What is Fragile X Syndrome (FXS)?
Fragile X Syndrome is the most common known cause of inherited intellectual and developmental disability and the most common genetic cause of autism. It causes learning and behavioural challenges which range from mild to severe.
FXS occurs in both males and females. Whilst males generally appear more affected than females, the latter are often significantly affected.
What causes FXS?
FXS is caused by the expansion or lengthening of the FMR1 gene on the X-chromosome, known as a gene mutation. When the gene lengthens, it switches off production of a protein that is involved in brain development and other functions.
How is the Fragile X gene inherited?
The gene can be passed on to males or females and the Fragile X gene may be apssed down through each generation.
Females have two X chromosomes and males have one X and one Y.
Normally, the X chromosome contains between 6 and 50 repeats of the FMR1 gene). In some people, this gene may contain between 50 and 200 repeats, this is known as a premutation. A person with this gene premutation is called a ‘carrier’.
When this gene lengthens to over 200 repeats this is called a ‘full mutation’.
Daughters born to male carriers will inherit their father’s affected X chromosome and so they will always also be carriers. Sons born to male carriers will not inherit their fathers affected X chromosome and instead will inherit their fathers unaffected Y chromosome so they cannot inherit the gene from their fathers.
Because females have two X chromosomes, children of either gender born to women who carry the premutation gene have a 50% chance of inheriting the affected gene. If they inherit the affected gene, depending on how much the gene lengthens, they will either be a carrier or fully affected.
Watch the digital animation at the link below for more information about the genetics of Fragile X.
How many Australians are affected by FXS?
FXS appears in people from all ethnic, racial and socio-economic backgrounds. It’s estimated that approx 100,000 Australians may carry the gene. The vast majority of those will carry the premutation gene.
It is estimated that in Australia, 1 child per week is born who is fully affected and 20 are born carriers of Fragile X.
What are the implications of this for the rest of my family and other children?
If a family member is found to be affected by FXS, this means that other people in the extended family may also be affected. The Fragile X Association of Australia strongly recommends that all other family members at risk of carrying the gene are informed and tested. This is best done with the help of a genetic counsellor.
What is the impact of being a ‘Fragile X carrier’?
The term Fragile X premutation carrier, means that the person is carrying a shorter expansion of the Fragile X gene. A percentage of those people will have characteristics that are typical of Fragile X. They may have social, or communication issues, learning problems at school, anxiety and depression. Some people who are carriers may not appear affected at all.
Women who are carriers can experience Fragile X Premature Ovarian Insufficiency (FXPOI), which can lead to early menopause.
Men and women who are carriers can also develop Fragile X Associated Tremor Ataxia Syndrome (FXTAS). Men are more likely to develop FXTAS than women and it may develop after the age of 50. It can affect balance and memory, and cause tremors and other neurological problems. It is sometimes misdiagnosed as Parkinson’s type disease.
What are some of the signs of FXS?
The way FXS affects people will vary. Some of the signs of FXS are:
- Developmental features: intellectual disability, learning difficulties, developmental delay, speech and communication difficulties, coordination issues, problems with fine and gross motor skills
- Behavioral and emotional features: anxiety and shyness, attention deficit hyperactivity disorder (ADHD), autistic type behaviors, problems with eye contact, tactile defensiveness, repetitive speech, aggression.
- Physical features including: low muscle tone and loose joints, long narrow face, prominent ears, high palate, large testicles (in some post pubescent males), mitral valve prolapse (heart murmur)
What does this mean for the development from infancy to adulthood?
People with FXS have a normal life expectancy. They may develop very strong, functional life skills, such as the ability to operate equipment or a computer, undertake household tasks, learn to drive a car and work. Many will be able to live by themselves, although most people will require support.
How is FXS diagnosed?
FXS is diagnosed through a simple blood test.
The doctor will request a DNA test for FXS. Currently the test is covered by Medicare if the person exhibits features of Fragile X or if they’re related to someone with Fragile X.
Who should be tested for Fragile X?
The Association recommends the following groups of people should be tested for Fragile X:
- All people with intellectual disability or autism spectrum disorder
- Any person with significant learning difficulties, ADHD mild cognitive disability and anxiety
- People with a family history of Fragile X
- Women experiencing early menopause
- People experiencing Parkinson’s type diseases.
What are the implications of genetic testing?
Receiving a genetic diagnosis can be worrying. It can also be hard for family members to tell other family members they need to be tested. However a genetic diagnosis provides options for targeted treatment and support as well as a choice of family planning options. A genetic counsellor can help with contacting other family members.
How important is early diagnosis?
Early diagnosis gives families options. It allows for family planning and informing other family members who may carry the gene. It also allows for early intervention strategies to be put in place for the child and family as well as implementation of targeted treatment and management strategies for people of all ages.
What are their strengths of people with FXS?
People with FXS have very real strengths. They have a wonderful sense of humour, are caring, compassionate and helpful. Some people with FXS have good verbal and reasoning skills. They often have great memories and excellent imitative skills
After the initial diagnosis, what happens next?
After the diagnosis is made its important to provide the child or adult with the required intervention strategies. This may include a full developmental and clinical assessment.
What treatments are available for people affected by Fragile X?
There’s a wide range of treatment and management strategies for both children and adults affected by Fragile X. Anxiety, and attention deficit hyperactivity disorder may be treated with medications prescribed by your doctor. There’s also a very wide range of behavioural management strategies and educational strategies.
What do you mean by a multi-disciplinary approach – what does this involve?
A multi-disciplinary approach to treating FXS is very important and that’s because the development in FXS is very disordered, so children develop in speech and language, in their motor skills, in their self-help skills, how they do things for themselves, in their play skills, in their cognitive speaking and attention skills, all at a different rate and a different pace. For that reason, a number of different professionals need to be involved who specialise in particular developmental areas to assess and manage difficulties children and adults have. These may include, vision, hearing, medical conditions, speech and language, occupational therapy, psychology, education and work training. Each person will have their own individual needs that will require management by some or all of the above at different stages in their lives.
Ideally how often should a person with FXS attend therapy with these specialists?
The therapists are involved generally as consultants to the FXS person and the family. The frequency of therapy will depend on your therapist’s advice which is based on your family member’s needs.
What medical treatments are available for children or adults diagnosed with Fragile X?
Medical professionals will advise you on management and treatment options. This will include taking a relevant history, conducting an examination, arranging further tests and assessments, providing information on behaviour management and medication options and referral to other professionals if needed. Medications can be very helpful for management of common behavioural and emotional conditions seen in FXS such as anxiety, ADHD, obsessive compulsive behaviour and mood instability.
Relationship between Autism and FXS
Whereas autism is a behavioral diagnosis, FXS is a medical or more accurately, a genetic diagnosis. When associated with FXS, the autism is caused by the genetic change or mutation in the Fragile X gene. If a child is diagnosed with autism and then diagnosed with FXS, he or she still has autism, it is just that the cause of their autism is known.
How many people with FXS also have Autism?
Many studies have evaluated the Fragile X-autism link over the past decade. These studies have shown the percentage of children with Fragile X who have autism varying from 5 to 33 percent. This range may be due to the fact that the diagnostic criteria for autism have varied and the diagnostic tools used have changed.
Since many people with Fragile X are interested in social interactions, they may not meet the diagnostic criteria for autism, even as they exhibit some feature. Autism is more common in males with FXS than in females.
How many people with autism have FXS?
It is recommended that everyone with autism, both male and female, be referred for genetic evaluation and testing for Fragile X. For more information on Autism and FXS see the National Fragile X Foundation site.