Gonadal differentiation anomalies
The basis for the development of gonadal( gonadal gland) differentiation abnormalities is the quantitative or qualitative anomalies of the sex chromosomes, leading to a disruption in the formation of the primary lining of the gonads, from which the ovaries are subsequently formed in women and testes in men. This process is carried out at the 6-10th week of intrauterine development and requires a full set of sex chromosomes( XX in girls and XY in boys).
"Pure" gonad agenesis( set of sex chromosomes XX). This disease is characterized by the female structure of the external and internal genital organs. Sex glands are represented in the form of connective tissue strands( shoots).The alleged cause of the disease is the mutation of the gene necessary for the normal development and functioning of the ovary. In the period of puberty, mammary glands do not develop, there is primary amenorrhea( absence of menstruation).When studying the hormonal background, characteristic deviations in the form of low levels of female sex hormones are revealed. The disease is often combined with neurological disorders: deaf-mute, a violation of coordination of movements. The choice of the female is beyond doubt. In the period of puberty, such women are treated with hormonal drugs. In the literature there are descriptions of family cases of the disease.
"Pure" gonad agenesis( set of sex chromosomes XY) .It is characterized by the female structure of the external and internal genitalia, the presence of the genital glands in the form of stems( fibrous cords), sexual underdevelopment in the period of puberty. Sometimes there is a slight transformation of the external genitalia in the form of a hypertrophic clitoris. The disease is often combined with neurological and renal congenital anomalies. There is a high risk of developing a tumor of the sexual glands during puberty. Surgical removal of the steric gonad( gonads) is mandatory in this disease. In the pubertal period( puberty period), therapy is carried out with female sex hormones.
Syndrome Shereshevsky-Turner( gonadal dysgenesis) .In most cases, it is characterized by X chromosome monosomy( 45, X0), less often loss of the X chromosome region or its structural anomaly. In Shereshevsky-Turner syndrome, there are other variants of a set of sex chromosomes: 45, X0, 45, XO / 46, XX, 46, XX / loss of the X-chromosome, 46, XX / isochromosome, ring X chromosome, 45, XO /46, XY.Anomalies of the X chromosome lead to a disruption in the manifestation of genes that control the development and function of the ovaries, as a result of which fibrous strands are formed at the location of the ovaries( arrow gonads).In addition, genes that control the growth and differentiation processes of normal body cells suffer, which leads to a decrease in the final growth and the development of a variety of congenital developmental anomalies.
Disease is one of the most common causes of hypogonadism( hypoplasia of the gonads) in girls. In the newborn period, characteristic signs are a decrease in body height and weight at birth, swelling of the legs and feet. Disease due to X chromosome monosomy and annular X chromosome is characterized by pronounced external features: a shortened neck, pterygoid folds of the neck, a semilunar fold of the skin at the inner corner of the eye, a "gothic sky", a shortening of metacarpal bones, and many others.cardiovascular system, renal anomalies( omission of the kidney, its rotation).A distinct growth retardation in children with the Shereshevsky-Turner syndrome is observed at 6-7 years, progressing further because of the lack of a growth jump during puberty that occurs in healthy children, and the final growth of such children usually does not exceed 140-150 cm. The development of the skeletal bone slightly lags behind the age of the child. The production of growth hormone is not disrupted, however, in the period of puberty, the formation of growth hormone can be reduced as a result of the absence of sex hormones. During puberty in 92% of children secondary sexual characteristics are completely absent, primary amenorrhea( complete absence of menstruation) is observed. Secondary hair is developed by 12-13 years due to the effects of male sex hormones formed in the adrenal glands. In rare cases, a spontaneous period of sexual development and menstrual function may occur, which is quickly exhausted.
The detection of this disease is based on karyotyping( research of a set of chromosomes) and the detection of X chromosome monosomy or other possible variants of the syndrome. Given the high incidence of Shereshevsky-Turner syndrome, the study of a set of chromosomes is carried out in all girls with a pronounced growth retardation and the absence of secondary sexual characteristics at the onset of puberty.
