Fragile X syndrome

Fragile X syndrome is an inherited disorder that is the most common cause of intellectual disability. People with fragile X syndrome experience behavioral, physical, intellectual, and mental health symptoms, such as:

• Developmental delay
• Learning disabilities
• Anxiety
• Attention deficit/hyperactivity disorder
• Autism spectrum disorders

Fragile X syndrome gets its name from a condition in which the X chromosome appears “fragile” or “broken” when examined microscopically. It is also called Martin-Bell syndrome.

Frequency

The exact number of patients with fragile X syndrome is not recorded, although statistics show that the incidence of the disease is 1:11 in women and 000:1 in men.

Symptoms

The symptoms of fragile X syndrome depend on the degree of behavioral, physical, intellectual, and mental retardation:

Intellectual disability

• Learning disability
• Low IQ, which decreases further with age
• Delay in early developmental milestones
• Delayed development of nonverbal communication (facial expressions, body language)
• Delayed speech development
• Impairment of ability to calculate

mental health problems

• Anxiety
• Depression
• Obsessive-compulsive behaviors (obsessive rituals)

Physical development delay

• Long, elongated face
• Big forehead
• Pronounced lower jaw
• Big ears
• Sielme
• Hyperelastic finger phalanges
• Flat feet
• Enlargement of the scrotum (after puberty)
• Deep palatine arch
• Decreased muscle tone

behavioral disorders

• Attention deficit hyperactivity disorder (ADHD).
• Social anxiety and shyness
• Self-harm of limbs
• Lack of eye contact
• Sensory disorders — hypersensitivity to touch, noise, food, certain textures, crowds
• Social skills deficit

reasons

The cause of the disease is a mutation on the X chromosome.  FMR1 Gene mutation. This gene ensures the synthesis of the FMRP protein, which plays a crucial role in the formation of neural synapses (connections) and the full mental development of a person.

FMR1 A gene mutation is an expansion of the CGG triplet (DNA sequence) repeats in its composition. In typical cases, the frequency of CGG triplet repeats is from 5 to 40, but in fragile X syndrome it exceeds 200. This leads to deactivation of the gene, a deficiency of the protein synthesized by it, which is reflected in the delay in the child's mental development.

Inheritance type

Fragile X syndrome is an X-linked dominant condition, meaning the gene is located on the X chromosome and only one copy of it is sufficient for the disease to develop.

Fragile X syndrome is more common in boys because they only have one X chromosome. The symptoms are also more pronounced. Because women have 2 X chromosomes and are more likely to have one healthy chromosome, the symptoms are milder, or often not present at all.

In some cases, certain health issues may also manifest themselves in carriers. Carriers of the mutation have a much higher risk of developing pathologies such as:

• Premature menopause (before age 40)
• dementia
• arterial hypertension
• Depression
• Anxiety
• Migraine
• Hypothyroidism
• Chronic pain syndrome
• Sleep apnea

Complications

• heartbreak
• sleep disturbance
• Irritability and aggression
• Self-harming behavior
• Obesity

Diagnosis

Diagnosis of the disease is based on DNA testing to detect mutations in the FMR1 gene. Screening for carrier status of the gene mutation is also important.

In boys, the diagnostics is made on average at the age of 3, and in girls slightly later, at the age of 4. Symptoms begin to appear at the age of 12 months.

Rarely, fragile X syndrome may be diagnosed in adulthood:

• Fragile X-associated tremor/ataxia syndrome: Symptoms include tremors in the limbs, impaired balance while walking, mood instability, memory loss, cognitive impairment, sensory loss in the limbs, and more.
• Fragile X-associated primary ovarian insufficiency: Symptoms include infertility, menstrual irregularities, and premature menopause.

Treatment

Fragile X syndrome cannot be cured, although symptomatic treatment can alleviate the general condition.

Prevention

Genetic diseases are virtually impossible to prevent. Genetic disease carrier screening and genetic counseling are important for pregnancy planning and managing the risks of developing the disease.

Laboratory "Synevo" offers screening for genetic diseases:

Source:

https://my.clevelandclinic.org/health/diseases/5476-fragile-x-syndrome

n.manjaparashvili@synevo.ge