Clinical

Syndromes: Fragile X syndrome

Series about conditions with common symptoms that constitute syndromes


Long, narrow facial features and large ears and jawbone are associated
with Fragile X syndrome. Picture: Science Photo Library

Fragile X syndrome (FXS) is a sex-linked chromosomal abnormality, significantly associated with learning and intellectual disabilities. It is the most common inherited cause of learning/intellectual disabilities in the world.

Figures vary about the overall prevalence of FXS, but Hunter et al (2014) identified that 1 in 7,000 boys are affected while the ratio for girls is 1 in 11,000.

Although the long, narrow facial features and large ears and jawbone associated with FXS can be evident in the individual, these features are generally not present at birth and many people with FXS do not present with these facial features at all, which can prolong diagnosis.

Common characteristic

The most common characteristic of FXS is the presence of learning or intellectual disability. This can vary from mild learning difficulties with numeracy and literacy, to severe intellectual disabilities.

An important defining feature of FXS is speech and language delay. People with FXS relate well to other people, however, their anxiety in unpredictable situations can cause them to behave inappropriately and avoid social contact with others.

Other typical features include autistic-type features such as hand flapping or hand biting, social anxiety, avoidance of eye contact, difficulty in adapting to change in everyday routines. As the child ages, there can be a co-occurrence of other conditions such as attention problems, hyperactivity, aggression and self-injury.

FXS occurs where there are large alterations of the FMR1 gene, which is located on the X chromosome of the sex chromosomes (Raspa et al 2017). Everyone has one pair of sex chromosomes; females have two X chromosomes and males have one X chromosome and one Y chromosome. Women can carry the mutated FMR1 gene on an X chromosome, but will not necessarily present with the syndrome because the other X chromosome may compensate for the mutation.

Genetic testing critical

They are, however, at increased risk of passing on the mutated gene to the next generation, most commonly in males. Males have only one X chromosome and cannot compensate for the mutated FMR1 gene on the X chromosome. Genetic testing is critical for families who have a person with FXS.

Diagnosis of FXS is important for the affected children but also for other members of the family who may be carriers of the FMR1 mutated gene and their future generations (Hersh and Saul 2011). FXS is diagnosed with a DNA blood test which identifies full mutations of the FMR1 gene and pre-mutations of the FMR1 gene.

Identification of pre-mutations of the FMR1 gene is important as these individuals may not have the syndrome, but being carriers of the mutated gene they are at increased risk of passing on the mutated gene.

Health supervision is critical as the person ages as there are a range of health needs that are associated with FXS, such as the onset of seizures, mitral valve prolapse and premature menopause in females (Hersh and Saul 2011). The family of the individual with FXS will need support in adjusting to the diagnosis of their child and coping with the effects of this on the rest of the family.

Case study

Seán, not his real name, was an affectionate and active toddler whose physical and motor development appeared normal until he was about 15 months old when he started withdrawing from social situations, became anxious about routine change and lagged behind in speech and language development. Eventually, he became so distressed when out shopping or visiting friends his parents stopped taking him.

The family GP referred him to a psychologist and a speech and language therapist for support he was diagnosed with ‘global developmental delay’ when he was two.

His mother heard about Fragile X syndrome (FXS) through a local mother and toddler group. She requested a DNA blood test and the results proved positive. Seán was then diagnosed with FXS and the family were screened for the mutated gene, which helped to identify the likelihood of future generations being affected.

References

  • Hersh J, Saul R (2011) Health supervision for children with Fragile X syndrome. Pediatrics. 127, 5, 994-1006.
  • Hunter J, Rivero-Arias O, Angelov A et al (2014) Epidemiology of Fragile X syndrome: a systematic review and meta-analysis. American Journal of Medical Genetics. 164a, 7, 1648-1658.
  • Raspa M, Wheeler A, Riley C (2017) Public Health Literature Review of Fragile X syndrome.

Sinéad Foran is programme leader and lecturer in intellectual disability nursing at Waterford Institute of Technology, Waterford, Ireland

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