Health Watch (Fragile X Syndrome)

Fragile X Syndrome Genetic Disorder — Spot the Signs in Early

Childhood

Speech delays, deferred maturity, learning difficulty, social withdrawal, attention deficit, hyperactivity, autistic behaviour, seizures, sleep trouble and slow performance in daily chores may give hints of Fragile X Syndrome at a tender age. Identify these red flags as soon as possible, suggest doctors.

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By PRAMITA BOSE

Three-year-old Varun started showing learning disabilities when he was admitted in a playschool. His parents were visibly worried about his lack of cognitive skills and common aptitude. 10-yearold Eshani had developed social dysfunction since she was a toddler and that intensified with age as she mostly kept to herself and seldom mingled with friends, peers and family relations. Was her behaviour a telling sign of autism? Teenager Ishaan too suffered from mental inertia, resistance to change and attention deficit as he struggled to cope with study pressure and manage his daily activities.

All these complications could be a serious cause for concern and need to be addressed immediately. Psychologists and neurologists call this condition Fragile X Syndrome (FXS), a genetic disorder.

Facts About FXS

Eminent consultant neurologist Dr Suhas VP of Bangalore Hospital at Jayanagar and Kengeri decodes Fragile X Syndrome (FXS) as “a hereditary genetic disease that impedes rational and emotional development as well as upsets behavioral patterns.” “It results from a gene (FMR1) mutation located on the X chromosome, which thwarts protein (FMRP or Fragile X Mental Retardation Protein) secretion essential for brain function and development,” he explains.

Incidentally, FXS is the most common inherited cause of cerebral void and is also linked to autism spectrum disorder. It can lead to a gap in social communication or interactive skills indicating restricted mannerisms or repetitive interests. Such problems might vary in degree of severity from person to person.

Psychoanalyst Dr. Malini Saba, founder of the Saba Family Foundation, states that “FXS can affect people in multiple ways that may get reflected in how they learn, speak, handle feelings or react to the world and people around them. It’s a reminder of our one of the most delicate and complex organs — the brain. Even a tiny shift in the DNA can end up shaping our feelings — how we and our curiosity level works, how we deal with stress and learn to trust.”

Tracing the Roots

FXS is caused by an expanding DNA sequence — CGG repeats (specific DNA sequence pattern within a gene that is repeated multiple times) — in the FMR1 gene on the X chromosome. When the number of repeats exceeds 200, the gene becomes methylated and inactive, halting production of FMRP, a protein responsible for brain development.

This alteration can be passed down to several generations in a family and women can be the potent carriers without showing symptoms. The signs may aggravate with the gene’s capacity loss or depletion of its characteristic properties.

Dr Saba confirms that “this isn’t something that anyone can catch like a virus or which partners can transmit to each other. It’s not an infection that a person may contract. It’s written in the DNA right from the start, from the moment of conception of a baby.”

Spotting the Differences

Symptoms of FXS include intellectual handicap, speech delays, hyperactivity, anxiety, social withdrawal and recurring behaviours. Some individuals also grow sensitive to light or sound and are inflexible to adapt to any unfamiliarity. Furthermore, seizures and sleep disturbances may occur in a few cases. Behavioral signs often resemble traits of autism and children may exhibit hand-flapping, poor eye contact and impulsiveness. While the physical hints might not be apparent in early stages, neuroimaging like 3T MRI {Magnetic Resonance Imaging (MRI) machine using a magnetic field strength of 3 Tesla} can reveal subtle brain switches tied to these developmental obstacles.

“Delays in talking and understanding language, tardy progress in generalised learning and an overall slower development can hamper normal mental growth or maturity in a child. A lot of kids or adults with Fragile X also deal with anxiety. Many show autism like behaviours, namely repeating words or phrases or feeling awkward in social situations. Some also have ADHD or get really overwhelmed by loud noises or how certain clothes feel,” sums up Dr Saba.

Vulnerable Age and Slow Progress

FXS signs often emerge in infancy or early childhood, typically between 1 and 3 years of age. Delayed milestones like crawling, walking or speaking are usually the initial indicators.

As kids grow, they tend to get overloaded with life’s regular tasks like studying, retaining focus and controlling their ever-oozing sentiments. They might feel under the pump to meet certain expectations and those undue social demands set as an agenda to them. This could suffocate and burden a child with the onus of pushing the limits.

Many succumb to this stress and fumble in social settings, their confidence ebbs and they appear extremely shy, jaded and edgy, in addition to facing trouble adjusting to their backbreaking routines. Early assessments and an advanced MRI can help pinpoint brain anomalies allied to this sluggish behaviour and aid in timely intervention.

