45 chromosomes in humans disease. Chromosomal diseases: what is it. ME2CP duplication syndrome

Chromosomal diseases are a large group of congenital hereditary diseases. They occupy one of the leading places in the structure of human hereditary pathology. According to cytogenetic studies among newborns, the frequency of chromosomal pathology is 0.6-1.0%. The highest frequency of chromosomal pathology (up to 70%) was recorded in the material of early spontaneous abortions.

Consequently, most chromosomal abnormalities in humans are incompatible even with the early stages of embryogenesis. Such embryos are eliminated during implantation (7-14 days of development), which is clinically manifested as a delay or loss of the menstrual cycle. Some embryos die shortly after implantation (early miscarriages). Relatively few variants of numerical chromosome anomalies are compatible with postnatal development and lead to chromosomal diseases (Kuleshov N.P., 1979).

Chromosomal diseases appear as a result of damage to the genome that occurs during gamete maturation, during fertilization, or in the early stages of zygote cleavage. All chromosomal diseases can be divided into three large groups: 1) associated with impaired ploidy; 2) caused by a violation of the number of chromosomes; 3) associated with changes in the structure of chromosomes.

Chromosome anomalies associated with ploidy disorders are represented by triploidy and tetraploidy, which occur mainly in the material of spontaneous abortuses. Only isolated cases of the birth of triploid children with severe malformations that are incompatible with normal life activity have been noted. Triploidy can occur both as a result of digeny (fertilization of a diploid egg by a haploid spermatozoon), and due to diandry (the reverse version) and dyspermy (fertilization of a haploid egg by two spermatozoa).

Chromosomal diseases associated with a violation of the number of individual chromosomes in a set are represented either by a whole monosomy (one of the two homologous chromosomes in the norm) or a whole trisomy (three homologues). Whole monosomy in live births occurs only on the X chromosome (Shereshevsky-Turner syndrome), since most monosomies on the remaining chromosomes of the set (Y chromosome and autosomes) die at very early stages of intrauterine development and are quite rare even in the material of spontaneously aborted embryos and fetuses.

However, it should be noted that monosomy X with a fairly high frequency (about 20%) is detected in spontaneous abortions, which indicates its high prenatal mortality, which is over 99%. The cause of the death of embryos with monosomy X in one case and the live birth of girls with Shereshevsky-Turner syndrome in another is unknown. There are a number of hypotheses explaining this fact, one of which links the increased death of X-monosomal embryos with a higher probability of manifestation of recessive lethal genes on a single X chromosome.

Whole trisomies in live births occur on chromosomes X, 8, 9, 13, 14, 18, 21 and 22. The highest frequency of chromosomal disorders - up to 70% is observed in early abortions. Trisomy on chromosomes 1, 5, 6, 11 and 19 are rare even in abortive material, which indicates the great morphogenetic significance of these chromosomes. More often, whole mono- and trisomies on a number of chromosomes of a set occur in mosaic state both in spontaneous abortions and in children with CMHD (multiple congenital malformations).

Chromosomal diseases associated with a violation of the structure of chromosomes represent a large group of syndromes of partial mono- or trisomy. As a rule, they arise as a result of structural rearrangements of chromosomes present in the germ cells of the parents, which, due to disruption of recombination processes in meiosis, lead to the loss or excess of chromosome fragments involved in the rearrangement. Partial mono- or trisomies are known for almost all chromosomes, but only a few of them form clearly diagnosed clinical syndromes.

The phenotypic manifestations of these syndromes are more polymorphic than those of whole mono- and trisomy syndromes. This is partly due to the fact that the size of chromosome fragments and, consequently, their gene composition, can vary in each individual case, as well as the fact that in the presence of a chromosomal translocation in one of the parents, partial trisomy on one chromosome in a child can be combined with partial monosomy on the other.

Clinical and cytogenetic characteristics of syndromes associated with numerical chromosome anomalies.

1. Syndrome Patau (trisomy on chromosome 13). First described in 1960. Cytogenetic variants can be different: whole trisomy 13 (nondisjunction of chromosomes in meiosis, in 80% of cases in the mother), translocation variant (Robertsonian translocations D / 13 and G / 13), mosaic forms, additional ring chromosome 13, isochromosomes.

Patients have severe anomalies of the structure: splitting of the soft and hard palate, cleft lips, underdevelopment or absence of eyes, malformed low-set ears, deformed bones of the hands and feet, numerous disorders of the internal organs, for example, congenital heart defects (defects of septa and large vessels ). Deep idiotic. The life expectancy of children is less than a year, more often 2-3 months. The population frequency is 1 in 7800.

2. Edwards syndrome (trisomy on chromosome 18). Described in 1960. Cytogenetically, in most cases it is represented by a whole trisomy 18 (gametic mutation of one of the parents, more often on the maternal side). In addition, mosaic forms are also encountered, and translocations are observed very rarely. The critical segment responsible for the formation of the main features of the syndrome is the 18q11 segment. Clinical differences between cytogenetic forms were not found. Patients have a narrow forehead and a wide protruding nape, very low deformed ears, underdevelopment of the lower jaw, wide and short fingers. From

internal malformations should be noted combined malformations of the cardiovascular system, incomplete bowel rotation, malformations of the kidneys, etc. Children with Edwards syndrome have low birth weight. There is a delay in psychomotor development, idiocy and imbecility. Life expectancy up to a year - 2-3 months. The population frequency is 1 in 6500.

Down syndrome (trisomy of chromosome 21). First described in 1866 by the English physician Down. The population frequency is 1 case per 600-700 newborns. The frequency of birth of children with this syndrome depends on the age of the mother and increases sharply after 35 years. Cytogenetic variants are very diverse, but about Fig. 15. S. Downa (6) top (8) bottom

95% of cases are represented by a simple trisomy of chromosome 21, as a result of nondisjunction of chromosomes in meiosis in the parents. The presence of polymorphic molecular genetic markers makes it possible to determine the specific parent and the stage of meiosis in which nondisjunction occurred. Despite intensive study of the syndrome, the causes of nondisjunction of chromosomes are still not clear. Etiologically important factors are intra- and extra-follicular over-ripening of the egg, a decrease in the number or absence of chiasmata in the first division of meiosis. Mosaic forms of the syndrome (2%), Robertsonian translocation variants (4%) were noted. About 50% of translocation forms are inherited from parents and 50% are mutations. de novo. The critical segment responsible for the formation of the main features of the syndrome is the 21q22 region.

