Fragile X Syndrome (FXS)

Overview

Fragile X Syndrome (FXS) is a genetic disorder that causes developmental delays, learning difficulties, and social and behavioural challenges. It is caused by a mutation in the FMR1 gene, which affects brain development. Symptoms may include anxiety, hyperactivity, speech issues, and physical disabilities such as a long face, flat feet or large ears. While there is no cure, therapies, medications, and a healthy lifestyle can help manage the symptoms and improve quality of life.

What is Fragile X Syndrome (FXS)?

Fragile X syndrome (FXS) is an acquired genetic disorder, causing behavioural changes, physical abnormalities and mental health problems in individuals. One may experience anxiety, ADHD, autism spectrum disorder, learning disabilities, developmental delays and intellectual disabilities. This condition is also known as Martin Bell syndrome, where the X chromosome appears “broken” or “fragile” when observed under a microscope.

Types of Fragile X Syndrome (FXS)

While FXS is usually diagnosed in children, the two other syndromes that may be diagnosed in adults include the following:

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): It occurs in male permutation carriers who are above the age of 50. Some common symptoms include tremour, memory problems, balance issues, cognitive problems, numbness in feet and hands, and unstable mood.

Fragile X-Associated Primary Ovarian Insufficiency (FXPOI): It occurs in female permutation carriers who are above 40 years old. Some common symptoms include impaired ovarian functions such as early menopause, infertility, and missed or unpredictable menstrual periods.

Symptoms of Fragile X Syndrome (FXS)

FXS causes developmental delays, learning disabilities, and behavioural and social problems in individuals. Intellectual disability may develop in both boys and girls. Affected individuals may experience symptoms including stuttering, social or general anxiety, depression, autism, hyperactivity, attention disorders, difficulty sleeping and seizures. Physical abnormalities can include an elongated face, flat feet, flexible or loose joints, protruding forehead, chin and ears.

FXS symptoms in each category are highlighted in the following table:

Intelligence Issues	Physical Features	Mental Health Problems	Behavioural Changes
Delayed development of nonverbal communication, low IQ, learning disabilities, difficulty in solving math problems, language processing issues	Flat feet, enlarged testicles after puberty, long, narrow face, large forehead, jaw and ears, crossed eyes, hypotonia	Anxiety, depression, obsessive-compulsive disorder	Social anxiety, ADHD, poor eye contact, sensory disorders, habit of biting hands, unable to pick up social cues

Causes of Fragile X Syndrome (FXS)

Fragile X syndrome (FXS) is caused by a genetic mutation of the FMR1 gene on the X chromosome. The gene provides instructions to the body for producing FMRP protein, which helps in the development of synapses. These synapses are specialised connections between a child's nerve cells, essential for relaying nerve impulses.

The gene mutation causes the CGG triplet to expand and multiply abnormally up to 200 times or more. These changes disrupt the child's nervous system, causing the symptoms of FXS. A carrier of FXS is at higher risk for developing other health conditions, including chronic pain, migraine, dementia, high blood pressure, sleep apnea, hyperthyroidism, depression and anxiety.

Diagnosis of Fragile X Syndrome (FXS)

Before conducting a test for fragile X syndrome, a healthcare provider may prescribe a physical exam of the child. They may ask questions related to the child's behavioural, social interactions and learning skills. Upon finding something suspicious, the doctor may collect a DNA sample from the child's blood or other tissues to help determine if the child has the FMR1 gene.

A genetic counsellor can help a pregnant parent examine the risk of passing on the mutated gene to their child by undergoing certain prenatal tests such as amniocentesis and chorionic villus sampling.

Treatment for Fragile X Syndrome (FXS)

Fragile X syndrome cannot be cured. However, treatment plans are available to help manage the symptoms of the condition, allowing patients to learn social and key language skills. A doctor may prescribe medications for behavioural disorders, which may commonly include methylphenidate (Ritalin), clonidine (Catapres), guanfacine (Intuniv), and selective serotonin reuptake inhibitor (SSRI), such as sertraline (Zoloft), duloxetine (Cymbalta), escitalopram (Lexapro), and paroxetine (Pail, Pexeva).

Medications for seizures or mood instabilities may include lithium carbonate and gabapentin (Neurontin). Aggression or obsessive-compulsive disorder may be treated by fluoxetine (Prozac®) or sertraline (Zoloft®) and citalopram (Celexa®).

A healthcare professional may recommend methylphenidate (Ritalin®, Concerta®), dextroamphetamine (Adderall®, Dexedrine®), venlafaxine (Effexor®) and nefazodone (Serzone®) for ADHD; and melatonin or trazodone (Desyrel®) for sleep-related issues. Psychotherapy may also be recommended to a child with FXSz helping with behavioural and coping skills.

Prevention of Fragile X Syndrome (FXS)

FXS cannot be prevented. However, genetic counselling and prenatal testing can help to evaluate the risk of passing on the condition to children. Early intervention and preventive care, including targeted therapies and physical activity, can help improve the overall well-being of children and young adults with Fragile X syndrome.

Myths and Facts Related to Fragile X Syndrome (FXS)

Here are some of the myths and facts about Fragile X Syndrome (FXS):

Myth 1: Fragile X syndrome is a gender-specific condition
Fact: While boys often show more severe symptoms due to having only one X chromosome, both boys and girls can have FXS.

Myth 2: Bad parenting causes fragile X syndrome
Fact: Fragile X syndrome is a genetic disorder that is caused by a mutation in the FMR1 gene. Parenting or other environmental factors do not play a role in this.

Myth 3: Individuals having FXS disorder will always have problems in learning
Fact: Individuals can learn effectively with tailored therapies, educational support and a structured learning environment.