Overview

Do you know that Fragile X Syndrome (FXS) is known as the most common inherited intellectual disability and autism spectrum disorder, affecting both persons assigned male at birth (AMAB) and those assigned female at birth (AFAB)?¹ Research shows that about 1 in 7000 males and 1 in 11,000 females are diagnosed with Fragile X syndrome. 

This article will explore what FXS is, its unique features and its cognitive impact. A deeper understanding of the cognitive impact of FXS will help provide the needed support and interventions for those diagnosed with the condition.

Understanding Fragile X Syndrome

FXS is a genetic disorder previously known as Martin Bell syndrome. It is caused by an abnormality in the Fragile X Messenger Ribonucleoprotein 1 gene (FMR1 gene).² The FMR1 gene is located on the X chromosome and produces a protein called FMRP (Fragile X Mental Retardation Protein) which helps in proper cell functioning. 

The mutation in the FMR1 gene leads to the expansion of the CGG (cytosine-guanine-guanine) trinucleotide located in the 5’ untranslated region of the X-linked FMR1 gene. Most people have less than 45 CGG repeats. But in those with FXS, the number of repeats expands to over 200, which is called a full mutation. People with 55 to 200 repeats are known as premutation carriers.³

When the CGG repeats increase, the FMR1 gene becomes “silenced,” meaning it stops making enough FMRP. Without this protein, brain cells cannot communicate as they should. This leads to problems with learning, behaviour, and development, which are common in people with Fragile X Syndrome.

Cognitive impact of Fragile X syndrome

Individuals with FXS exhibit some level of intellectual disability, which ranges from mild to severe, and it affects a child’s intellectual, physical, mental, and behavioural growth and development. The cognitive impacts of FXS include:

Learning difficulties

Children with FXS often struggle with attention, working memory, and processing speed. These difficulties can significantly impact their academic performance if proper measures are not put in place. 

Due to the learning difficulty and individual needs of children with FXS, it is encouraged that parents, teachers, school psychologists, and caregivers should understand the specific learning styles of their wards or children. They can opt for individualised education plans (IEPs), use of visual signs, provision of a supportive learning environment, and allow the child to express themselves freely.⁴

Speech/language delay

Children with FXS tend to have a speech delay when compared to their peers. They don’t usually speak until they’re about 2 and a half years old. Language development for individuals affected with FXS can be receptive (what is understood), expressive (how a person uses language for expression), and pragmatic (how communication is expressed in a social context). 

Children with FXS have faster and stronger receptive skills than their expressive language skills. They find it easier to understand than to express themselves verbally. For expressive language, they struggle to find the right words to express their wants and needs. When compared with children of the same cognitive development level, children with FXS are found to have a slower language expression level.⁵ 

Pragmatically, they find it hard to initiate conversations. They become anxious and avoid making eye contact with people. It’s also difficult for them to interpret body language, gestures, and facial expressions, leading to misunderstandings and awkward social interactions.

Attention deficit/hyperactivity disorder (ADHD)

ADHD is a neurodevelopmental disorder that is associated with FXS.⁶ Symptoms of ADHD in children affected with FXS include difficulty in staying focused, being easily distracted, hyperactivity, and impulsivity. The hyperactivity and impulsivity of these children could manifest as an inability to stay in a place for too long, fidgeting, or interrupting the discussions of others.

Social anxiety 

Social interactions can be quite challenging for individuals with FXS.⁷ They are shy, avoid social interactions, fear being embarrassed, and find it difficult to make eye contact. Their avoidant behaviours make it difficult for them to form and maintain relationships with others, leading to feelings of isolation, low self-esteem, and inadequacy.

Executive function

Individuals with FXS struggle with strategic planning and management skills. This difficulty can affect academic performance and the ability to manage daily activities like dressing, preparing a meal, or managing tasks.⁸ They may also have difficulty with thinking flexibly and generating multiple solutions to problems, leading to feelings of frustration and anxiety. 

