The modern rapid development of medicine has allowed mankind to discover many previously unknown diseases. The decoding of the genetic code was especially important in the 20th century , which made it possible to identify the causes of many gene and chromosomal pathologies. More than 3,000 diseases associated with quantitative and qualitative changes in genetic material are known. A relatively new pathology is Martin-Bell syndrome, which has a fairly high percentage of childhood disabilities.
Martin-bell disease - syndrome or neurological disorder?
Martin-Bell Syndrome is a congenital pathology associated with fragility of the X chromosome. The term "fragility" means a sharp visual narrowing of the ends of the X chromosome. Such changes confirm Martin-Bell syndrome. The photo of children on the left indicates a lag in psychomotor development, which tends to progress from early childhood.
Causes
As you know, the human genotype in the norm is 46 chromosomes, two of which are sex X and U. For women, respectively, the chromosome set will look - 46 XX, and for men - 46 X. These carriers of genetic information consist of chains of amino acid repeats, which contain information about the structure and functions of the future living organism.
Martin-Bell disease (fragile X-chromosome syndrome) develops due to changes in the X-chromosome, therefore, both women and men can get it. The thinning of the X-chromosome is due to a pathological increase in specific repeats of amino acid residues - cytosine-guanine-guanine (C-H-G). This combination of repetitions is present several times in other genes, however, the number of these repetitions is important. Normally, it ranges from 29 to 31. In the case of Martin-Bell syndrome, this amount is sharply increased and can occur from 230 to 4000 times, which leads to an increase in the chromosome and impaired functioning of a special gene - FMR1, which is responsible for the proper functioning and development of the nervous system. The result becomes apparent after a short period of time after the birth of the baby and is manifested by a delay in psychomotor development.
Manifestation options
The number of repetitions of cytosine-guanine-guanine causes various variants of the clinical manifestations of Martin-Bell disease. The syndrome may have hidden forms. If the study reveals from 55 to 200 repetitions, a premutation arises - borderline changes that make a person a carrier, but without visible changes in the nervous system. In adulthood and senile age, ataxic syndrome and primary ovarian failure in women can develop. Moreover, the likelihood of transmission of the syndrome is high. An intermediate state is also distinguished - it is from 40 to 60 nucleotide repeats, which is clinically not manifested in any way and can inherit through several generations.
Inheritance
Genetics attribute this disease to a group of pathologies linked to the floor, that is, with the X chromosome. In men, the disease manifests itself more often and more distinctly, since their genotype contains one X chromosome. In women, pathology develops in the presence of both "pathological" X-autosomes. It is very rare for a man to have a pre-mutation option and a carriage. Women are much more likely to be carriers of the disease, and they transmit the “pathological” chromosome with the same probability for both daughters and sons. A sick father can pass the X chromosome only to daughters. The inheritance of the syndrome is gradually increasing from generation to generation, which is called the Sherman paradox. The clinical course of the syndrome is significantly more severe in men.
Symptoms
Martin-Bell syndrome, the symptoms of which resemble autism, cannot always be recognized in time even by an experienced pediatrician or neurologist.
The clinical picture may differ depending on the number of repetitions of TS-G-G.
In the classic version, a delay in psychomotor development indicates a potential Martin-Bell syndrome. A photo of the child allows you to see the first characteristic signs of the disease. Inhibition and discoordination of movements are observed, muscle weakness develops. Quite often, children have autism. On examination, a neurologist reveals disturbances of the oculomotor nerves and some abnormalities in the brain. With age, the situation worsens, the picture of mental retardation gradually grows .
Mental disorders are always present: the child often mumbles to himself, unmotivated shows grimaces, often claps his hands, sometimes behaves very aggressively. Such symptoms are somewhat reminiscent of schizophrenia. Another option is autism, which begins to develop in early childhood.
Martin-Bell Syndrome: Symptoms
A specific feature in boys is increased testicular size (macroorchism), but this can only be detected in the puberty period. However, any endocrine disorders are absent.
Changes in the appearance itself are relatively nonspecific, but may prompt the doctor to search for the correct diagnosis. The child often has a large head, an elongated face and a slightly beak-curved tip of the nose. Large sizes of hands and feet are noted, fingers have a significantly increased range of motion. Often the skin has increased elasticity.
Manifestations of the pre-mutation variant of the disease have certain characteristic features. Ataxic syndrome is characterized by the presence of tremor and impaired memory, especially short-term, mood changes and the gradual development of dementia with a decrease in
cognitive functions (inability to read and understand speech) are noted. Symptoms develop more often in male carriers and have a more severe course compared to women.
The primary failure of ovarian function is characterized by the appearance of premature menopause and impaired functioning of the pituitary-ovary system. The content of follicle-stimulating hormone increases, which leads to the disappearance of menstruation and the appearance of vegetovascular symptoms. The disease gradually progresses and requires hormone replacement therapy.
How to diagnose a syndrome
For a rough definition of the disease in the early stages, the child will use the cytogenetic method. The patient’s cellular material is taken and vitamin B₁₀ (folic acid) is added as a provocateur of changes in the chromosomes. After some time, the study reveals a portion of the chromosome with significant thinning, which indicates Martin-Bell disease, a fragile X-chromosome syndrome. This laboratory examination method is not accurate enough in the late stages, due to the widespread use of multivitamins, which include folic acid.
Highly specific is the polymerase chain reaction (PCR), which allows you to decipher the structure of amino acid residues in the X chromosome and indicate Martin-Bell syndrome. An electron microscope photo shows an autosome thinning area.
A separate, even more specific option is the combination of PCR with detection by capillary electrophoresis. This examination reveals with high accuracy the pathology of chromosomes in patients with ataxic syndrome and primary ovarian failure.
Treatment
After PCR and the diagnosis of Martin-Bell Syndrome, treatment should be started as early as possible.
Since the disease is congenital and has a chromosomal origin, therapy is reduced to alleviating the main symptoms of the disease.
The treatment regimen is aimed at minimizing manifestations of a delay in psychomotor development, correction of changes in ataxic syndrome, and hormonal support in primary ovarian failure.
Children with mental retardation and confirmed PCR are diagnosed with Martin-Bell Syndrome. Russia does not have medical facilities where they provide rehabilitation for such children, therefore, a pediatrician and related specialists are involved in the treatment. It is immediately worth noting that treating children is more effective than adults. Applied methods of cognitive-behavioral therapy, classes with a psychiatrist individually, exercise therapy, mild forms of psychostimulants. A relatively new direction is the use of folic acid preparations, but long-term results are still being studied.
For adults, therapeutic therapy includes psychostimulants and antidepressants, constant dynamic monitoring by a psychiatrist and psychologist is carried out. Private clinics conduct microinjection sessions of the drug Cerebrolysin and its derivatives, cytomedines (Lidaza, Solcoseryl medicines).
In ataxic syndrome, nootropics and blood thinners, angioprotectors, and amino acid mixtures are used. Primary ovarian failure in women is subject to correction by estrogens and herbal remedies.
The effectiveness of treatment is relatively low, however, it allows for a while to slow down the development of the disease.
Prevention
The only way to prevent this is to screen pregnant women. In developed
Examinations have been introduced to countries around the world to detect Martin-Bell syndrome in the early stages and terminate pregnancy. An alternative option is in vitro fertilization, which may contribute to the fact that the unborn child inherits a “healthy” X chromosome.