X syndrome occur?

Although the exact number isn’t clear, researchers estimate that, worldwide, about 1 in 8,000 to 11,000 females and 1 in 4,000 to 7,000 males have fragile X syndrome.

Experts don’t know for sure how many people carry the fragile X premutation, which can be passed down to their child and cause fragile X. Some studies estimate that, in the United States, 1 in 148 to 291 women and 1 in 290 to 855 men have the premutation. Parents with the premutation are nearly two times more likely to have a child with a disability than those without the premutation.

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.

Are carriers of fragile X at risk of any health problems?

Yes. If your child has fragile X syndrome, you should tell your primary healthcare provider. As a possible carrier, you’re at a higher risk for:

Menopause that starts before age 40 (females only).

  • Dementia.
  • High blood pressure.
  • Depression.
  • Anxiety.
  • Migraines.
  • Hypothyroidism.
  • Chronic pain.
  • Sleep apnea.

Fragile X syndrome gets passed from parent to child. A DNA part called the “CGG triplet repeat” expands within a gene called “FMR1,” producing a mutation that causes fragile X syndrome. A normal part repeats five to 40 times, but in people with fragile X syndrome it repeats more than 200 times. That “silences” the FMR1 gene, stopping it from producing an important protein called “FMRP” (fragile X mental retardation protein). This messes up the nervous system and causes the symptoms of fragile X syndrome.

There are four classifications of the fragile X mutation. They’re determined by the number of times the CGG repeats in the DNA:

  • Normal.
  • Gray zone.
  • Premutation carrier.
  • Full mutation.

Not everyone with the mutated FMR1 gene has FXS symptoms. Some people are still able to make the FMRP protein because:

  • They’re female. Females are not as likely to get FXS.
  • The size of the mutation is small.
  • They have mosaicism. This is where some cells have the FMR1 mutation and others don’t.

What are the symptoms of fragile X syndrome?

Fragile X syndrome affects your child’s intelligence, mental health, physical features and behavior. Common symptoms in each category include:

Intelligence issues:

  • Learning disabilities.
  • Low intelligence quotient (IQ). Their IQ scores decrease with age.
  • Delayed early developmental milestones. Milestones are social/emotional, language/communication, cognitive (thinking, learning, problem-solving) as well as movement/physical development (see below).
  • Delayed development of nonverbal communication such as using gestures, body language and facial expressions.
  • Problems with math.
  • Language processing. You might notice that your child struggles with speech and language around age two.

Talk to your child’s healthcare provider about exactly what milestones to watch out for and how to evaluate them.

Mental health problems:

  • Anxiety.
  • Depression.
  • Obsessive compulsive behaviors.

Physical features:

  • A long, narrow face.
  • A large forehead.
  • A large jaw.
  • Soft skin.
  • Large ears and crossed/lazy eyes.
  • Very flexible or double-jointed fingers.
  • Flat feet.
  • Enlarged testicles (in males, after puberty).
  • A high-arched palate (the roof of the mouth).
  • Low muscle tone.

Behavior:

  • Attention-deficit/hyperactivity disorder (ADHD).
  • Social anxiety, shyness.
  • Flapping or biting their hands.
  • Poor eye contact.
  • Sensory disorders – sensitivity to crowds, touch, sounds, foods and textures.
  • Difficulty picking up “social cues.”

Sometimes people with fragile X syndrome have other health conditions. In one survey, parents reported that their children also had:

  • Seizures (epilepsy).
  • Sleep problems. According to a different study, 4 in 10 people with FXS and autism spectrum disorder have sleeping problems. This is compared to 3 in 10 people who have only FXS.
  • Aggressiveness or irritability. People with FXS in addition to autism spectrum disorder are more likely to be aggressive.
  • Self-injury behaviors.
  • Obesity.

How long does fragile X syndrome last? Is fragile X syndrome curable?

Fragile X is a lifelong syndrome. It can’t be cured.

How is fragile X syndrome diagnosed? What tests are done?

Diagnosing fragile X syndrome requires DNA from blood, amniotic fluid or other tissues. Your healthcare provider will send the sample to a laboratory that will determine if your child has the FMR1 gene.

If you’re pregnant and concerned that your child has fragile X syndrome, you can see a genetic counselor where you may undergo the following prenatal tests:

  • Amniocentesis: The healthcare provider takes a sample of the amniotic fluid for testing.
  • Chorionic villus sampling: The healthcare provider takes a sample of cells from the placenta for testing.

