Introduction

Fragile X Syndrome is the most common, inherited form of intellectual disability and the most common identifiable genetic cause of autism. ¹ The condition is the result of a genetic alteration on the FMR1 gene causing a change in the production of a specific protein in the developing foetus. Fragile X syndrome affects both males and females and can be passed on to children either maternally or paternally by individuals said to be premutation carriers, or by individuals with a full mutation.

An estimated one in 3,600 males and one in 4,000 – 6,000 females ² have the full mutation of Fragile X which can lead to global developmental delay and a wide range of learning difficulties, behavioural challenges and physical problems. It is thought that approximately one in 700 males and one in 260 females have the Fragile X premutation ³ and therefore have a chance of having a child with either the pre or full mutation type of the condition. Fragile X syndrome is found in all populations, ethnicities and socio-economic groups.⁴

Cause and diagnosis of Fragile X Syndrome

Fragile X Syndrome was named as such due to the observed flaky, unstable appearance of the affected x chromosome in those with the condition. The alteration consists of an expansion of a single gene sequence on the X chromosome and diagnosis is determined according to the size of the expansion or number of repeats on the sequence. Those without Fragile X have between 6 and 40 repeats, between 55 and 200 repeats is classed as premutation and 200+ repeats indicates a full mutation resulting in Fragile X Syndrome and its associated difficulties. Between 40 and 55 repeats is considered to be a ‘grey area’ where normal and premutation overlap.  ⁵

Diagnosis is made through analysis of a blood sample and should be accompanied by comprehensive genetic counselling so that the consequences for other family members and future generations can be explained. Diagnosis is considered to be of utmost importance for both individuals with the syndrome as well as families so that appropriate support and intervention can be introduced and an assessment of genetic implications can be made. ⁶  A confirmed diagnosis can also reduce the psychological distress which can arise as a result of uncertainty or inaccurate diagnosis and therefore help families to focus on the future.

Symptoms and characteristics of Fragile X Syndrome

The typical physical characteristics of individuals with Fragile X syndrome result from the disruption of messages instructing cell formation during foetal development, however, these physical aspects are also commonly found within the general population and occasionally may not be present in the Fragile X individual at all.

Physical characteristics include:

• Long, largish head and jaw
• Protruding ears
• Loose joints and ligaments
• Flattened nasal bridge
• High arched palate
• Single palmar/plantar crease
• Postpubertal testicular enlargement
• Cardiovascular complications ⁷

Intellectual and behavioural characteristics include:

• Mild to severe intellectual disability
• Speech, language and communication difficulties
• Shyness and social anxiety
• Aggression and self-injurious behaviours
• Autistic traits
• Hyperactivity and attention/impulse control

For many children with Fragile X early development may seem to be normal, however for others, global delay presenting as late physical (sitting, crawling, walking) and communicative (smiling, pointing, talking) developmental milestones can occur. Problems with feeding, sleeping and toileting may also be seen and frequent ear infections are often common.  ⁸

Speech and language difficulties are almost always present in those with Fragile X syndrome and often an early clue to diagnosis. ⁹ Individuals often have cluttered speech, echolalia (repeating what has been heard), perseveration (getting stuck on a phrase or topic) and unusual intonation. More positively, individuals can have a vocabulary within the normal range and although expressive speech is commonly affected, language comprehension is relatively good. ¹⁰ In spite of the many difficulties associated with the condition, people with Fragile X Syndrome can often be pleasant and sociable with a well-developed sense of humour. ¹¹

All males with a full mutation will be affected by symptoms however, as females have two x chromosomes, those with a full mutation are less likely to experience these difficulties to the same extent due to the influence of the unaffected x chromosome. Cognitive ability and behavioural traits amongst females with a full mutation can vary greatly but the same level of understanding and support is needed for girls with Fragile X and their families and carers. ¹²

Effects of Fragile X on premutation carriers

Although individuals carrying the premutation version of Fragile X were previously believed to exhibit no symptoms, a link has now been made between carriers and various physical and intellectual problems.

Male premutation carriers are at risk of Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), a neurodegenerative condition more commonly affecting males in later life. Symptoms include tremors, balance problems and cognitive decline such as memory loss, difficulty in planning or decision-making and mood changes. FXTAS is found in around 30-40% of male premutation carriers and approximately 8-16% of female carriers over the age of 50 years. ¹³

Female premutation carriers are also at risk of early menopause or Fragile X-associated Primary Ovarian Insufficiency (FXPOI) and it is believed that all females with the premutation have decreased ovarian function. ¹⁴ Approximately 20-25% of premutation carriers will experience early menopause, on average five years earlier than the general population although in extreme cases menopause can occur in the early 20’s. ¹⁵ Female premutation carriers can also experience difficulties with numeracy and vocabulary as well as being more likely to suffer from shyness, social anxiety and depression. ¹⁶

Support for individuals and families

Although there is no cure for Fragile X Syndrome, many treatments exist in order to help people fulfil their potential and to improve quality of life for both individuals and families living with the condition. Early interventions should be based on the identification of an individual’s physical, intellectual and behavioural needs and ongoing assessment can ensure the most beneficial therapies. ¹⁷

