Chromosomal diseases
Chromosomal diseases are syndromes, the development of which is caused by changes in the number or structure of chromosomes. The incidence of chromosomal diseases among newborns is about 1%.The gross anomalies of chromosomes are incompatible with life and are a frequent cause of spontaneous abortions, miscarriages and stillbirths. Spontaneous abortions revealed about 20% of embryos with an abnormal set of chromosomes. Isolate groups of chromosomal diseases, characterized by changes in sex chromosomes and non-sexual chromosomes - autosomes. The anomalies of sex chromosomes include Shereshevsky-Turner syndrome( 45, X0), Klinefelter syndrome( 47, XXU), X chromosome trisomy syndrome( 47, XXX), and also more rare variants.
The appearance of anomalies of sex chromosomes is due to their non-divergence in meiosis or in divisions in the early development of the zygote. As a result of non-discrepancy of sex chromosomes, one of the spermatozoa can have 22 autosomes and both sex XY chromosomes( male and female), the other spermatozoa have only 22 autosomes. Also, when the sex chromosomes are non-divergent, the formation of oocytes containing 22 autosomes and two female X-chromosomes or only 22 autosomes is possible. Theoretically, the Shereshevsky-Turner syndrome with a set of sex chromosomes XO can occur when a normal egg is fertilized with a sperm that does not contain a sex chromosome, or when a female egg without a sex chromosome is fertilized with a sperm bearing a female X chromosome in its kit. When fertilizing an ovule with two X chromosomes, a spermatozoid with an X chromosome will form a trisomy X syndrome. The onset of Klinefelter's syndrome occurs when the ovum is fertilized with an X-chromosome with a sperm containing the X and Y chromosome.
More complex anomalies of sex chromosomes may be associated with the fertilization of an ovule with two X chromosomes by a sperm carrying X and Y chromosomes, etc. The cause of complex anomalies is also the non-divergence of the sex chromosomes both during the formation of the sex cells and onearly stages of the division of the zygote. The overall frequency of anomalies in sex chromosomes in stillborn children is 2.7%, which is 25 times higher than among newborns.
ANOMALIES OF SEXUAL CHROMOSOME
Syndrome Shereshevsky-Turner( monosomy X)
For the first time a woman with complete absence of menstruation, insufficient development of secondary sexual characters and low growth was described by NA Shereshevsky in 1925. In 1938 XX Turner published data on 7women with low growth, delayed sexual development, lack of menstrual function, infertility and pterygopal folds on the neck.
The occurrence rate of the Shereshevsky-Turner syndrome is 1 case per 3,000 newborn female children. This is significantly less than the theoretically expected results, which is explained by the high frequency of spontaneous abortions. At the same time, many embryos die at the initial stages of pregnancy.
Newborn girls with Shereshevsky-Turner syndrome have marked swelling, located mainly on the back of the hands and feet. Such swelling, as a rule, disappear within a few months after birth. There is excess and increased mobility of the skin on the neck. With age, the child's lag in growth becomes clearly noticeable. The small growth of these girls is combined with normal body proportions, although the child's appetite can be increased. Half of the girls can see a short neck with a pterygoid fold of the skin. Outwardly, the face of these children looks mature enough, and the features of the constitution do not correspond to the expected age( infantile physique).On the skin there are pigmented spots, white spots( vitiligo), peripheral nerves tumors( neurofibromas), vascular tumors( hemangiomas) may appear.
Some girls with Shereshevsky-Turner syndrome may experience various anomalies of the skeleton: a barrel-shaped or less often flat chest, fusion of the vertebrae with each other, crevices in the vertebrae, curvature of the feet inside( relative to the midline of the body), short bones of the wrist and tarsus. It is often possible to notice various deformities of the teeth. On the part of internal organs, a characteristic manifestation of the syndrome are all kinds of congenital anomalies of the cardiovascular system. The most characteristic feature is coarctation of the aorta. Also, quite often in girls with a thorough examination in the hospital, they identify stenoses of the aortic and pulmonary artery mouth, defect of the interventricular septum. Quite often, there is an increase in blood pressure, which can be due to both coarctation of the aorta, and concomitant disorders of kidney development. Individual children may experience bleeding from the gastrointestinal tract. By the period of puberty there are signs of lag in sexual development( sexual infantilism).In this case, the mammary glands are absent or are represented by fat tissue, the nipples are widely spaced and underdeveloped, the hair on the pubis and under the arms is rather meager. External genitalia are underdeveloped. The vagina is long and narrow. The uterus is reduced in size. An inherent feature of the Shereshevsky-Turner syndrome is the complete absence of menstruation, but some girls may have rare meager menstruation.