Patients have shortened limbs, a small skull, a flat and wide nose bridge, narrow palpebral fissures with an oblique incision, an overhanging fold of the upper eyelid - epicanthus, excess skin on the neck, short limbs, a transverse four-finger palmar fold (monkey furrow). Of the defects of the internal organs, congenital malformations of the heart and gastrointestinal tract are often noted, which determine the life expectancy of patients. Characterized by mental retardation of moderate severity. Children with Down syndrome are often affectionate and affectionate, obedient and attentive. Their viability is reduced.

Clinical and cytogenetic characteristics of syndromes associated with anomalies of sex chromosomes.

1. Shereshevsky-Turner syndrome (X-chromosome monosomy). This is the only form of monosomy in humans that can be

found in live births. In addition to simple monosomy on the X chromosome, which is 50%, there are mosaic forms, deletions of the long and short arm of the X chromosome, iso-X chromosomes, and also ring X chromosomes. It is interesting to note that 45,X/46,XY mosaicism accounts for 2-5% of all patients with this syndrome and is characterized by a wide range of features: from typical Shereshevsky-Turner syndrome to a normal male phenotype.

The population frequency is 1 in 3000 newborns. Patients have small stature, barrel-shaped chest, broad shoulders, narrow pelvis, shortened lower limbs. A very characteristic feature is a short neck with folds of skin extending from the back of the head (the neck of the sphinx). They have low hair growth at the back of the head, hyperpigmentation of the skin, decreased vision and hearing. The inner corners of the eyes are higher than the outer ones. Congenital malformations of the heart and kidneys are common. Patients have underdevelopment of the ovaries. Barren. Intellectual development is within the normal range. There is some infantilism of emotions, instability of mood. Patients are quite viable.

2. Polysomy X syndrome ( Trisomy X). Forms 47,ХХХ, 48,ХХХХ and 49,ХХХХХ are revealed cytogenetically. With an increase in the number of X chromosomes, the degree of deviation from the norm increases. In women with tetra- and pentasomy X, deviations in mental development, anomalies of the skeleton and genital organs are described. Women with a karyotype of 47,XXX in full or mosaic form generally have normal physical and mental development, and intelligence - within the lower limit of normal. These women have a number of non-sharp deviations in physical development, ovarian dysfunction, premature menopause, but they can have offspring. The population frequency is 1 per 1000 newborn girls.

3. Klinefelter's syndrome. Described in 1942. The population frequency is 1 per 1000 boys. Cytogenetic variants of the syndrome may be different: 47.XXY: 48.XXYY; 48.XXXY; 49.XXXXY. Both complete and mosaic forms are noted. Patients of high stature with disproportionately long limbs. In childhood, they are distinguished by a fragile physique, and after 40 years they are obese. They develop an asthenic or eunuchoid body type: narrow shoulders, wide pelvis, female fat deposition, poorly developed

musculature, sparse facial hair. Patients have underdevelopment of the testes, lack of spermatogenesis, decreased sexual desire, impotence and infertility. Mental retardation usually develops. IQ below 80.

4. Syndrome of Y-chromosome polysemy (double-U or "extra Y chromosome"). The population frequency is 1 per 1000 boys. Cytogenetically marked complete and mosaic forms. Most individuals in physical and mental development do not differ from healthy ones. The gonads are developed normally, growth is usually high, there are some anomalies of the teeth and the skeletal system. Psychopathic traits are observed: instability of emotions, antisocial behavior, a tendency to aggression, homosexuality. Patients do not show significant mental retardation, and some patients generally have normal intelligence. They can have normal offspring in 50% of cases.

Clinical and genetic characteristics of syndromes associated with structural rearrangements of chromosomes.

Syndrome "cat's cry" (monosomy 5p). Described in 1963. The population frequency is 1 in 50,000. Cytogenetic variants vary from partial to complete deletion of the short arm of chromosome 5. The 5p15 segment is of great importance for the development of the main features of the syndrome. In addition to a simple deletion, circular chromosomes 5, mosaic forms, as well as translocations between the short arm of chromosome 5 (with the loss of a critical segment) and another autosome were noted.

Diagnostic signs of the disease are: microcephaly, an unusual cry or cry, reminiscent of a cat's meow (especially in the first weeks after birth); anti-Mongoloid incision of the eyes, strabismus, moon-shaped face, wide bridge of the nose. The auricles are low-set and deformed. There is a transverse palmar fold, anomalies in the structure of the hands and fingers. Mental retardation in the stage of imbecile. It should be noted that such signs as a moon-shaped face and a cat's cry are smoothed out with age, and microcephaly and strabismus come to light more clearly. Life expectancy depends on the severity of congenital malformations of the internal organs. Most patients die in the first years of life.

Clinical and cytogenetic characteristics of syndromes and malignant neoplasms associated with microstructural abnormalities of chromosomes.

Recently, clinical and cytogenetic studies have begun to rely on high-resolution methods of chromosomal analysis, which made it possible to confirm the assumption of the existence of microchromosomal mutations, the detection of which is on the verge of the capabilities of a light microscope.

Using standard cytogenetic methods, visual resolution of chromosomes with no more than 400 segments can be achieved, and using the methods of prometaphase analysis proposed by Younis in 1976, it is possible to obtain chromosomes with up to 550-850 segments. Minor disorders in the structure of chromosomes can be detected using these methods of chromosomal analysis not only among patients with CMHD, but also in some unknown mendelian syndromes, various malignant tumors. Most of the syndromes associated with chromosomal microabnormalities are rare - 1 case per 50,000-100,000 newborns.

Retinoblastoma. Patients with retinoblastoma - a malignant tumor of the retina, account for 0.6-0.8% of all patients with cancer. This is the first tumor for which a link with a chromosomal pathology has been established. Cytogenetically, this disease reveals a microdeletion of chromosome 13, segment 13q14. In addition to microdeletions, there are mosaic forms and translocation variants. Several cases of translocation of a segment of chromosome 13 to the X chromosome have been described.

There was no correlation between the size of the deleted fragment and phenotypic manifestations. The disease usually begins at the age of about 1.5 years and the first signs are the glow of the pupils, a sluggish reaction of the pupil to light, and then a decrease in vision up to blindness. Complications of retinoblastoma are retinal detachment, secondary glaucoma. In 1986, a tumor suppressor gene was discovered in the critical segment 13ql4 RBI, which was the first anti-oncogene discovered in humans.

Monogenic diseases manifested by chromosomal instability.

To date, new types of genome variability have been established that differ in frequency and mechanisms from the usual mutation process. One of the manifestations of genome instability at the cellular level is chromosomal instability. Chromosome instability is assessed by an increase in spontaneous and/or induced frequency of chromosome aberrations and sister chromatid exchanges (SChO). For the first time, an increased frequency of spontaneous chromosomal aberrations was shown in 1964 in patients with Fanconi anemia, and an increased frequency of CHO was found in Bloom's syndrome. In 1.968, it was found that xeroderma pigmentosa, a photodermatosis in which the frequency of UV-induced chromosomal aberrations is increased, is associated with a violation of the ability of cells to repair (repair) their DNA from damage caused by UV radiation.