When treating children with the syndrome of Shereshevsky-Turner solve two main problems: correction of short stature and underdevelopment of the sex glands. Currently, there is no single method of correcting the growth in this disease. It is possible to use anabolic steroids, which stimulate the metabolism and thereby contribute to the growth of the child( oxandrolone 0.05-0.1 mg / kg per day, retabolil 1.0 mg per month).The use of growth hormone preparations in a dose of 0.5 to 1.8 U / kg per week is becoming more widespread. Perhaps the combined use of growth hormone and anabolic steroids or estrogens( female sex hormones).Replacement therapy with sex hormones begins when you reach 12-13 years of age. After achieving the effect( development of the mammary glands, the development of the sexual glands according to the female type) cyclical therapy is prescribed by the same drugs that are used for hormone replacement therapy.
Mixed dysgenesis of testicles( asymmetric gonadal dysgenesis). This disease is characterized by asymmetric formation of gonads( gonads), in which there is a stitch on one side and testes on the opposite side. Most of these people detect chromosomal abnormalities in the form of 45, XO / 46, XY.When recruiting chromosomes 46, XY, structural anomalies of the male Y chromosome are possible.
External genitalia at birth are bisexual, that is, they outwardly resemble the structure of both female and male genital organs. The penis is well formed. All persons with this disease have female internal genitalia: the uterus, uterine( fallopian) tubes, which are formed mostly from the side of the arrow( degeneration of the reproductive gland into a fibrous cord).At external survey it is possible to note the same features which are characteristic for a syndrome of the Shereshevsky-Turner. During sexual development, a satisfactory formation of secondary male sexual characteristics is possible due to the preserved androgen-producing( male sex hormones-androgens) function of the testicle. It is possible to fully adapt to the male sex after appropriate surgical correction of the external genitalia and the obligatory removal of the pathologically altered sexual gland in connection with the danger of developing its tumor.
Bilateral dysgenesis of testicles( false male hermaphroditism, rudimentary testicle syndrome) is characterized by bilateral underdevelopment of testicles with insufficient function, mild development of the male genitalia and female genital organs. The set of sex chromosomes in this disease does not differ from the normal male( XY), the structural anomalies of the male Y chromosome are often combined with congenital renal anomalies and Wilms tumor. In the period of puberty, all the characteristic signs of hermaphroditism appear. There is a high risk of developing swelling of the sex glands. The lack of functional ability of the testicles to produce testosterone( male sex hormone) dictates the choice of the female, which is achieved by correcting the external genitalia with the formation of female external genital organs and the mandatory removal of the underdeveloped male sex glands. In the period of puberty, substitution therapy with female sex hormones is carried out.
True hermaphroditism( syndrome of bisexual gonads) is an extremely rare disease in which an individual has both ovarian and testicular tissue elements. Identify this form of hermaphroditism is possible only on the basis of a morphological study of the sex glands. With true hermaphroditism, the elements of female and male tissue can be mixed or separately in one sexual gland and may be located in two separate sex glands( i.e., one gland in this case is represented by the testicle and the other by the ovary).
The reasons for this state are not clear at this time. Most often, the set of sex chromosomes corresponds to the normal female( 46, XX), less often to the male sex( 46, XY).At present, people are more inclined to think about the possibility of transferring a site of the male Y chromosome to a female X chromosome. The supposed cause of mosaicism 46, XX / 46, XY is also considered the double fertilization of the same ovum with the subsequent formation of bisexual gonads( gonads).
External genitalia in this disease have a bisexual structure, but very rarely there are people who have a normal female or male structure of the external genitalia. In almost all cases of true hermaphroditism, the internal genitalia retain the female type( presence of the uterus, fallopian tubes, vagina).In the period of puberty, there may be signs of adulthood( an increase in the clitoris, a male type of hair, a rough voice) or the development of female secondary sexual characteristics( enlargement of the mammary glands, the onset of menstruation), depending on the degree of functional activity of the sexual glands.
The choice of the sex of the child depends on the degree of integration of the external genitalia and the functional activity of the testicle and the ovary. The pathologically altered tissue of the sex glands is subject to compulsory removal because of the risk of malignancy. If a female is selected, the testicle tissue is removed and the external genitalia is plasticized for the female type. The choice of the male is recommended only with full confidence in the presence of full-length testicles. Hormonal therapy is performed during puberty in accordance with the selected sex in cases where the gonads are removed completely. The remaining tissue of the ovary or testicle usually completely provides the body with sex hormones.