Fragile X Syndrome (FXS): Meaning, Causes, Symptoms, Treatment

Written by Medicover Team and Medically Reviewed by Dr Shrikant Deshmukh , Neurologist

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Fragile X Syndrome (FXS) is a genetic disorder that affects brain development and causes various intellectual, behavioural and physical problems. It is the most common inherited cause of intellectual disability and a leading known genetic cause of autism spectrum disorders.

Fragile X occurs due to a mutation in the FMR1 gene on the X chromosome. This gene normally produces a protein essential for brain development but in FXS, the mutation prevents the gene from functioning properly.

The condition affects both males and females, though symptoms are usually more severe in males. Early recognition, supportive care and therapies can greatly improve the condition and quality of life.

Fragile X Syndrome Symptoms

The symptoms of Fragile X vary widely and some children may show clear signs early in infancy, while others are diagnosed later when developmental and learning challenges become more obvious. The severity of symptoms can differ between boys and girls.

• Delayed development: Slower achievement of milestones such as walking, speaking or toilet training.
• Learning problems: Difficulty with problem-solving, abstract thinking and academic performance.
• Emotional symptoms: Anxiety, frequent mood swings, irritability and sensitivity to stress.
• Repetitive behaviours: Hand-flapping, biting, rocking or other self-stimulatory movements.
• Attention difficulties: Problem in focusing, impulsivity and restlessness in classroom settings.
• Social challenges: Difficulty making eye contact, reluctance to engage with others and problems building friendships.

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Fragile X Syndrome Causes and Risk Factors

Fragile X Syndrome is caused by a genetic change in the FMR1 gene located on the X chromosome. This gene normally produces a protein (FMRP) that is essential for brain development and learning.

• CGG repeat expansion: A small DNA sequence in the FMR1 gene is repeated too many times. This excessive repetition switches off the gene and prevents it from making the necessary protein.
• Loss of fragile X protein (FMRP): Without this protein, the brain cannot develop and function normally, which causes intellectual disability, behavioural challenges and physical features of Fragile X.

• Family history: If parents or blood relatives are affected by Fragile X or related conditions, the risk is higher.
• Premutation carriers: Women carrying premutations of the gene may not have symptoms but can pass the full mutation to their children.
• Gender: Boys are more severely affected than girls, since they have only one X chromosome and no backup copy of the gene.

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Fragile X Syndrome Mutation Type and Inheritance

The mutation in Fragile X involves a section of DNA in the FMR1 gene that contains a CGG triplet repeat. The number of repeats determines whether a person is unaffected, a carrier or has the full syndrome.

Mutation Types:

• Normal range: 5 to 44 CGG repeats; here, the gene functions normally.
• Intermediate or Grey Zone: 45 to 54 repeats. It is not linked with Fragile X but may expand in future generations.
• Premutation: 55 to 200 repeats. It does not cause Fragile X symptoms directly but carriers can pass on an expanded form to children.
• Full Mutation: More than 200 repeats. This shuts down the FMR1 gene and stops the production of FMRP protein, which causes Fragile X Syndrome.

Inheritance Pattern:

The inheritance pattern of Fragile X explains why it is more common and more severe in males but can still affect females in varying degrees. Fragile X follows an X-linked dominant inheritance:

• Males: With only one X chromosome, a mutation causes more severe symptoms.
• Females: Having two X chromosomes, females may experience milder symptoms or sometimes no symptoms at all because the unaffected X chromosome can partially compensate.

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Fragile X Syndrome Features

Fragile X Syndrome presents many physical, developmental and behavioural features. These characteristics can be found more in boys than in girls because of the difference in their X chromosomes. Key features of Fragile X are as follows:

• Developmental features: Children show delays in sitting, crawling, walking and talking compared to their peers.
• Intellectual features: Learning difficulties are common and may range from mild problems in academics to more severe intellectual disability.
• Behavioural features: Many children display hyperactivity, attention problems, anxiety and behaviours similar to autism spectrum disorder such as poor social interaction.
• Physical features: Distinctive traits such as a long, narrow face, large ears, flexible joints and flat feet are seen, though it is not always present in all cases.
• Speech and language features: Expressive language develops slowly, and children may repeat words or phrases (echolalia).
• Social features: Many children struggle with maintaining eye contact, show extreme shyness or face challenges in forming relationships.

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What are the Complications or Side Effects of Fragile X Syndrome?

