FRAX - fragile X chromosome syndrome
The most common cause of genetically determined intellectual disability.
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About FRAX
Fragile X syndrome (FRAX) is associated with the occurrence of a dynamic mutation in the FMR1 gene, which results in inhibition of its expression and consequently lack of FMRP protein synthesis. FMRP protein activity is particularly important for the process of synaptic plasticity. Its deficiency leads to abnormal brain development, memory and learning problems, attention deficit disorders, hyperactivity, cognitive impairment and autism spectrum disorders. Fragile X chromosome syndrome can also cause premature expiration of ovarian function, leading to infertility in women.
Frequently asked questions
regarding fragile X chromosome syndrome
Fragile X Syndrome (FRAX) is a genetic disorder and is the most common familial form of intellectual disability. It occurs with a frequency of 1:4,000 – 1:6,000 male births and is caused by a mutation in the FMR1 gene located on the X chromosome. The protein encoded by this gene – FMRP – plays a very important role in the development of synapses, or connections between neurons. Its absence therefore impairs the maturation of nerve cells, which in the patient manifests itself in cognitive impair ment (mild to severe intellectual disability) and autism spectrum disorders . In addition, people affected by broken X chromosome syndrome can be observed:
- protruding ears
- prominent forehead
- narrow longitudinal face
- excessive mobility in the interphalangeal joints
- enlargement of the testicles (in men after puberty)
- flat feet
- disorders of muscle tone
The higher prevalence of FRAX syndrome in boys than in girls is related to the location of the FMR1 gene on the X chromosome. As is well known, women each have two X chromosomes in their karyotype (46, XX), while men have one X chromosome and one Y chromosome (46, XY). In a woman, therefore, there is always one normal X chromosome left, with the protein-coding FMR1 gene correctly . Therefore, in female individuals, symptoms of the syndrome are less frequent and milder. Men, on the other hand, do not have a second X chromosome with a normal copy of the gene, so the disease will manifest itself in them more often and be characterized by a more severe course.
The cost of the genetic test for broken X chromosome syndrome is £350.
The cause of FRAX syndrome is the presence of a dynamic mutation in the FMR1 gene, which inhibits the expression of this gene and results in a lack of FMRP protein for nerve cell maturation and synapse plasticity.
Yes, broken X chromosome syndrome is an inherited disease and is inherited in a dominant X chromosome-coupled manner. In practice, this type of inheritance means that a heterozygous sick mother passes the defective gene with a 50% probability to both her sons and daughters, while a sick father passes the defective gene to all his daughters, but no son.
Genetic testing is particularly indicated for children who have:
- autism spectrum disorders (delayed speech development, avoidance of eye contact, unwillingness to play with other children, hypersensitivity to external stimuli, such as touch)
- intellectual disabilities (cognitive process disorders and learning disabilities)
- dysmorphic features (pulled face, protruding ears, emphasized forehead).
Since broken X chromosome syndrome is an inherited disease and can be passed from one generation to the next, genetic counseling should also be extended to the patient’s family members.
Fragile X chromosome syndrome – causes of formation
Fragile X chromosome syndrome is caused by too many CGG trinucleotide repeats in the non-translated 5′ segment of the FMR1 gene. A healthy person has such repeats from 6 to 45. The number of repeats from 45 to 54 is the so-called “gray area.” In asymptomatic carriers, the number is between 55 and 200 triplet repeats. This is known as premutation. When the number of CGG triplet repeats exceeds 200 we are dealing with a full mutation, which is associated with the occurrence of a number of disorders.
Clinical manifestations of FRAX
Friable X chromosome syndrome is a genetic disorder coupled to the X chromosome. Since only one X chromosome is present in male individuals, the clinicalmanifestationsof FRAX in males are more severe than in females.
Broken X chromosome syndrome in male patients manifestsitself, among other things:
- delayed physical and speech development
- decreased muscle tone
- sensory disorders
- autistic traits
- moderate or severe intellectual disability
- learning difficulties
- motor stereotypy
- hyperactivity
- behavioral disorders
- attention deficit disorder
- large, protruding auricles
- elongated, narrow face
- enlargement of the testicles after puberty
- excessive flaccidity of the interphalangeal joints of the hands
- flat feet
- smooth, velvety skin
- epilepsy
Women, on the other hand, who are carriers of the full mutation, show much milder symptoms. The most common are:
- mild intellectual disability
- learning difficulties
- emotional disorders
- depression, anxiety, fear
- slightly elongated face
- enlarged auricles
- premature extinction of ovarian function
- infertility
Fragile X chromosome syndrome is diagnosed using genetic testing. At Gyncentrum Genetic Laboratory, we use modern molecular biology methods. FRAX prescreening is based on amplification of genomic DNA by polymerase chain reaction (PCR). The test detects the number of CGG triplet repeats in the non-translational region 5 ‘of the FMR1 gene.
Who should take the FRAX genetic test?
- Women with premature expiration of ovarian function
- Women unsuccessfully trying to have a child
- Women postponing the decision to have offspring
- People planning to have offspring
- Children with symptoms from the autism spectrum
- Patients with symptoms of intellectual retardation, i.e.: excessive mobility, low IQ, behavioral disorders, changes in physical appearance characteristic of FRAX
- Individuals in the family who have been confirmed to carry the defective FMR1 gene, or when a family member has troubling symptoms
Fragile X chromosome syndrome is an inherited disease. Since the development of adverse disorders occurs over several generations, genetic counseling should be provided not only to the affected person, but also to the entire family.
Why should I get tested for carrying the defective FMR1 gene?
- You will learn the possible cause of ovarian failure
- You will consciously plan the timing of your efforts to have a child
- You will find out whether your problems with conceiving a child are due to genetic conditions
- You will learn the cause of your child’s developmental disorders
- Your doctor will be able to assess your risk of having a baby with FRAX in the future
- You and your family members will receive genetic counseling
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Are you interested in the cost of FRAX genetic testing?
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