At present, about one and a half dozen monogenic pathological signs associated with increased fragility of chromosomes are known. In these diseases, there are no specific sites of chromosomal damage, but the overall frequency of chromosome aberrations increases. The molecular mechanism of this phenomenon is most often associated with defects in individual genes encoding DNA repair enzymes. Therefore, most diseases accompanied by chromosomal instability are also called DNA repair diseases. Despite the fact that these diseases differ in their clinical manifestations, all of them are characterized by an increased tendency to malignant neoplasms, signs of premature aging, neurological disorders, immunodeficiency states, congenital malformations, skin manifestations, and mental retardation is often observed.

In addition to mutations in DNA repair genes, diseases with chromosomal instability may be based on defects in other genes that ensure genome stability. Recently, more and more data have been accumulating that, in addition to diseases manifested by instability of the chromosome structure, there are also monogenic defects that lead to diseases with instability in the number of chromosomes. Rare pathological conditions can be distinguished as such an independent group of monogenic diseases, indicating a non-random, hereditarily determined nature of non-disjunction of chromosomes in somatic cells during embryogenesis.

Cytogenetic examination of these patients in a small part of the cells (usually 5-20%) reveals somatic mosaicism on several chromosomes of the set at once, or one married couple may have several sibs with chromosomal mosaicism. It is assumed that such patients are "mitotic mutants" for recessive genes that control individual stages of the passage of mitosis. There is no doubt that most of these mutations are lethal, and surviving individuals have relatively mild forms of pathology of cell division. Despite the fact that the above diseases are caused by defects in individual genes, conducting a cytogenetic study in patients with suspected this pathology will help the doctor in the differential diagnosis of these conditions.

Diseases with instability of the structure of chromosomes:

Bloom syndrome. Described in 1954. The main diagnostic features are: low birth weight, growth retardation, narrow face with butterfly erythema, massive nose, immunodeficiency states, susceptibility to malignant neoplasms. Mental retardation is noted not in all cases. It is cytogenetically characterized by an increase in the number of sister chromatid exchanges (SChO) per cell up to 120-150, although normally their number does not exceed 6-8 exchanges per 1 cell. In addition, chromatid breaks are detected with a high frequency, as well as dicentrics, rings, and chromosome fragments. Patients have mutations in the DNA ligase 1 gene located on chromosome 19 - 19q13.3, but the Bloom syndrome gene is mapped in the 15q26.1 segment.

Anemia Fanconi . A disease with an autosomal recessive mode of inheritance. Described in 1927. The main diagnostic features: hypoplasia of the radius and thumb, growth and developmental delay, hyperpigmentation of the skin in the inguinal and axillary areas. In addition, bone marrow hypoplasia, a tendency to leukemia, and hypoplasia of the external genital organs are noted. It is cytogenetically characterized by multiple chromosomal aberrations - chromosome breaks and chromatid exchanges. This is a genetically heterogeneous disease, i.e. a clinically similar phenotype is due to mutations in different genes. There are at least 7 forms of this disease: A - the gene is localized in the 16q24.3 segment; B - localization of the gene is unknown; C - 9q22.3; D - Зр25.3; E - 6r22; F - 11r15; G (MIM 602956) - 9r13. The most common form is A - about 60% of patients.

Werner syndrome (syndrome of premature aging). A disease with an autosomal recessive mode of inheritance. Described in 1904. The main diagnostic features are: premature graying and baldness, atrophy of subcutaneous adipose tissue and muscle tissue, cataracts, early atherosclerosis, endocrine pathology (diabetes mellitus). Infertility, a high voice, a tendency to malignant neoplasms are characteristic. Patients die at the age of 30-40 years. Cytogenetically characterized by cell clones with different chromosomal translocations (mosaicism for different translocations). The disease gene is located in the 8p11-p12 segment.

Fragile X syndrome.

As a rule, chromosome breaks or chromatid gaps that occur with increased frequency in certain specific chromosomal segments (the so-called brittle sites or fragile sites of chromosomes) are not associated with any diseases. However, there is an exception to this rule. In 1969, in patients with a syndrome accompanied by mental retardation, the presence of a specific cytogenetic marker was found - in the distal part of the long arm of the X chromosome in the Xq27.3 segment, a gap or gap of chromatids is recorded in individual cells.

Later it was shown that the first clinical description of a family with a syndrome in which mental retardation is the leading clinical sign was described as early as 1943 by English doctors P. Martin and Y. Bell. Martin-Bell syndrome or fragile X syndrome is characterized by a fragile (fragil) X chromosome in the Xq27.3 segment, which is detected under special cell culture conditions in a folic acid-deficient medium.

The fragile site in this syndrome was designated FRAXA. The main diagnostic signs of the disease are: mental retardation, a broad face with features of acromegaly, large protruding ears, autism, hypermobility, poor concentration, speech defects, more pronounced in children. There are also connective tissue abnormalities with joint hyperextensibility and mitral valve defect. Only 60% of men with a fragile X chromosome have a relatively complete range of clinical signs, 10% of patients do not have facial anomalies, 10% have only mental retardation without other signs.

Fragile X syndrome is interesting for its unusual inheritance and high population frequency (1 in 1500-3000). An unusual inheritance is that only 80% of males carrying the mutant gene have signs of the disease, while the remaining 20% ​​are both clinically and cytogenetically normal, although after passing the mutation to their daughters they may have affected grandchildren. These men are called transmitters, i.e. transmitters of an unexpressed mutant gene that becomes expressed in subsequent generations.

In addition, there are two types of women - heterozygous carriers of the mutant gene:

a) daughters of male transmitters who do not have symptoms of the disease, in whom the fragile X chromosome is not detected;

b) granddaughters of normal male transmitters and sisters of affected males, who show clinical signs of the disease in 35% of cases.

Thus, a gene mutation in Martin-Bell syndrome exists in two forms that differ in their penetrance: the first form is a phenotypically non-manifested premutation that turns into a full mutation (second form) when passing through female meiosis. A clear dependence of the development of mental retardation on the position of the individual in the pedigree was found. At the same time, the phenomenon of anticipation is well traced - a more severe manifestation of the disease in subsequent generations.

