The modern rapid development of medicine has allowed mankind to discover many previously unknown diseases. Particularly important in the twentieth century was the deciphering of the genetic code, 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 the genetic material are known. A relatively new pathology is Martin-Bell syndrome, which has a fairly high percentage of childhood disability.
Martin-Bell disease - a syndrome or a neurological disorder?
Martin-Bell syndrome is a congenital pathology associated with fragility of the X chromosome. The concept of "fragility" means a visual sharp narrowing of the ends of the X chromosome. Such changes confirm the Martin-Bell syndrome. The photo of children on the left indicates a lag in psychomotor development, which tends to progress from early childhood.
Reasons
As you know, the normal human genotype is 46 chromosomes, two of which are sex X and Y. In women, respectively, the chromosome set will look like - 46 XX, and in men - 46 XY. Thesecarriers of genetic information consist of chains of repetitions of amino acids, which contain information about the structure and functions of a future living organism.
Martin-Bell disease (fragile X syndrome) develops due to changes in the X chromosome, so both women and men can suffer from it. The thinning of the X-chromosome site is due to a pathological increase in specific repeats of amino acid residues - cytosine-guanine-guanine (C-G-G). Such a combination of repetitions is present several times in other genes, but it is important, in fact, the number of these repetitions. Normally, it ranges from 29 to 31. In the case of Martin-Bell syndrome, this number 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. systems. The result becomes apparent after a short period of time after the birth of the child and is manifested by a delay in psychomotor development.
Manifestations
The number of repeats of cytosine-guanine-guanine causes various variants of the clinical manifestations of Martin-Bell's disease. The syndrome may have hidden forms. If the study reveals from 55 to 200 repetitions, a premutation occurs - borderline changes that make a person a carrier, but without visible changes in the nervous system. In mature and senile age, ataxic syndrome and primary ovarian failure in women may develop. At the same time, the probabilitytransmission syndrome is high. An intermediate state is also distinguished - this is from 40 to 60 nucleotide repeats, which is not clinically manifested in any way and can be inherited after several generations.
Inheritance
Genetics classify this disease as a group of pathologies linked to sex, 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. Very rarely, a premutational variant and carriage are possible in a man. Women are much more likely to be carriers of the disease, and pass on the "pathological" chromosome with the same probability for both daughters and sons. A sick father can only pass on the X chromosome to his daughters. The inheritance of the syndrome gradually increases from generation to generation, which is called the Sherman paradox. The clinical course of the syndrome is much more severe in men.
Symptoms
Martin-Bell syndrome, whose symptoms resemble autism, is not always recognized in time even by an experienced pediatrician or neurologist.
Clinical presentation may vary depending on the number of C-Y-H repetitions.
In the classic version, psychomotor retardation indicates a potential Martin-Bell syndrome. A photo of a child allows you to see the first characteristic signs of the disease. There is lethargy and discoordination of movements, muscle weakness develops. Quite often childrensuffer from autism. On examination, a neuropathologist reveals disorders in the functioning of the oculomotor nerves and some abnormalities in the functioning of the brain. With age, the situation worsens, the picture of mental retardation gradually increases.
Psychological disturbances are always present: the child often mutters to himself, shows grimaces unmotivatedly, often claps his hands, sometimes behaves very aggressively. These symptoms are somewhat reminiscent of schizophrenia. Another option is autism, which begins in early childhood.
Martin-Bell syndrome: signs
A specific sign in boys is enlarged testicles (macroorchism), but this can only be detected in puberty. At the same time, there are no endocrine disorders.
Changes in the appearance itself are relatively non-specific, but may lead the physician to seek the correct diagnosis. The child often has a large head, a long face, and a slightly beak-shaped nose. There are large sizes of the hands and feet, the fingers have a significantly increased range of motion. Often the skin has increased elasticity.
Manifestations of the premutational variant of the disease have certain characteristic features. The ataxic syndrome is characterized by the presence of tremor and memory impairment, especially short-term memory, mood changes and the gradual development of dementia with a decrease in cognitive functions (inability to read and understand speech). Symptoms are more common in mencarriers and has a more severe course compared to women.
For primary insufficiency of ovarian function, the appearance of premature menopause and impaired functioning of the pituitary-ovarian system is characteristic. The content of follicle-stimulating hormone increases, which leads to the disappearance of menstruation and the appearance of vegetovascular symptoms. The disease progresses gradually and requires hormone replacement therapy.
How to diagnose the syndrome
For an approximate determination of the disease in the early stages of a child, a cytogenetic method is suitable. The patient's cell material is taken and vitamin B₁₀ (folic acid) is added as a provocateur of changes in chromosomes. After some time, the study reveals a section of the chromosome with significant thinning, which indicates Martin-Bell disease, fragile X syndrome. This laboratory method is not accurate enough in the later 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 the Martin-Bell syndrome. Photo taken with an electron microscope shows an area of autosome thinning.
A separate, even more specific option is the combination of PCR with detection on capillary electrophoresis. This examination with high accuracy reveals the pathology of chromosomes in patients withataxic syndrome and primary ovarian failure.
Treatment
After PCR is performed and a diagnosis of Martin-Bell syndrome is made, treatment should begin as soon 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 the manifestations of psychomotor retardation, correcting changes in ataxic syndrome and hormonal support in primary ovarian failure.
Children with mental retardation and a confirmed PCR result are diagnosed with Martin-Bell Syndrome. Russia does not have medical institutions where rehabilitation is carried out for such children, so a pediatrician and related specialists are involved in the treatment. It is immediately worth noting that the treatment of children is more effective than adults. They use methods of cognitive-behavioral therapy, sessions with a psychiatrist on an individual basis, exercise therapy, light forms of psychostimulants. A relatively new area is the use of drugs based on folic acid, but long-term results are still being studied.
For adults, therapeutic therapy includes psychostimulants and antidepressants, constant dynamic monitoring is carried out by a psychiatrist and psychologist. In private clinics, sessions of microinjections of the drug "Cerebrolysin" and its derivatives, cytomedines (drugs "Lidase", "Solcoseryl") are carried out.
In ataxic syndrome, nootropics and blood thinners, angioprotectors and mixtures of amino acids are used. Primary ovarian failure in women is subject to correction with estrogens and herbal remedies.
Effectiveness of treatment is relatively low, but it allows to slow down the development of the disease for some time.
Prevention
Pregnancy screening is the only way to prevent. In the developedcountries of the world, examinations have been introduced that make it possible to detect Martin-Bell syndrome in the early stages and terminate a pregnancy. An alternative option is in vitro fertilization, which can help ensure that the unborn child inherits a "he althy" X chromosome.