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.

What questions might a healthcare provider ask to help diagnose fragile X syndrome?

Before your healthcare provider or genetic counselor orders a test for fragile X syndrome, they may ask you the following questions:

  • What symptoms have you noticed in your child?
  • How well does your child learn?
  • Is your child shy?
  • Does your child have sleep problems?
  • Is your child anxious?
  • Does your child avoid eye contact?
  • Do they have any abnormal physical features?
  • How is your child’s speech?

What are the treatments for fragile X syndrome? What medications are prescribed?

Fragile X syndrome can’t be cured, but the symptoms can be treated. Your child’s healthcare provider may prescribe a variety of medications, but therapy should also be included – therapy that works with coping and behavioral skills.

Examples of medications, categorized by symptom, include:

Seizures or mood instability:

  • Lithium carbonate.
  • Gabapentin (Neurontin®).

ADHD:

  • Methylphenidate (Ritalin®, Concerta®) and Dextroamphetamine (Adderall®, Dexedrine®).
  • Venlafaxine (Effexor®) and Nefazodone (Serzone®).

Aggression or obsessive-compulsive disorder:

  • Fluoxetine (Prozac®).
  • Sertraline (Zoloft®) and Citalopram (Celexa®).

Sleep issues:

  • Trazodone.

· Melatonin.

This is just a short list of possible medications your child’s healthcare provider may prescribe. Talk to the provider about possible side effects and complications that may come with each medication.

Can fragile X syndrome be prevented?

No, fragile X syndrome can’t be prevented.

What can I do to reduce my child’s risk of fragile X syndrome?

Unfortunately there isn’t anything you can do to reduce your child’s risk of fragile X syndrome. If you have the FMR1 gene, they could, too.

What’s the outlook for people with fragile X syndrome?

Some individuals with fragile X syndrome are able to live independently. Surveys show that around 4 in 10 women and 1 in 10 men with fragile X syndrome grow up to have a high level of independence. Women more than men have the following abilities:

  • Reading books that include new ideas and new words.
  • Speaking complex sentences.
  • Speaking at a normal speed.

Women with FXS thrive more than men. Women, specifically 8 out of 20 women, don’t need help with daily activities – neither do 1 in 20 men. Most women get a high school diploma but a majority of men don’t. Nearly half of women with FXS have full-time jobs but only 2 in 10 men.

Is fragile X syndrome permanent?

Yes. It’s a lifelong syndrome.

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. Your child’s teacher might be able to make environmental adjustments and curricular adjustments.

Environmental adjustments:

  • Keep the noise level down.
  • Have natural lighting.
  • Avoid crowds.

Curricular adjustments:

  • Have visual aids like diagrams, charts, color coding or pictures.
  • Help your child learn by using materials they find very interesting.
  • Have your child work in small groups.

Be sure to inform your child’s school that they have fragile X syndrome. Have a conversation with their teacher about their unique needs. You may also meet with a school psychologist and/or counselor. They work with children three years old and older. Other healthcare providers you may want to connect with are occupational therapists, behavior therapists and speech and language therapists. Talk with your local school and healthcare providers for referrals.

What’s it like to have fragile X syndrome? What’s everyday life like with fragile X syndrome?

It’s important to note that there are many positive characteristics of people with fragile X syndrome. For example, researchers have noted that they’re:

  • Helpful.
  • Kind.
  • Thoughtful.
  • Friendly.
  • Good imitators.
  • Good at visual and long-term memory.
  • Humorous.
  • Does fragile X syndrome get worse with age?
Dr Rohit Bhaskar, Physio
Dr Rohit Bhaskar, Physio Dr. Rohit Bhaskar, Physio is Founder of Bhaskar Health and Physiotherapy and is also a consulting physiotherapist. He completed his Graduation in Physiotherapy from Uttar Pradesh University of Medical Sciences. His clinical interests are in Chest Physiotherapy, stroke rehab, parkinson’s and head injury rehab. Bhaskar Health is dedicated to readers, doctors, physiotherapists, nurses, paramedics, pharmacists and other healthcare professionals. Bhaskar Health audience is the reason I feel so passionate about this project, so thanks for reading and sharing Bhaskar Health.

Post a Comment

Listen to this article

Subscribe

* indicates required