The molecular mechanism of the mutation became clear in 1991, when the gene responsible for the development of this disease was characterized. The gene was named FMR1 (English - Fragile site Mental Retardation 1 - a fragile region of the chromosome associated with the development of type 1 mental retardation). It was found that the clinical manifestations and cytogenetic instability at the Xq27.3 locus are based on a multiple increase in the CGG simple trinucleotide repeat in the first exon of the FMR-1 gene.

In normal people, the number of these repeats on the X chromosome ranges from 5 to 52, while in sick people their number is 200 or more. Such a phenomenon of a sharp, spasmodic change in the number of CGG repeats in patients was called the expansion of the number of trinucleotide repeats: It was shown that the expansion of CGG repeats significantly depends on the sex of the offspring, it is noticeably increased when the mutation is transmitted from mother to son. It is important to note that the expansion of nucleotide repeats is a postzygotic event and occurs at very early stages of embryogenesis.

Unlike patients with other sex chromosomal aneuploidies, girls with Turner syndrome are often identified at birth or before puberty due to distinct phenotypic features. Turner's syndrome is much rarer than other sex chromosome aneuploidies. The incidence of the Turner syndrome phenotype is approximately 1 in 4,000 newborn girls, although some studies report significantly higher figures.

Most common chromosomal constitution at- 45,X (sometimes incorrectly written 45,X0), without a second sex chromosome. However, up to 50% of cases have other karyotypes. About a quarter of cases of Turner syndrome are mosaic karyotypes, in which only a fraction of the cells contain 45,X. The most common karyotypes and their approximate relative frequencies are as follows:

1) 45,X: 50%
2) 46,X,i(Xq): 15%
3) Mosaics 45,X/46,XX: 15%
4) Mosaics 45,X/46,X,i (Xq): about 5%
5) 45,X, other anomaly X: about 5%
6) Other mosaics 45,X/?: about 5%

Compound chromosomes clinically significant. For example, patients with i(Xq) are similar to women with classic 45,X, patients with an Xp deletion have short stature and congenital malformations, and those with an Xq deletion often have only gonadal dysfunction.

Typical anomalies in Turner syndrome include short stature, gonadal dysgenesis (the ovaries are usually striated as a result of abnormal ovaries formation), a characteristic unusual face, a wrinkled neck, low hair growth at the back of the head, a broad chest with widely spaced nipples, and a high incidence of renal and cardiovascular abnormalities.
At birth babies with this syndrome often have an important diagnostic feature - swelling of the back of the feet and hands.

Many patients find coarctation of the aorta, women with Turner syndrome have an increased risk of cardiovascular abnormalities. Lymphoedema can occur in the prenatal period, causing cystic hygroma of the fetus (detected by ultrasound) causing cervical folds visible after childbirth.

Turner syndrome should be suspected in any newborn girl with edema of the hands and feet or hypoplastic left heart or coarctation of the aorta. The possibility of this diagnosis should also be considered during adolescence in girls with primary or secondary amenorrhea, especially if they are short. Growth hormone therapy is indicated for all girls with Turner syndrome and allows you to add 6 to 12 cm in height.

It is generally believed that intelligence women with Turner syndrome will be normal, although approximately 10% of patients have significant developmental delay requiring special education. Even among those who have normal intelligence, however, there is often a deficiency in spatial perception, motor and fine motor skills.

As a result, non-verbal evaluation IQ significantly lower than verbal, and most patients need pedagogical support, especially in mathematics. Women with Turner syndrome are at high risk of poor social adaptation. Comparison of 45,X girls with maternal and paternal X chromosome ancestry showed significantly worse social skills with maternal X chromosome. Since the effect of parental origin may be explained by imprinting, this possibility is being investigated for X-linked genes that influence the phenotype.

High frequency karyotype 45,X already mentioned in spontaneous abortions. The anomaly is present presumably in 1-2% of all conceptions; survival to term is rare, and more than 99% of these pregnancies end spontaneously. The only X chromosome is maternal in about 70% of cases; in other words, the chromosomal error leading to the loss of the sex chromosome usually occurs in the father.

The basis for an unusually high frequency loss of an X or Y chromosome unknown. In addition, it is not clear why the 45,X karyotype, so often lethal in utero, is apparently fully compatible with life after birth. The lost genes responsible for the Turner syndrome phenotype must be located on both the X and Y chromosomes. It is believed that these genes are among the genes that avoid X-inactivation, in particular, those located on the short arm, including the pseudoautosomal region.

Sometimes in patients with low growth, gonadal dysgenesis and mental retardation reveal small circular X chromosomes. Since mental retardation is not typical for Turner syndrome, the presence of such a delay with other anomalies in patients with a 46,X,r(X) karyotype is associated with the fact that small circular X chromosomes lose the X inactivation center.

Inability to inactivate ring X chromosome leads to overexpression of genes that are normally subject to inactivation. Detection of the circular X chromosome in prenatal diagnosis can lead to great uncertainty, in which case a study of the XIST gene expression is indicated. Large rings containing an X-inactivation site and expressing the XIST gene lead to the development of the Turner syndrome phenotype; with small ring chromosomes without XIST gene expression, a more severe phenotype can be assumed.

Chromosomal diseases- ailments of a hereditary nature, which are caused by a change in the structure or number of chromosomes. This group of diseases also includes those caused by genomic mutations. Pathologies arise due to changes occurring in the germ cells of the parents.

The concept of chromosomal diseases

This is a large group of congenital ailments, which occupies one of the leading places in the list of human hereditary pathologies. Cytological studies of materials from early abortions show that human chromosomal diseases can manifest themselves even in embryos. That is, diseases develop even in the process of fertilization or in the early stages of crushing the zygote.

Types of chromosomal diseases

Experts are accustomed to dividing all ailments into three large types. The classification of chromosomal diseases depends on the disorders:

• ploidy;
• the number of chromosomes;
• chromosome structures.

The most common anomalies caused by a violation of ploidy are triplody and tetraplody. Such changes, as a rule, are recorded only in the material obtained as a result of abortions. Only isolated cases of the birth of children with such disorders are known, and they always interfered with normal life. Triploid is the result of fertilization of diploid eggs by haploid sperm or vice versa. Sometimes the anomaly is a consequence of the fertilization of one egg by two sperm.

Violation of the number of chromosomes

In most cases, chromosomal diseases caused by a violation of the number of chromosomes manifest themselves as a whole monosomy or trisomy. In the latter, all three nucleoprotein structures are homologues. At the first anomaly in the number of chromosomes, one of the two in the set remains normal. A whole monosomy occurs only on the X chromosome, since embryos with other sets die very early - even at the initial stages of intrauterine development.