Additionally, individuals with FXS often have a deficit in working memory (the ability to store information in the mind for a long time) and cognitive flexibility (the ability to switch or adapt to new situations/tasks).⁸

Diagnosis of FXS

Identifying and diagnosing FXS enables early intervention that can improve cognitive, behavioural, and social development and also reduce the severity of the symptoms. On average, male children with FXS are diagnosed between 35 and 37 months of age, while female children are typically diagnosed around 42 months.⁹ The diagnosis is done by drawing blood samples from affected children. Then, the healthcare providers will send blood samples to a laboratory to detect if a child has the FMR1 gene.

A prenatal test could also be done while the foetus is still in the birth parent’s womb. This helps to detect the mutated gene in the fetus. You may undergo these prenatal tests including:

• Amniocentesis: Your healthcare provider takes a sample of amniotic fluid to test for the FMR1 genetic mutation
• Chorionic villus sampling: A sample of cells from the placenta is taken to test for the mutation

If you’re concerned your fetus might be affected by this syndrome and want to test during pregnancy, there's a need to seek the counsel of your healthcare provider.

Intervention strategies

After the diagnosis has been confirmed, early interventions can be put in place. While there is currently no cure for FXS, various therapeutic strategies have proven effective in managing symptoms and enhancing quality of life. These strategies may include:

Speech and language therapy 

This can help improve communication skills and develop language comprehension. It also helps individuals improve their abilities to express themselves, understand others, and engage in meaningful social interactions.

Individualised education plans (IEPs) and specialised instructional strategies can help a child with FXS succeed in school. Parents, teachers, and therapists should collaborate for the effectiveness of this plan.

Medications

A pharmacotherapeutic approach is now adopted in the treatment of FXS to reverse the neurobiological abnormalities.¹⁰

Family support and training 

Families need a strong support system for constant advice, techniques, guidance, and a sense of community. This is why organisations such as the Fragile X Foundation offer resources and support to families of individuals with FXS.

Occupational therapy

Occupational therapy aims to enhance fine motor skills and improve the sensory processing of individuals affected with FXS. Occupational therapists adopt the use of play-based therapy and activities that promote hand-eye coordination to enable individuals to carry out their daily tasks and activities.

FAQs

Does Fragile X Syndrome lead to mental retardation?

Fragile X syndrome is known as the lead cause of intellectual disability (historically termed “mental retardation”). However, the nature and extent of cognitive impairment varies among affected individuals.

What are the symptoms of Fragile X Syndrome?

The physical symptoms of Fragile X syndrome include a large head, flexible joints, hypotonia, shyness/poor eye contact, obsessive compulsive disorder, sensory disorders, problems with math, a narrow face, etc. 

How is Fragile X Syndrome treated?

There is no cure yet for Fragile X syndrome. However, certain medicines can be taken to minimise the symptoms. Early intervention is also important, so you should seek the help of a professional therapist if you notice a delay in your child’s development.

Is Fragile X Syndrome a genetic or chromosomal disorder?

Fragile X syndrome is an inherited genetic disorder that occurs as a result of the mutations in the Fragile X Mental Retardation 1 (FMR1) gene on the X chromosomes.

Can people with Fragile X Syndrome live a normal life?

Sure, they can because none of the symptoms are life-threatening. While some people may need the assistance of loved ones like family and friends, others can also live independently. 

Summary

Understanding the cognitive impact of Fragile X Syndrome is essential to providing essential support and interventions that enhance the quality of lives of those affected by it. The impacts include learning difficulties, attention-deficit/hyperactivity disorder, social anxiety, executive function, and speech/language delay. With early diagnosis and tailored approaches like individualised education plans, occupational therapy, medications, and family support, some of the challenges of FXS can be addressed. 

Research is still ongoing to provide additional strategies and interventions to better help individuals with FXS achieve their full potential. If you know someone diagnosed with FXS, it's advisable to seek advice from professional therapists or healthcare providers on the best way to manage the condition.