FragileX synd rome is classified as a rare disease with a genetic basis. The causes of the disease are still unknown - it is difficult to pinpoint what specifically contributes to the occurrence of this genetic defect.
Table of contents:
- What is fragile X chromosome syndrome
- How common is the disease?
- Symptoms
- Risk factors
- Why do women get the disease more easily?
- Inheritance
- How to detect the disease
- Prognosis
What is fragile X syndrome
FXS or FRAX, or fragile X chromosome syndrome, is one of the rare genetic diseases. The condition is associated with the occurrence of a mutation in the FMR1 gene, which results in reduced or absent FMRP protein synthesis. Mutations can arise spontaneously, under the influence of external factors such as strong radiation. However, it is difficult to pinpoint the specific cause of mutations within the FMR1 gene. The FMRP protein, which is not formed in sufficient quantities in the patients' bodies, is essential for normal brain development.
How common is the disease?
The disease is rare, estimated to affect 1/4,000 live-born children. Importantly, FXS can present with a variable clinical phenotype, meaning that it manifests differently in girls and boys. In males, the disease makes itself known as early as childhood, when motor delay and speech development problems are diagnosed. Intellectual and behavioural disorders are added to this. It should be noted that intellectual disorders can range from mild to severe. Similarly for behavioural disorders, which can take a variety of forms. Intellectual dis orders are estimated to affect approximately 50% of women diagnosed with fragile X syndrome. In both sexes, a narrow and elongated face, slightly protruding ears, prominent forehead, flat feet and, in post-pubertal males, macroorchidism, i.e. enlargement of the testes, are additionally observed.
Symptoms
Symptoms that should worry parents of young children include the child's 'limpness', problems with sitting up and turning sideways, late speech development, avoidance of eye contact, hypersensitivity to touch, hyperactivity, fits of aggression and rage, gastro-oesophageal reflux, recurrent ear infections. The older the child gets, the more severe the symptoms can become: additional difficulties with concentration, autistic symptoms, flat feet or limpness of the interphalangeal joints in the hands appear.
Risk factors
To date, scientists have not been able to clearly pinpoint what causes the mutation and consequently the disease. Research indicates that 1 in 5,000 men and 1 in 8,000 women may be a carrier of... a permutation! Which means that, under the influence of an 'activator', a defective gene can be passed on to a child.
Why do women get sick more easily?
Women have two XX sex chromosomes, men XY. When there is a mutation in the X chromosome, in women there is a second, properly functioning chromosome which, as it were, takes over the role of both chromosomes. The situation is more difficult in men who have one X chromosome - when it is burdened with a mutation, there is no possibility of it taking over its function.
Inheritance
The disease is hereditary, linked to gender. Women and men each have 23 pairs of chromosomes, 22 'same sex' pairs and one pair that determines sex (female XX, male XY). It is in the 23 pairs of chromosomes that the mutation occurs, resulting in the condition known as fragile X chromosome syndrome. Mutation of the FMR1 gene is classed as a dynamic mutation, meaning that the number of defective repeats within the gene increases as it is passed on to the next generation (when the mutation is passed on by the mother). Importantly, the greater the permutation (i.e. the more specific repeats the mother's gene sequence contains), the greater the risk of the child developing a full mutation. Interestingly, in the case of fragile X syndrome, there is the so-called Sherman paradox, whereby the risk of developing the disease among the siblings of a person with a so-called permutation (without symptoms of the disease) is significantly lower than for the grandchildren and great-grandchildren of that person.
Genetic code, photo: panthermedia
In the family history, it is worth noting cases of early menopause in women or cases of FXTAS syndrome in men, characterised by trembling of the limbs, Parkinson's disease-like symptoms, rigidity, bladder dysfunction, erectile dysfunction or impotence.
How to detect the disease
The disease can only be diagnosed by genetic testing. Genetic testing detects mutations in the FMR1 gene and thus assesses whether the child has a deficiency in the protein that codes for the gene. Venous blood is taken for the test, which is sent to a laboratory that specialises in carrying out genetic tests. In families with a history of the disease, prenatal testing during pregnancy is recommended to examine the developing baby and assess whether the child is affected.
Prognosis
Treatment is based primarily on the implementation of symptomatic treatment and the use of therapy. It is not possible to 'fix' the damaged gene. In patients whose first symptoms appear in early childhood, it is recommended to see a speech therapist, a psychologist and sometimes to establish individual teaching in order to adapt the educational programme to the child's real possibilities. Depending on the severity of the symptoms, the child should remain under the care of a specialist. The key to successful therapy is, above all, early recognition! Prompt action to implement therapy will allow the child's dysfunction to be reduced and life to be relatively normal.