Violation of the structure of chromosomes

Ailments that develop against the background of a violation of the structure of chromosomes are represented by a large group of syndromes with partial mono- or trisomy. They occur when there are structural changes in the parent germ cells. Such disturbances affect the processes of recombination. Because of this, in meiosis there is a loss or an excess of fragments of nucleoprotein structures. Partial chromosomal abnormalities can occur on any chromosome.

Causes of chromosomal diseases

Scientists have been working on this issue for a long time. As it turned out, chromosomal mutations cause disease. They lead to deviations in the structure and functions of nucleoprotein structures. It is necessary to know not only the causes of chromosomal diseases, but also the factors conducive to the manifestation of mutations. Meaning are:

• features involved in the anomaly;
• organism's genotype;
• type of anomaly;
• the size of the missing or excess genetic material (in case of structural disorders);
• the degree of cellular mosaicity of the body (only those cells that have deviations in structure or functions are taken into account).

Chromosomal diseases - list

Every year it is replenished with new names - ailments are constantly being investigated. Considering what chromosomal diseases are, the most famous today are:

1. Down Syndrome. Develops due to trisomy. That is, because there are three copies of the 21st chromosome in the cells, instead of two. As a rule, the "extra" structure is transferred to the newborn from the mother.
2. Klinefelter syndrome. This chromosomal disease does not appear immediately at birth, but only after puberty. As a result of this deviation, men receive from one to three X chromosomes and lose the ability to have children.
3. Myopia. is a genetic abnormality due to which the image is formed not where it should be - on the retina - but in front of it. The main cause of this problem is an increase in the length of the eyeball.
4. Daltonism. Colorblind people cannot distinguish one or more colors at once. The reason is in the “defective” X chromosome received from the mother. In the representatives of the stronger sex, this deviation is more common, because in men there is only one X-structure, and their cells cannot “fix the defect” - as happens in the case of female organisms.
5. Hemophilia. Chromosomal diseases can also be manifested by a violation of blood clotting.
6. Migraine. The disease, manifested by severe pain in the head, is also inherited.
7. Cystic fibrosis. This disease is characterized by a violation of the work of the glands of external secretion. People with this diagnosis suffer from excessive sweating, copious mucus secretion that accumulates in the body and interferes with the correct functioning of the lungs.

Methods for diagnosing chromosomal diseases

Genetic consultations, as a rule, turn to such methods for help:

1. Genealogical. It consists in the collection and analysis of data on the patient's pedigree. This method allows you to understand whether the disease is actually hereditary and, if so, to determine the type of inheritance.
2. Antenatal diagnosis. Determines the hereditary disorders of the fetus, which is in the womb for a period of 14-16 weeks of pregnancy. If autosomal abnormalities are detected in the amniotic fluid, it can be done.
3. Cytogenetic. Used to identify syndromes and abnormalities.
4. Biochemical. Clarifies diseases and helps identify mutated genes.

Treatment of chromosomal diseases

Therapy does not always help get rid of the disease, but it can slow down its course. Chromosomal abnormalities of the fetus are treated by the following methods:

1. Diet therapy. Involves the addition or exclusion of certain substances from the diet.
2. Medical therapy. It is used to influence the mechanisms of enzyme synthesis.
3. Surgery. Helps to cope with various bone defects and deformities.
4. replacement therapy. Its essence is to compensate for those substances that are not synthesized independently in the body.

Frequency of chromosomal diseases

Very often, human chromosomal abnormalities are found in materials obtained as a result of spontaneous abortions made in the first trimester. The overall frequency of disorders in the population is actually not so high and is about 1%. Children with genetic abnormalities can be born to healthy parents. Newborn girls and boys, as medical practice shows, are affected by chromosomal diseases with the same frequency.

Chromosomal diseases or syndromes are a group of congenital pathological conditions manifested by multiple malformations, differing in their clinical picture, often accompanied by severe disorders of mental and somatic development. The main defect is various degrees of intellectual insufficiency, which can be complicated by visual, hearing, and musculoskeletal disorders, more pronounced than intellectual defects, speech, emotional and behavioral disorders.

Diagnostic signs of chromosomal syndromes can be divided into three groups:

non-specific, i.e. such as severe mental retardation, combined with dysplasia, congenital malformations and craniofacial anomalies;

signs characteristic of individual syndromes;

pathognomonic for a particular syndrome, for example, specific crying in the "cat's cry" syndrome.

Chromosomal diseases do not follow the Mendeleian patterns of disease transmission to offspring and in most cases are detected sporadically, as a result of a mutation in the germ cell of one of the parents.

Chromosomal diseases can be inherited if the mutation is present in all cells of the parent organism.

The mechanisms underlying genomic mutations include:

non-disjunction - chromosomes that were supposed to separate during cell division remain connected and belong to the same pole;

"anaphase lag" - the loss of a single chromosome (monosomy) can occur during anaphase, when one chromosome can lag behind the rest;

polyploidization - in each cell the genome is presented more than twice.

Factors that increase the risk of having children with chromosomal diseases

The causes of chromosomal diseases have not been sufficiently studied so far. There are experimental data on the influence on the mutation process of such factors as: the action of ionizing radiation, chemicals, viruses. Other reasons for non-disjunction of chromosomes can be: seasonality, the age of the father and mother, the order of birth of children, medication during pregnancy, hormonal disorders, alcoholism, etc. The genetic determination of non-disjunction of chromosomes is not excluded to a certain extent. Let us repeat, however, that the reasons for the formation of genomic and chromosomal mutations at the early stages of embryonic development have not yet been fully elucidated.

Maternal age can be attributed to biological factors that increase the risk of having children with chromosomal abnormalities. The risk of having a sick child increases especially sharply after 35 years. This is characteristic of any chromosomal disease, but is most clearly observed for Down's disease.

In medical genetic planning of pregnancy, two factors are of particular importance - the presence of autosomal aneuploidy in a child and the age of the mother over 35 years.

Karyotypic risk factors in married couples include: aneuploidy (often in mosaic form), Robertsonian translocations (fusion of two telocentric chromosomes in the area of ​​division), ring chromosomes, inversions. The degree of increased risk depends on the type of chromosomal disorder.

Down syndrome (trisomy of 21 pairs of chromosomes)

Cause: Non-disjunction of 21 pairs of autosomes, translocation of 21 autosomes to the autosome of group D or G. 94% have a karyotype of 47 chromosomes. The frequency of manifestation of the syndrome increases with the age of the mother.

