Fragile X Syndrome

About Fragile X

What is Fragile X Syndrome?

Fragile X Syndrome (FXS) is a genetic disorder caused by a mutation (a change in the DNA structure) in the X chromosome. It is the most common known cause of inherited developmental disability worldwide.  In addition to learning problems, FXS results in a range of emotional and behavioural problems including anxiety, ADHD, hyperarousal and autism. Physical features are found in some but not all individuals. Affected individuals can be mildly to severely affected.

How common is it?

One in 3,600 males and one in 5,000 females are affected. One in 250 females carry the premutation and will pass the gene on to 50% of their offspring, male or female, any of whom may be affected.  

What is the cause?

The mutation causing FXS is found in the fragile X messenger ribonucleotide 1 gene (FMR1).  
The gene expands, which disrupts its normal function and results in lowered production of FMR1 protein, needed for normal development. If the gene expands to between 55 and 200 repeats, this is termed ‘premutation’ or ‘carrier’. Expansions of more than 200 repeats are termed ‘full mutation’ and cause FXS.  

What are the clinical features?

Physical Features

Boys and girls may have prominent ears, high forehead, high palate, hyper-flexible joints, soft skin and flat feet. After puberty, the face may gradually become longer and boys may develop testicular enlargement. Medical complications do not generally develop, however, ear infections are common and there is an increased risk of epilepsy (seizures), strabismus (squint), mitral valve prolapse, hernia and joint dislocations. Typical physical features are often not present, especially in children and females.

Developmental Features

Intellectual disability occurs in 95% of males and 65% of females. Global problems tend to occur with learning disabilities and delays in speech, fine and gross motor movements and co-ordination difficulties.

Behavioural and Emotional Features

Common features include anxiety (hyperarousal), hyperarousal (extreme reaction) or aversion to sensory stimuli (loud noise, touch, strong smells or tastes, eye contact), attention deficit disorders with or without hyperactivity and difficulties with expressive language. Autism-like features include hand flapping and biting (or chewing on clothes), poor eye contact and resistance to changes in routine. A diagnosis of autism spectrum disorder, pervasive developmental delay may have been made. Whilst females may initially appear less affected, they often suffer with shyness, social anxiety, panic disorder, moodiness and a range of executive function disorders.

A note on carriers:

A sub-group of carriers of the premutation may exhibit mild features of the full mutation including learning or emotional difficulties. 

• There is a higher risk of early menopause in females (Fragile X-associated primary ovarian insufficiency (FXPOI))  

• Older males may develop a neurological disorder with hand tremour and balance problems (Fragile X-associated tremor/ataxia syndrome (FXTAS) 

Strengths & Weaknesses associated with Fragile X Syndrome

Strengths

• Learn visually eg pictures,computers
• Whole word, number and pattern recognition, ‘gestalt’ learning
• Long term and incidental memory
• Concrete, relevant tasks
• Strong imitation skills, drama
• Good functional life skills
• Friendly, good sense of humour

Weaknesses

• Short-term memory
• Auditory-only processing
• Abstract concepts
• Sequencing, praxis and planning
• Fine and gross motor
• Perceptual, visual motor
• Social, language, semantic-pragmatic
• Attention and initiation

Diagnosing Fragile X Syndrome

How is it diagnosed?

Any doctor can request a blood test (or cheek swab) for “DNA studies for fragile X syndrome”.  
“Microarray karyotyping”) should also be requested to exclude other genetic disorders. Testing should be done in combination with genetic and supportive counselling. 

Who should be tested?

Testing should be considered for: 

 Any male or female with intellectual disability, developmental delay, learning disabilities, or autism-like features; 

• Individuals who have only had a cytogenetic test previously, or who were tested prior to 1991; 

• Pre-conception: women or their partners with a personal or an extended family history as above, or who wish to be tested; 

• Individuals with a confirmed family history of fragile X syndrome who could have inherited the gene; 

• Obstetric: Pregnant women or their partners with a family history of fragile X syndrome, or intellectual disability of unknown cause; foetuses of a parent known to be a fragile X carrier; couples with a personal or family history of premature menopause; if undergoing IVF, CVS or amniocentesis. 

Early detection allows the implementation of effective treatment and intervention strategies thus optimising outcome. As this is an inherited condition, diagnosis also allows families to make informed choices regarding both treatment and family planning. 

Strategies & Treatments available

Treatments

• Speech and language therapy
• Occupational therapy with sensory integration
• Special education
• Psychological therapies
• Medical and pharmacological

Strategies

• Prepare for transitions with highly structured routines
• Maximise visual input (use pictures, timetables)
• Minimise auditory and visual distractions
• Utilise calming strategies and distractors
• Positively reinforce good behaviour