Children lag behind in mental development. The interest to the opposite sex is reduced. Logical thinking is limited. Girls are not critical of the defect they have. They are usually complacent, hardworking, helpful. The peculiarity of the Shereshevsky-Turner syndrome is the complete manifestation in children of hereditary diseases transmitted through the X-linked type. Such diseases include hemophilia, myopathy, color blindness.
Radiographic examination of the bone system reveals a delay in ossification even in persons of mature age. There are deformations of the spine - kyphosis, scoliosis, shortening of vertebral bodies, osteoporosis. With special methods of examination, ovarian underdevelopment is detected. In biochemical studies in Moche there is an increase in the number of hormones that appear in the period of puberty. The content of female sex hormones in the urine is reduced.
Study of chromosomal recruitment in girls with Shereshevsky-Turner syndrome reveals 45 chromosomes: 22 pairs of autosomes and one X chromosome. Another characteristic feature is the absence of sexual chromatin in the nuclei of skin cells. Sex chromatin( Barra's body) is present in most of the somatic cell nuclei of normal girls.
It is believed that the Shereshevsky-Turner syndrome is more likely due to the non-divergence of the sex chromosomes in the process of sperm formation than the oocytes.
Some of the girls with Shereshevsky-Turner syndrome, who do not detect sexual chromatin in skin cells, can identify a male set of chromosomes 46, XY.Pathological changes in this case are explained by the lack of activity of the male Y chromosome, which externally manifests itself as a set of sex chromosomes of XO.This condition is observed underdevelopment of the sexual glands in girls with normal growth with varying degrees of puberty. With the male Y-chromosome retained to some extent, the patients look outwardly like boys, have dwarf growth with individual somatic changes, shortening of the neck, small undescended testicles. The intellect of such boys is reduced. These are people with the so-called male Shereshevsky-Turner syndrome. In rare cases, in people with a lack of sexual chromatin in skin cells( chromatinous faces), a mosaic chromosome set XO / XY is found, that is, in one somatic cells there is one sex female X chromosome, in others X and Y chromosomes. This syndrome is found in girls with maldevelopment of the gonads, in boys with non-admission testicles, as well as in children with hermaphroditism. A special feature of this type of syndrome is the high frequency of development of tumors of the sex glands.
All variants of the Shereshevsky-Turner syndrome with chromosomal sets XO, 46, XY, XO / XY described above are chromatin-negative, ie, in all these cases in the cells of the body( somatic cells), in particular in the skin cells, do not reveal the sex chromatin. In addition, chromatin-positive conditions have been described( sex chromatin is determined in skin cells), whose frequency is approximately 4 times lower than the former. In some individuals, as a result of a genetic examination, two female X chromosomes were identified, but one of them was morphologically altered: the loss of a part of the chromosome, the annular X chromosome. Often there is a mosaic of XO / XX, when in some cells there are two X-chromosomes, in others - one X-chromosome. Symptoms of the disease in these people are less pronounced than with CHO syndrome: edema at birth and pterygoid cervical fold are noted in some cases, growth can remain normal, more often spontaneous menstruation occurs. Ovaries can be unchanged. Taurus Barra( sexual chromatin) with mosaicism are detected, but in a smaller amount compared to healthy girls. Mosaicism on the sex chromosomes can be combined with the loss of part of the X chromosome.
Sometimes there are individuals with a set of sex chromosomes XO / XX / XXX.Externally, this kind of mosaicism manifests itself in various variants of the Shereshevsky-Turner syndrome. When mosaic XO / XX / XXX in the nuclei of the skin cells of the Barra body there are no or there are one or two bodies. When mosaic XO / XXX, the sex chromatin is absent completely or is contained in a minimal amount. Manifestations of this condition are swelling of the lymph nodes, a pterygoid fold of the skin on the neck, changes from the internal organs are detected much less often. The sex glands are usually underdeveloped.
Another variety of mosaicism in the chromatin-positive syndrome of Shereshevsky-Turner is characterized by a ring female X-chromosome. Outwardly, these girls resemble those with a chromosome XO / XX set. Syndrome Shereshevsky-Turner, in which the sex chromatin is determined in the nuclei of cells, can be combined with small sex chromosomes, of which one normal X chromosome is combined with another small sex chromosome. In girls, underdevelopment of the sex glands is revealed, and developmental lag. When studying the chromosome set, various combinations and anomalies of the sex chromosomes are revealed.
All individuals with the Shereshevsky-Turner syndrome exhibit characteristic changes in the skin patterns of the fingers and palms, which are determined by the method of fingerprinting.