Clinic: Signs that allow diagnosing the disease, in typical cases, are detected at the earliest stages of a child's life. The small stature of the child, a small round head with a sloping nape, a peculiar face - poor facial expressions, an oblique cut of the eyes with a crease at the inner corner, a nose with a wide flat bridge of the nose, small deformed auricles. The mouth is usually half open, the tongue is thick, clumsy, the lower jaw sometimes protrudes forward. Dry eczema is often noted on the cheeks. Shortening of the limbs is found, especially in the distal sections. The hand is flat, the fingers are wide, short. They lag behind in physical development, but not sharply, but neuropsychic development is slow (speech is poorly developed). With age, a number of new features of the disease are revealed. The voice coarsens, myopia, strabismus, conjunctivitis, abnormal growth of teeth, caries are noted. The immune system is poorly developed, infectious diseases are extremely difficult and 15 times more common than in other children. There is acute leukemia.

Pathogenesis: Pathologies of internal organs, cardiovascular defects.

Diagnostics: Clinical examination confirmed by cytogenetic analysis of the karyotype.

Treatment: Complex therapy, including the correct organization of the regimen, rationally constructed medical and pedagogical work, physiotherapy exercises, massage, drug treatment.

Turner-Shershevsky Syndrome (CS)

Cause: Nondisjunction of sex chromosomes, absence of one X chromosome, karyotype - 45 chromosomes.

Clinic : Short stature, disproportionate body structure, full short neck with pterygoid skin folds, wide chest, X-shaped curvature of the knees. The ears are demorphed, set low. Abnormal growth of teeth is noted. Sexual infantilism. Decreased mental development.

Pathogenesis: During puberty, underdevelopment of the genital organs and secondary sexual characteristics, damage to the vascular system, anomalies of the urinary system, decreased visual acuity, hearing.

Diagnostics : In newborns, it is difficult to establish. With age, the diagnosis is based on the clinical picture and the determination of the pathology of the karyotype and sex chromatin.

Treatment: Symptomatic, aimed at increasing growth. Anabolic hormones are used to increase growth. From the age of 13-15, treatment with estrogenic drugs begins. Complete recovery is not observed, but therapeutic measures can improve the condition

Klinefelter syndrome (XXY; XYY; XYYYY; XXXY)

Cause: Nondisjunction of sex chromosomes, as a result of which the number of X or Y chromosomes in the cell increases, the karyotype is 47 (XXY), 48 or more chromosomes.

Clinic: High growth, lack of bald patches on the forehead, poor beard growth, gynecomastia, osteochondrosis, infertility, underdeveloped muscles, anomalies of the teeth and skeletal system. Patients may demonstrate reduced intelligence. With an increase in X chromosomes, mental retardation increases to complete idiocy, with an increase in Y chromosomes - aggressiveness. Patients with a deeper degree of intellectual defect may show a number of psychopathological signs: they are suspicious, prone to alcoholism, capable of committing various offenses.

Pathogenesis: In the pubertal period, underdevelopment of primary sexual characteristics is found.

Diagnostics: Based on clinical data, as well as on the determination of the pathological karyotype by the cytogenetic method, which is confirmed by the study of sex chromatin in cells.

Treatment: Therapy with male sex hormones to increase potency. Psychotherapy.

Wolf-Hirshhorn syndrome

Cause: In 80% of newborns suffering from it, the cytological basis of this syndrome is the division of the short arm of the 4th chromosome. The size of the deletion ranges from small terminal to occupying about half of the distal part of the short arm. It is noted that most of the deletion occurs again, about 13% occurs as a result of translocations in the parents. Less commonly, in the genome of patients, in addition to translocation, there are also ring chromosomes. Along with divisions of chromosomes, pathology in newborns can be caused by inversions, duplications, isochromosomes.

Clinic: Newborns have a small weight with a normal duration of pregnancy. Microcephaly, coracoid nose, epicanthus, anti-Mongoloid incision of the eyes (omission of the outer corners of the eye fissures), abnormal auricles, cleft lip and palate, small mouth, deformity of the feet, etc. are also noted. Children with Wolff-Hirschhorn syndrome are not viable, usually die in under the age of one year.

Pathogenesis: The disease is characterized by numerous congenital malformations, mental retardation and psychomotor development.

Diagnostics: According to the clinical picture.

Treatment: Does not exist.

trisomy syndrome (XXX)

Cause: Nondisjunction of sex chromosomes as a result of disruption of the mitotic spindle during meiosis, karyotype - 47 chromosomes.

Clinic: Vesical non-disjunction of the placenta; the newborn has a small, wide posterior fontanel, underdeveloped occipital and parietal bones of the skull. Lag in development for 6-7 months. Deformed auricles are located low. Syndactyly of the fingers, cleft lip and palate, hydrocephalus. Many women are normally developed, intelligence is below average. The frequency of development of schizophrenia-like psychoses increases second.

Pathogenesis: Malformations of internal organs.

Diagnostics: According to the clinical picture and cytogenetic definition of the pathology of the karyotype and sex chromatin.

Treatment: Symptomatic.

Edwards syndrome (trisomy of chromosome 18)

Cause: Nondisjunction of autosomes at the stage of gametes (sometimes zygotes). Extra chromosome in the 18th pair. Karyotype 47, E18+. The dependence of the frequency of birth of sick children on the age of the parents is expressed.

Clinic: Prenatal underdevelopment, weak fetal activity, structural disorders of the face (short palpebral fissures, small upper jaw) and the musculoskeletal system are almost constant. The auricles are deformed and in the vast majority of cases are located low. The sternum is short, the ossification nuclei are located incorrectly and in smaller numbers. Spinal hernias and cleft lips.

Pathogenesis: The most permanent defects of the heart and large vessels. Developmental disorders of the brain, mainly hypoplasia of the cerebellum and corpus callosum. Of the defects of the eyes, microanaphtholmia is most often detected. Congenital absence of the thyroid gland and adrenal glands.

Diagnostics: Clinical examination, dermatoglyphics,

cytogenetic examination.

Treatment: Absent, 90% of children die in the first year of life. Surviving children die from infectious diseases, more often from pneumonia.

Patau syndrome (trisomy but 13 autosomes)

Cause: Nondisjunction of autosomes of the 13th pair in gametogenesis in one of the parents. Karyotype - 47, D13+.

Clinic: Anomalies of the skull and face, the circumference of the skull is usually reduced, in some cases there is a pronounced trigonocephaly. Moderate microcephaly is combined with a relatively low and sloping forehead, narrow palpebral fissures, a sunken forearm with a wide base of the nose, and low-lying and deformed auricles. The distance between the palpebral fissures is often reduced. The scalp has oval or round shaped scalp defects. Often - cleft lip and cleft palate. Anomalies of the musculoskeletal system, polydactyly.

Pathogenesis: Mortality during the first year of life (90%). The main cause of death in children are severe, incompatible with life malformations: defects in the cardiovascular and genitourinary systems, anomalies of the large intestine, umbilical hernia, disorders of the structure of the eyeballs, constant microanophthalmia, retinal dysplasia, cataracts. Congenital heart defects occur in 80% of children.