Educational considerations should include limiting class or group size to increase individual tuition time, being aware of noise and lighting levels to reduce distraction and providing a predictable, consistent learning environment. Problems with attention and concentration can be helped by short periods of focused learning followed by breaks and frequent rewards for concentration. It is essential that schools and teachers understand the wide range of abilities amongst individuals with Fragile X Syndrome and the performance discrepancies in different areas such as conversation, numeracy or visuo-spatial skills. It is also important that any resistance to or poor performance in certain tasks is not simply attributed to laziness or stubbornness, but understood, assessed and treated appropriately. ¹⁷

Speech and language therapy is essential, particularly for boys with Fragile X syndrome and is most beneficial with input from both school and family, and communication can be augmented by the use of sign language or alternative picture-based systems. Occupational therapy and physiotherapy are also worthwhile for addressing physical difficulties such as problems with fine and gross motor delays, joint hypermobility and low muscle tone. In some instances where such problems as hyperactivity, aggression or mood disorders become unmanageable, medication can play a role in effective treatment. ¹⁷

Although the difficulties associated with Fragile X Syndrome are numerous and varied, the condition has no specific health problems which affect lifespan or wellbeing in adult life. As such it is essential to make accurate ongoing assessment of needs and to use this information to plan and support appropriately in order to promote the best possible outcome for each individual and those who care for them. ¹⁸

References

1 The National Fragile X Foundation, 2011, Summary of Fragile X Syndrome [online], Available at: http://www.fragilex.org/html/summary.htm [Accessed 10 October 2011].

2 The National Fragile X Foundation, 2011, Summary of Fragile X Syndrome [online] Available at: http://www.fragilex.org/html/summary.htm [Accessed 10 October 2011].

3 The National Fragile X Foundation, 2011, Prevalence of Fragile X Syndrome [online] Available at: http://www.fragilex.org/html/prevalence.htm [Accessed 10 October 2011].

4 The Fragile X Association of Australia, 2011, About Fragile X [online] Available at: http://www.fragilex.org.au/fragilex/about-fragile-x [Accessed 10 October 2011].

5 The National Fragile X Foundation, 2011, The Fragile X DNA Test [online] Available at: http://www.fragilex.org/html/dnatest.htm [Accessed 10 October 2011].

6 Turk, J., 2004. The importance of Diagnosis. In: D. Dew-Hughes, ed. 2004. Educating Children with Fragile X Syndrome, Abingdon, Routledge, pp15-20. Ch2.

7 The Fragile X Association of Australia, 2011, Appearance [online] Available at: http://www.fragilex.org.au/fragilex/appearance [Accessed 10 October 2011].

8 The Fragile X Association of Australia, 2011, Behaviour [online] Available at: http://www.fragilex.org.au/fragilex/behaviour [Accessed 10 October 2011].

9 The National Fragile X Foundation, 2011, Speech and Language Therapy [online] Available at: http://www.fragilex.org/html/speech1.htm [Accessed 10 October 2011].

10 The Fragile X Association of Australia, 2011, Speech [online] Available at: http://www.fragilex.org.au/fragilex/speech [Accessed 10 October 2011].

11 The Fragile X Association of Australia, 2011, Behaviour [online] Available at: http://www.fragilex.org.au/fragilex/behaviour [Accessed 10 October 2011].

12 The National Fragile X Foundation, 2011, How does the Premutation differ from the Full Mutation [online] Available at: http://www.nfxf.org/html/premutation.htm [Accessed 10 October 2011].

13 The National Fragile X Foundation, 2011, Fragile X-Associated Tremor/Ataxia Syndrome(FXTAS) [online] Available at: http://www.fxtas.org/index.htm [Accessed 10 October 2011].

14 The National Fragile X Foundation, 2011, Facts about Primary Ovarian Insufficiency (POI) [online] Available at: http://www.fragilex.org/html/menopause [Accessed 10 October 2011].

15 The Fragile X Association of Australia, 2011, Carriers [online], Available at: http://www.fragilex.org.au/fragilex/carriers [Accessed 10 October 2011].

16 The Fragile X Society, 2010, Carriers of Fragile X [online] Available at: http://fragilex.org.uk/CarriersCorner.aspx [Accessed 10 October 2011].

17 Turk, J., 2004. Support for Individuals with Fragile X Syndrome and Their Families . In: D. Dew-Hughes, ed. 2004. Educating Children with Fragile X Syndrome, Abingdon, Routledge, pp181-188. Ch24.

18 O’Brien, G., 2004. Adults with Fragile X Syndrome. In: D. Dew-Hughes, ed. 2004. Educating Children with Fragile X Syndrome, Abingdon, Routledge, pp163-172. Ch21.

This information is not meant to replace the advice of any physician or qualified health professional. The information provided by Cerebra is for information purposes only and is not a substitute for medical advice or treatment for any medical condition. You should promptly seek professional medical assistance if you have concerns regarding any health issue.