To confirm the disease, it is necessary to study the sex chromatin and chromosome set in a specialized hospital. Indications for conducting such a study in boys are mild secondary secondary sexual characteristics, undescended and underdeveloped testicles, low growth and decreased intelligence.
For the treatment of this syndrome hormones are used, and the use of female sex hormones is advisable after cessation of growth. In the case of earlier use of female hormones, premature growth arrest is possible. The course of hormonal treatment is 6-12 months. With effective treatment, the mammary glands are enlarged, menstruation appears, after which the dose of hormones is reduced.
The syndrome of Klinefelter
The syndrome was first described in 1942 by H. V. Klinefelter, who noted the characteristic signs of the disease: hypoplasia of the testicles, an increase in mammary glands in men, insufficient development of the external genital organs and increased urinary release of follicle-stimulating hormone. In 1956, a part of people with Klinefelter's syndrome discovered sexual chromatin, after which Barr proposed the division of the syndrome into chromatin-positive( when the sex chromatin is determined) and chromatin-negative( when no sex chromatin is detected).The incidence of Klinefelter's syndrome is 1 case per 400 newborn boys. Among mentally retarded children, Klinefelter's syndrome occurs in 1-2% of cases.
In typical cases of Klinefelter's syndrome, boys have high growth, sleep badly, quickly become fatigued, a narrow chest is characteristic, there is an increase in the mammary glands, a lack of testicles in the scrotum. However, these signs of the disease, as a rule, are found only in the period of puberty. Benign enlargement of the mammary glands and absence of testicles in the scrotum are found in about half of boys with Klinefelter's syndrome, so recognition of this syndrome at an earlier age presents significant difficulties. For many boys during puberty are characterized by eunuchoid body proportions. The testicles are small, soft to the touch, the formation of spermatozoa is disturbed. In the study of urine, hormones reveal characteristic changes.
In some cases, there are deformities of the teeth, fissures of fingers between each other, various abnormalities of the skeleton. Characteristic changes on the part of the respiratory organs, cardiovascular and digestive systems are not found. Endocrine disorders are often represented by obesity by the female type, benign enlargement of the mammary glands, underdevelopment of the penis and testicles. Often in boys, a female type of hair is defined. The peculiarity of the syndrome is the high incidence of breast cancer: 60 times higher than in the population.
In some cases, signs of damage to the nervous system may appear: pupil disparity( anisocoria), decreased muscle tone, disturbances in co-ordinatorial tests, etc. Individuals with Klinefelter's syndrome have abnormalities in the brain that are manifested by epileptic seizures. Significant changes are revealed in the mental sphere. Some of the boys are noted for dementia in the degree of debility, others retain normal intelligence. There is a decrease in mental activity, an inability to prolonged stress. A remarkable feature of Klinefelter's syndrome is the extreme variability of symptoms: from individuals that are outwardly normal, with a sufficiently reserved intelligence, to patients with eunuchoidism and morbidity. A common symptom of the disease is a different degree of impaired sperm formation and underdevelopment of the testes, a change in the content of hormones in the urine. The incidence of some diseases linked to the X chromosome( color blindness, hemophilia, etc.) streets with Klinefelter's syndrome is lower than in healthy boys.
In 1959, a chromosomal set of persons with Klinefelter's syndrome - 47, XXY - was described. A characteristic feature of the set of chromosomes was the presence of an extra X chromosome( 22 pairs of autosomes, two X- and one Y-chromosome).The presence of an additional X-chromosome causes a variety of disorders in the Klinefelter syndrome. In a significant number of skin cells, sexual chromatin is found. All persons with this syndrome have a male phenotype( appearance), hypoplasia of testicles, euthanism, debility. With an increase in the number of X-chromosomes( which may also be 3 and 4), the degree of decline in intelligence increases, and a tendency to develop developmental anomalies is found.
In the treatment of Klinefelter's syndrome, hormonal drugs are used. Positive results of treatment of benign enlargement of the mammary glands can be obtained during surgery.
Trisomy Syndrome X
A chromosomal set of 47 chromosomes( 47, XXX) was found in the girls with trisomy on the sex X chromosome. The incidence of trisomy X syndrome is 1 case per 1200 newborn girls. This syndrome can be manifested by a decrease in intelligence in an easy degree, menstrual cycle disorders or complete absence of menstruation. Quite often, the syndrome of trisomy X does not appear. In this case, girls can be capable of procreation. It is interesting to note that mothers with trisomy X are born normal children.
Significantly less common is the syndrome with four sex chromosomes: 48, XXXX.These girls usually show a mental retardation. With syndrome 49, XXXXX, the degree of intellectual decline is deeper. Sick girls have dwarf growth, various congenital malformations.