Diagnostics: Based on clinical, cytogenetic studies.

Syndrome "cat's cry"

Cause: Deletion of the short arm of chromosome 5. Karyotype 46, 5p-.

Clinic: Pathological structure of the vocal cords - narrowing, softness of the cartilage, swelling and unusual folding of the mucosa, meowing of a cat. Underdevelopment of speech. Microcephaly. Moon-shaped face, Mongoloid incision of the eyes, strabismus, cataracts, optic nerve atrophy, flat nasal bridge, high palate, deformed auricles. Clubfoot. Delayed mental and physical development. Life expectancy is significantly reduced, with only about 14% of patients surviving the age of 10 years.

Pathogenesis: Heart disease.

Diagnostics: Clinical examination with the identification of the most constant sign of the syndrome - "cat's cry", dermatoglyphics and cytogenetic detection of karyotype pathology.

Treatment: Is absent.

Orbeli syndrome

Cause : Divisions of the long arm of the autosome 13.

Clinic: The forehead passes into the nose without forming a nasal notch. Large distance between eyes. Wide back of the nose, high palate, low-lying dysplastic auricles, malformations of the eyes (strabismus, cataracts). Defects of the musculoskeletal system - nonspecific anomalies (clubfoot, dislocation of the hip joints). growth retardation and psychomotor development; characterized by profound oligophrenia. Patients with a detailed clinical picture of the syndrome die in the first year of life.

Pathogenesis: Abnormal development of almost all organs and systems; microcephaly; congenital heart defects and anomalies of the rectum.

Diagnostics:

Treatment: Is absent.

Maurice syndrome

Cause: A gene mutation that disrupts the formation of a normal receptor protein makes target tissues resistant to the hormone that directs their development in the male pattern. Without using this opportunity at a certain stage of ontogenesis, the organism develops according to the female type.

Clinic: An individual with the XY karyotype appears, but outwardly it is more similar to a woman. Such subjects are not able to have offspring, since their sex glands (testes) are underdeveloped, and their excretory ducts are often formed according to the female type (underdeveloped uterus, vagina). Secondary sexual characteristics are also characteristic of the female.

Pathogenesis: Underdeveloped genitals.

Diagnostics: Cytogenetic, clinical examination.

Treatment: hormone therapy.

Numerical disorders in the system of sex chromosomes (monosomy and trisomy) do not cause such severe consequences as autosomal anomalies. Pronounced changes in the phenotype are few or absent (for example, in women with a 47.XXX karyotype). In the preliminary diagnosis of diseases caused by abnormalities of the sex chromosomes, the anamnesis is of primary importance: delayed sexual development, impaired formation of secondary sexual characteristics, infertility, spontaneous abortions. Express methods of cytogenetic analysis (for example, the determination of sex chromatin in scraping from the buccal mucosa) do not always give reliable results. Therefore, if a sex chromosome abnormality is suspected, a detailed cytogenetic study of a large number of cells is required. One of the main objectives of such a study is the exclusion of mosaicism in gonadal dysgenesis. The presence in a patient with mosaicism of a clone of cells carrying the Y chromosome indicates an increased risk of gonadoblastoma. In cases where the probability of anomaly of sex chromosomes is high, but an anomaly is not found in lymphocytes, cells of other tissues (usually skin fibroblasts) should be examined.

1. Turner syndrome is a clinical manifestation of an anomaly of one of the X chromosomes in women. Turner syndrome in 60% of cases is due to monosomy of the X chromosome (45,X karyotype), in 20% of cases - mosaicism (for example, 45,X / 46,XX) and in 20% of cases - an aberration of one of the X chromosomes (for example, 46,X). The prevalence of Turner syndrome due to complete monosomy of the X chromosome (45,X) among children born alive is 1:5000 (in girls 1:2500). Fetuses with a 45,X karyotype are spontaneously aborted in 98% of cases. The syndrome is characterized by multiple malformations of the skeleton and internal organs. The most important phenotypic features: short stature and dysgenesis or complete absence of gonads (in place of the ovaries, undifferentiated connective tissue strands are found that do not contain germ cells and follicles). Other signs: short neck with pterygoid skin folds, low hairline at the back of the head, barrel-shaped chest, facial proportions, O-shaped curvature of the arms (deformity of the elbow joints), X-shaped curvature of the legs.

a. Cytogenetic variants of the syndrome. Patients with a 45,X karyotype usually lack a paternal X chromosome; maternal age is not a risk factor. The 45,X karyotype in most cases is due to nondisjunction of the sex chromosomes in the 1st division of meiosis (as a result, only one X chromosome enters the zygote), less often due to mitosis disorders in the early stages of zygote cleavage. In patients with mosaicism, there are cell clones containing two X chromosomes (45,X / 46,XX), X and Y chromosomes (45,X / 46,XY) or clones with X chromosome polysomy (for example, 45, X/47,XXX). Translocations between the X chromosome and autosomes are sometimes observed. Translocations and the presence of additional cell lines in patients with mosaicism strongly influence the formation of the phenotype. If there is a clone of cells carrying the Y-chromosome, then in the rudiments of the gonads on one or both sides, hormonally active testicular tissue may be present; there are external genital organs of an intermediate type (from a hypertrophied clitoris to an almost normal penis). Possible aberrations of the X chromosome in Turner syndrome: long arm isochromosome, in rare cases short arm isochromosome; terminal deletion of the long arm or deletion of the entire long arm (Xq -), terminal deletion of the short arm or deletion of the entire short arm (Xp -); terminal rearrangement of the X chromosome; ring X chromosome. If the aberrant X chromosome is inactivated, the aberration may not show up in the phenotype at all or show up incompletely. In the latter case, the aberration is partly compensated by the presence of a normal X chromosome (gene dose effect). Aberrations of the X chromosome are often combined with mosaicism, i.e., with the presence of a 45,X cell clone [for example, 45,X/46X,i(Xp)]. In a translocation between the X chromosome and an autosome, the karyotype may be balanced or unbalanced. Even if the translocation is balanced, the frequency of malformations or mental retardation is increased. The normal X chromosome is usually inactivated in autosomal X translocation. In rare cases, patients with Turner syndrome (including patients with mosaicism with a 45,X cell clone) have an aberrant Y chromosome. The recurrent risk of having a child with Turner syndrome is low unless one or both parents have an inherited autosomal X translocation or when the mother carries a 45,X cell clone.

