An overview of "Fragile X syndrome"
An overview of "Fragile X syndrome"
Introduction
Fragile X syndrome, or Martin Bell syndrome, is a genetic condition that is more commonly thought of as a single gene, although the fracture area may also be seen under a microscope.
This syndrome is one of the most common causes of hereditary retardation and includes a range of developmental problems such as learning disabilities and cognitive impairment.
The prevalence of Fragile X Syndrome is about 1 in 2 men, and one case is in every 8,000 women, and about one in 260 women carries the FXS gene.
Fragile X disease is so named because in the chromosomal range of some infected people, a fragile spot is seen at the end of the long arm of the X chromosome.
Signs and Symptoms of Fragile X Syndrome:
None of the people with Fragile X Syndrome show the same symptoms, but there are a number of general symptoms in all people.
It is usually more severe in men than in women.
Intelligence and Learning: Most men with Fragile X Syndrome have mild to moderate mental retardation, while only about half of women with the condition are mentally disabled.
It should be noted that seizures occur in about 2% of men and 5% of women with the disease.
Socio-Emotional Behaviors: Most children with Fragile X Syndrome have behavioral problems, anxiety, and hyperactive behaviors such as restlessness as well as attention deficit hyperactivity disorder (ADHD), fear of new situations, and so on.
Many children, especially boys, may be aggressive.
Girls may be embarrassed and shy about communicating with new people.
About one-third of people with fragile X also show features of autism, which affects communication and social interaction.
Physical and physical characteristics: Most men and half of women with fragile X syndrome have significant physical characteristics that show up with age.
These features include a long, narrow face, large forehead, large ears, prominent jaws, usually very flexible fingers, excessive flexibility and looseness of joints and all kinds of bone problems, flat feet, and large testicles in men after puberty. Be.
Language and speech: Most boys with Fragile X Syndrome have a lot of speech and language problems.
They may not speak clearly or may be stuttering.
Cause of illness:
The hereditary pattern of Fragile X syndrome is X-dependent.
The disorder is caused by a mutation in the FMR1 gene (Fragile X Mental Retardation 1) located on the X chromosome and is associated with increased triple nucleotide repetition of CGG during eugenosis.
In approximately 2% of patients with fragile X syndrome, FMR١ gene function is completely impaired.
This gene encodes a protein called FMRP, which regulates the production of other proteins and plays an important role in the development of nerve synapses that establish specialized connections and connections between nerve cells.
Almost all cases of Fragile X Syndrome occur due to mutations in the upstream FMR١ gene, followed by the expansion of the repetitions of the three CGG nucleotides within the gene and its abnormal methylation.
The frequency and repetition pattern of CGG in a person's DNA can vary.
Typically, this section of DNA shows ten to fifty repetitions.
In people with Fragile X Syndrome, these recurrences occur more than twice.
The abnormal spread of CGG repetitions of the FMRM gene causes the gene to be shut down, thus preventing the production of FMRP protein.
Dr. Sarang Younesi, [08.06.19 18:51]
Continuation of the cause of the disease:
The severity of the disorder is usually directly related to the number of recurrences.
- Normal: If there are 44 repetitions or less, the person is normal;
- Border: In the presence of 55-45 repetitions, the person is in the border state;
- Pre-mutant carrier or pre-mutation: If the number of repetitions is between 200-55, the person is in the pre-mutant (carrier) state.
These people are mentally normal, but may also experience emotional problems such as anxiety or depression.
- Patient: People with 200 and more recurrences (complete mutations) show symptoms of fragile X syndrome.
This disorder has anticipation features. This means that in transmission to future generations, the severity of the disease will be higher and the age of onset of the disease will be lower.
People with 55-45 repetitions who are in a borderline situation will not be at risk for having infected children; But there is a possibility that grandchildren will suffer and their consequences.
Pre-mutant carriers often do not show the phenotype of the disease.
But 50% of pregnant women, as well as other women in the family, may have early ovarian failure, premature menopause, or birth defects.
Some children with premutation may also show learning disabilities and autism.
In the case of women who have pre-mutated genes, there is a significant risk that pre-mutations will increase in size during meiosis, and repetitions will exceed CGG, creating a complete mutation (in gamete) that will be passed on to the next generation. Be.
People with premutation are at increased risk for a number of disorders called brittle X-ray disorders.
These disorders include primary ovarian failure (FXPOI) in women and X syndrome with concomitant tremor / ataxia (FXTAS) in men.
To diagnose the disease, genetic counseling is first performed by a geneticist; In patients with mental retardation, one of the recommended tests is the Fragile X Syndrome diagnosis test.
It should be noted that the diagnosis is only confirmed by genetic testing.
In the genetic laboratory, cytogenetic diagnosis can be performed using a special culture medium and molecular diagnosis through CGG Expansion Analysis and determining the number of CGG repetitions.
However, as mentioned above, molecular diagnostic methods are preferable to cytogenetic methods.
In a female carrier, there is a possibility of recurrence and transmission of the pathogenic gene to children.
However, when the X chromosome is inherited from the father, the repetition does not increase from pre-mutation to complete mutation.
Therefore, the daughters of the carrier man are in a state of transport, and it is possible for them to have infected children, but his sons will be healthy.
In female carriers, if the number of repetitions is less than 70, the probability of becoming a complete mutation in the next generation is 10%, if the number of repetitions is 90-70, the probability of becoming a complete mutation is 75%, and if the number of repetitions is more than 90, this probability is It reaches 90%.
Review Indications:
In some cases, the likelihood of transmission increases; Including:
1- History of the presence of fragile X syndrome in the family
2- History of mental retardation with unknown cause in the family
3. History of premature menopause, premature ovarian failure, or reproductive disorders with elevated FSH levels
4 - History of autism, hyperactivity or attention deficit disorder in the family
5. History of ataxia or tremor without known cause in the family
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treatment:
There is currently no cure for this syndrome; However, speech therapy, occupational therapy, and behavioral therapy can be helpful in resolving many behavioral problems and cognitive issues caused by Fragile X Syndrome.
In addition, new drug findings could be helpful in relieving aggression, anxiety, hyperactivity, and lack of concentration.
Comprehensive and complete genetic counseling will be provided by an expert and experienced genetic counselor in the diagnosis of the disease and prevention of recurrence of the child with the help of a physician.
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