Usually, signs are noticed before age two. A child may get really nervy if something changes suddenly or have a meltdown over a noisy place or a scratchy tag on a shirt. Even tiny changes in a day-to-day schedule can piss an FXS-affected child off. He or she could feel lost when other kids are playing together. “It’s so important for parents to know and understand that this is not their pretension. It’s their way of trying to handle the situation when they feel overwhelmed,” notes Dr Saba.

Unique Marks

A person with FXS syndrome develops a specific type of appearance, which is easily identifiable. Some individuals with FXS, particularly males, develop distinct physical features as they age.

“These can include a long, narrow face, prominent ears, a broad forehead, a high-arched palate and a prominent jawline or a chin. Post-pubertal males may have enlarged testicles. These features are more noticeable during adolescence or adulthood and may not be evident in younger children. However, diagnosis is primarily based on genetic and neurological analyses as physical traits alone are not always reliable,” Dr Suhas describes in detail.

Detection

FXS is diagnosed using a DNA blood test that measures the frequency of CGG repeats in the FMR1 gene. This test determines whether the gene is mutated or silenced. In case of a slackened progress or persistent neurological symptoms, a 3T MRI may be useful to evaluate structural brain differences or abnormalities, such as enlarged ventricles or underdeveloped white matter regions.

Treatment

Talking us through its treatment process, Dr Suhas confirms that “while there is no cure for FXS, its treatment targets symptom management via a multidisciplinary approach. Early intervention is key. Behavioral, occupational and speech-language-oriented therapies are necessary alongside tailored educational support. Medications may be prescribed for anxiety, attention issues or mood instability. For individuals with seizures, anticonvulsants may be required. For brain changes linked to specific functional delays, therapies can be further customised to an individual's neurological profile.

Male Versus Female Ratio

FXS affects men more fiercely. This is because males have only one X chromosome along with a Y variety. So if their FMR1 gene is defective, they lack a backup copy. Females have two X chromosomes and one functioning gene can partially compensate for the mutated one, often resulting in a milder version or even disappearing completely. Males are more likely to experience significant thinking blockade and behavioral setbacks, while females may confront subtle learning or emotional difficulties.

No Road to Recovery?

“FXS is not curable because it emanates from a permanent mutation in the DNA that shuts off the FMR1 gene. Current evolutions in science have not yet found a way to reverse or repair this genetic shift. However, research is underway in gene therapy and protein replacement,” reasons Dr Suhas.

Meanwhile, early detection and consistent therapeutic assistance can significantly improve the overall quality of life, helping individuals develop skills in interpersonal exchanges, gain independence and acquire social abilities.

Care to Ensure a Placebo Effect

There are certain therapies and medical interventions involved in managing FXS symptoms and providing palliative care to a patient. Multiple therapies are tailored to an individual’s needs. Behavioural therapy helps with emotional regulation and social skills, speech therapy improves communication, and occupational therapy enhances motor and sensory integration.

“There’s no cure for Fragile X but getting help timely really does make a huge difference. Speech therapy can help patients communicate better. Occupational therapy is great for handling textures, sounds and coordination, while behavioural therapy teaches ways to cope and helps with social skills. Sometimes doctors prescribe medicines for anxiety, mood swings or hyperactivity,” informs Dr Saba.

“But honestly, what matters most is having a home that feels safe, steady, calm and loving. Kids with Fragile X do best when there’s a simple roster, things are straight and explained clearly, every little crease is ironed out to make their life’s journey less bumpy and above all, when they know they are not being judged and are loved exactly as they are, and that’s what helps them grow and feel secure, just like any other child,” she further enlightens.

Medications may be administered for conditions like anxiety, ADHD (attention deficit hyperactivity disorder) or seizures. In specific cases, neuroimaging like 3T MRI can aid in understanding brain function and devising personalised therapeutic plans or setting guidelines. A holistic, coordinated approach between healthcare, school and family support systems is vital for long-term improvement.

Life Expectancy

People afflicted with FXS generally have a normal life span. However, their quality of life may depend on how adeptly associated conditions, such as seizures, anxiety or heart issues are managed. Regular health monitoring, therapy and support systems can help individuals lead self-reliant or semi-independent lives. Lifespan is more likely to be influenced by coexisting medical issues rather than the syndrome itself, and comprehensive care is essential to ensure safety and well-being across all life stages.

Prescription for FXS Patient

There’s no specific medication to treat FXS itself but several drugs are recommended to manage related symptoms. Stimulants like methylphenidate help with dearth of motivation and hyperactivity disorder. SSRIs (a class of antidepressants applied to treating various mental maladies), such as fluoxetine, are used for anxiety and depression. Antipsychotics like risperidone may be used for severe behavioural issues, while anticonvulsants are suggested if there are complaints of seizures. Drug selection depends on individual needs and responses, often guided by the ongoing behavioural appraisals and when necessary, neurological evaluations.

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