b. The characteristic signs of Turner's syndrome in newborns are lymphatic edema of the extremities and heart defects (occur in approximately 20% of patients). Defects in 75% of cases are represented by defects of the interventricular septum or coarctation of the aorta. Any girl or woman with severe stunting should be evaluated, even if there are no other signs of the syndrome. Other indications for examination: delayed puberty, isolated delayed menarche, dysmenorrhea, infertility, repeated spontaneous abortions (3 or more), premature menopause. Important information is provided by the determination of the level of gonadotropic hormones (especially in girls of younger and prepubertal age). The final diagnosis of Turner's syndrome should be based on cytogenetic analysis. At least 50 cells should be viewed.

in. Management of patients with Turner's syndrome. The primary task is a detailed examination of patients, especially young girls. The purpose of the examination is to identify heart defects, aortic dissection, anomalies of the gastrointestinal tract and kidneys, and hearing impairment. Surgery may be required. Chronic lymphocytic thyroiditis, chronic inflammatory bowel disease, and hypertension are common in older girls and women; these diseases require long-term conservative treatment. Treatment somatropin(sometimes in combination with anabolic steroids) accelerates growth in childhood and increases the growth of adult patients. Treatment with somatropin can be started from 2 years of age (but only in cases where the girl's height is less than the 5th percentile). Replacement therapy low doses estrogen they begin, as a rule, after ossification of the epiphyses (from the age of 14). If the patient is seriously experiencing the absence of pubertal changes, estrogens are prescribed earlier. Even with hormone treatment, secondary sexual characteristics are often not fully formed. Women with Turner syndrome are usually infertile, but in rare cases spontaneous ovulation occurs and pregnancy may occur. In some patients, menstruation appears and the level of gonadotropic hormones normalizes in the absence of hormone replacement therapy. The risk of malformations in the offspring of patients is increased. Women with Turner syndrome are warned about the risk of spontaneous abortion and premature menopause, and if pregnancy is suspected, prenatal diagnosis is offered.

2. Trisomy on the X chromosome (47,XXX) occurs in newborn girls with a frequency of 1:1000; rarely diagnosed in early childhood; adult patients usually have a normal female phenotype.

a. A few prospective studies have shown that women with a 47.XXX karyotype most often have: tall height; mental retardation (usually mild); late development of speech; epilepsy; dysmenorrhea; infertility. The risk of having a baby with trisomy X is increased in older mothers. For fertile women with a 47.XXX karyotype, the risk of having a child with the same karyotype is low. There appears to be a protective mechanism that prevents the formation or survival of aneuploid gametes or zygotes.

b. With polysomy of the X chromosome with more than three X chromosomes (for example, 48,XXXX, 49,XXXXX) there is a high probability of severe mental retardation, facial proportions, skeletal or internal malformations. Syndromes of this kind are rare and usually sporadic.

3. Klinefelter's syndrome is a clinical manifestation of X chromosome polysomy in males (prevalence is about 1:500). The most common karyotype 47,XXY(classic variant of the syndrome), but there are also rarer karyotypes: 48,XXXY; 49.XXXXY; 48,XXYY; 49,XXXYY. The presence of at least two X chromosomes and one Y chromosome in the karyotype is the most common cause primary hypogonadism in men.

a. Approximately 10% of patients with Klinefelter's syndrome have mosaicism 46,XY/47,XXY. Since a clone of cells with a normal karyotype is involved in the formation of the phenotype, patients with 46,XY/47,XXY mosaicism may have normally developed gonads and be fertile. The extra X chromosome is inherited from the mother in 60% of cases, especially during late pregnancy. The risk of inheriting the paternal X chromosome does not depend on the age of the father.

b. Klinefelter's syndrome is characterized by phenotypic polymorphism. The most common features are: tall stature, disproportionately long legs, eunuchoid build, small testicles (long axis< 2 см). Производные вольфова протока формируются нормально. В детском возрасте нарушения развития яичек незаметны и могут не выявляться даже при биопсии. Эти нарушения обнаруживают в пубертатном периоде и позднее. В типичных случаях при биопсии яичка у взрослых находят гиалиноз извитых семенных канальцев, гиперплазию клеток Лейдига, уменьшение численности или отсутствие клеток Сертоли; сперматогенез отсутствует. Больные, как правило, бесплодны (даже если есть признаки сперматогенеза). Формирование вторичных половых признаков обычно нарушено: оволосение лица и подмышечных впадин скудное или отсутствует; наблюдается гинекомастия; отложение жира и рост волос на лобке по женскому типу. Как правило, психическое развитие задерживается, но у взрослых нарушения интеллекта незначительны. Нередко встречаются нарушения поведения, эпилептическая активность на ЭЭГ , эпилептические припадки. Сопутствующие заболевания: рак молочной железы, сахарный диабет, болезни щитовидной железы, ХОЗЛ .

in. Methods for the treatment of infertility in Klinefelter's syndrome have not yet been developed. Testosterone replacement therapy usually begins at 11-14 years of age; with androgen deficiency, it significantly accelerates the formation of secondary sexual characteristics. In adult patients, libido increases during testosterone treatment. Gynecomastia may require surgery. Psychotherapy contributes to the social adaptation of patients with Klinefelter's syndrome and patients with other sex chromosome anomalies.

4. Karyotype 47,XYY. This variant of aneuploidy is the least studied, attracts the attention of doctors and excites the interest of the general public.

a. This chromosomal anomaly occurs in men with a frequency of 1:800 and rarely manifests itself in childhood. Adult carriers of the 47,XYY karyotype in most cases have a normal male phenotype. The extra (paternal) Y-chromosome appears most often as a result of non-disjunction of chromatids in the 2nd division of meiosis. Father's age is not a risk factor.

b. Carriers of the karyotype 47,XYY are characterized by high growth; pubertal growth acceleration occurs earlier and lasts longer than usual. Often there are minor malformations; the association of the 47,XYY karyotype with major malformations has not been proven. Occasionally, ECG changes, nodular or abscessed acne, and varicose veins are observed, but an increased risk of these disorders in individuals with a 47,XYY karyotype has not been confirmed. Mental development is within the normal range, but speech development is delayed. Often adolescents and men with a 47,XYY karyotype are very aggressive, prone to criminal acts and do not adapt well to life in society. In most, the development and function of the gonads is normal, but cases of underdevelopment of the testicles, infertility or reduced fertility are known.

in. Treatment is not required. If a 47,XYY karyotype is found during prenatal testing or in a prepubertal child, parents should be counseled truthfully and in detail. An adult male who has a 47,XYY karyotype for the first time needs psychological support; genetic counseling may be required. Married couples in which the man has a 47,XYY karyotype are recommended to have prenatal diagnosis, although in such families the children usually have a normal karyotype.