Fragile X syndrome

Fragile X syndrome is a genetic disorder caused by a change to one of the genes on the X chromosome. It is the most common inherited cause of intellectual disability, and it is also linked to features of autism spectrum disorder.

Fragile X syndrome affects around 1 in 3,600 boys and between 1 in 4,000 and 6,000 girls. It can cause a wide range of physical, developmental, behavioral and emotional difficulties, although the level of severity varies enormously from person to person.

Effects of Fragile X syndrome#

There is no single typical presentation. Some boys with Fragile X syndrome have a long, narrow face, a prominent forehead and large testicles. The most significant effects can include:

• Global developmental delay, including speech, language and communication difficulties
• Intellectual disability and learning problems
• Anxiety
• Attention deficit hyperactivity disorder (ADHD)
• Poor eye contact
• Autism-like behaviors, such as hand flapping and repeating words or sentences
• Difficulty with social interactions
• Difficulty processing sensory information

The severity of these effects varies considerably, and not every person with Fragile X syndrome will have every one of these characteristics.

Cause of Fragile X syndrome#

Fragile X syndrome is caused by a change to a gene on the X chromosome called FMR1. This gene normally produces a protein that helps the brain to function normally. If the gene is changed or altered, it cannot produce its normal protein, which can result in Fragile X syndrome.

The condition is inherited in a way known as ‘X-linked’, because the changed gene is on the X chromosome. This means that men with Fragile X syndrome are often more severely affected than women. Men have only one X chromosome, whereas women have two, only one of which carries the change.

Carriers of the Fragile X gene#

Although Fragile X syndrome itself is not common, the number of men and women who carry the changed FMR1 gene is significantly higher. It is estimated that around 1 in 150 women and 1 in 800 men are carriers. These people are known as ‘Fragile X pre-mutation carriers’.

Pre-mutation carriers may not have any symptoms of Fragile X syndrome, but they are at risk of passing on the changed gene and having a child or grandchild with the condition.

Pre-mutation carriers may also be at risk of developing health problems later in life. These are known collectively as Fragile X-associated Disorders:

• Around 20 per cent of female pre-mutation carriers experience reduced fertility or early menopause. This is called Fragile X-associated Primary Ovarian Insufficiency, or FXPOI.
• Older male and female pre-mutation carriers are at risk of a neurological condition called Fragile X-associated Tremor Ataxia Syndrome, or FXTAS. Problems with balance and gait, tremors and gradual intellectual decline are common in FXTAS.

Testing and diagnosis#

Fragile X syndrome and Fragile X-associated disorders can only be diagnosed by DNA testing – usually a blood test, but sometimes via cheek swab or mouthwash. Where possible, testing should be done at a recognized genetics service.

If there is a diagnosis of Fragile X syndrome, it is important that immediate and extended family members are also tested to identify others who may carry the changed gene. This is called cascade testing.

DNA testing is recommended for:

• People with intellectual disability, developmental delay or learning disability together with features of Fragile X syndrome, such as anxiety, ADHD or characteristics of autism spectrum disorder
• People with a family history of Fragile X syndrome or intellectual disability
• Men or women over 50 with balance or gait problems, tremor or dementia
• Any woman with problems with fertility or early menopause (under 40), or who is considering testing before or during pregnancy

Diagnosis is often delayed, and it is not uncommon for families to have a second child born with Fragile X syndrome before the first child has been diagnosed. A prompt diagnosis is important so that families can access appropriate early intervention services to help their child reach their full potential.

Genetic counseling#

The facts about Fragile X syndrome are complicated, and the implications for families can be serious. It is recommended that parents and family members ask their doctor to refer them to a genetics service, both for testing and for follow-up counseling.

Genetic counselors are health professionals qualified in both counseling and genetics. As well as providing emotional support, they can help you understand Fragile X syndrome and what causes it, how it is inherited, and what a diagnosis means for your child’s health and development and for your family. They are trained to provide information and support that is sensitive to your family circumstances, culture and beliefs, and they can also explain the range of reproductive options that are now available.

Key points#

• Fragile X syndrome is a genetic disorder caused by a change to a gene on the X chromosome.
• It is the most common inherited cause of intellectual disability.
• It can cause a range of physical, developmental, behavioral and emotional difficulties.
• Men are often more severely affected than women, because men have only one X chromosome while women have two, only one of which carries the change.
• Pre-mutation carriers may have no symptoms but can pass on the gene and may be at risk of health problems later in life.

Where to get help#