Fragile X Syndrome not only affects learning and behaviour but can also cause several long-term complications if not treated effectively. The following are some common side effects:

• Autism spectrum disorder (ASD): Many children with Fragile X show features of autism like poor eye contact, social withdrawal and repetitive behaviours.
• Seizures: Around 10 to 20% of children may experience seizures, which require medical management.
• Speech and learning delays: Difficulties with communication and academics can impact school performance and independence.
• Behavioural and social challenges: Aggression, hyperactivity and self-stimulatory behaviours may interfere with making friends or adjusting in social settings.
• Emotional health issues: Anxiety, depression and mood instability develop during adolescence and adulthood without proper support.
• Physical complications: Joint hyperflexibility, flat feet, scoliosis and other skeletal issues may appear as children grow.

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When to See a Doctor

You should see a doctor if your child has:

• Delayed milestones like late walking, talking or toilet training compared to peers
• Speech and language difficulties like slow speech development, repetitive words or unclear communication
• Learning challenges or problems understanding instructions and performing in school.
• Behavioural issues like hyperactivity, aggression, anxiety or repetitive movements.
• Social difficulties such as avoiding eye contact, extreme shyness or issues in making friendships.
• Seizures or frequent mood swings that disrupt daily life.
• Family history of Fragile X Syndrome.

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Diagnosis of Fragile X Syndrome

Fragile X Syndrome is suspected when a child shows developmental delays, learning problems or unusual behavioural traits. Because many of its symptoms can overlap with other conditions like autism or ADHD, doctors depend on specialised tests to confirm the diagnosis.

• Clinical evaluation: A pediatrician or genetic specialist first reviews the child's growth history, development and behavioural patterns. Physical features such as a long face, large ears or flexible joints may also provide early clues.
• Family history: Since Fragile X is inherited, doctors ask about relatives with intellectual disability, autism or learning difficulties.
• Genetic testing:
• DNA test (CGG repeat analysis): This is the most reliable way to diagnose Fragile X. It measures the number of CGG repeats in the FMR1 gene to determine whether the gene is normal, premutated or fully mutated.
• Chromosomal microarray (CMA): This may be used to find out other genetic conditions that cause developmental delays.
• Prenatal and carrier testing: If there is a family history, mothers may be offered genetic counselling and prenatal testing to check if they carry the Fragile X mutation.
• Additional assessments: Once diagnosed, doctors may recommend hearing tests, speech and language evaluations, behavioural assessments and psychological testing to know the child's strengths and needs.

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Effective Management and Treatment of Fragile X Syndrome

Treatment of Fragile X usually involves a multidisciplinary approach with doctors, therapists, teachers and families working together. Here are some effective ways to cure this syndrome:

1. Therapies

Therapies are the basics of Fragile X management and should begin as early as possible.

• Speech and language therapy helps children improve communication, reduce frustration and build stronger social skills.
• Occupational therapy assists with fine motor skills, hand-eye coordination and daily living activities like dressing, eating and writing.
• Behavioural therapy is useful for addressing aggression, hyperactivity, anxiety and repetitive behaviours. It teaches coping strategies and positive reinforcement methods.
• Physical therapy supports children with low muscle tone, joint problems or poor coordination in building strength and mobility.

2. Educational Support

Most children with Fragile X require a special education plan or learning strategies.

• Personalised Education Plans ensure lessons are adapted to the child's abilities.
• Smaller class settings, visual aids and step-by-step instructions can improve focus and learning outcomes.
• Social skills training helps children adapt better in school environments.

3. Medical Treatments

Doctors may prescribe medicines to manage specific symptoms:

• Stimulants for hyperactivity and attention problems.
• Anti-anxiety or antidepressant medications for mood swings and emotional difficulties.
• Anticonvulsants if seizures are present.
• Sleep aids for children who struggle with insomnia or poor-quality sleep.

Note: All medicines should be carefully monitored by a doctor, as each child responds differently.

4. Lifestyle and Family Support

• Structured routines can help reduce anxiety and behavioural outbursts.
• Friendly environments like reducing noise, bright lights or crowded settings can help children who are easily overstimulated.
• Parental support and counselling can ease the journey for the children.

5. Research and Emerging Treatments

Ongoing studies are exploring new therapies that target the brain changes in Fragile X. These are not yet widely available but they offer hope for more effective treatments in the future.

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Conclusion

Fragile X Syndrome is a genetic condition that affects learning, behaviour and development. It cannot be cured but timely diagnosis, therapies, educational support and medical care can help children and adults with Fragile X achieve their fullest potential. Families can manage challenges and improve their children's lives with the right guidance.

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