Svayer syndrome

Of the rarely occurring congenital pathologies, Svayer syndrome is particularly prominent. This disease indicates a disordered structure of the Y chromosome - for example, the absence of a single gene, or its mutation.

The disease can have several names: it is often called female gonadal dysgenesis, or simply gonadal dysgenesis. The name of the Svayer syndrome occurred by the name of Dr. Gerald Svayer, who first described the pathology back in the 50s of the last century.

[3], [4], [5], [6], [7]

Epidemiology

Svayer syndrome is relatively rare, although experts point to a lack of information on this type of pathology. The frequency of the appearance of the syndrome is estimated by the statistics only approximately, as one case for 80 thousand newborn children.

Svayera syndrome has to do with the mutation chain in the Y chromosome genes. Approximately 15% of patients suffering from such a pathology show deletions in the SRY gene - it is a question of chromosomal rearrangements proceeding with the loss of the chromosomal site. The SRY (Sex determining Region Y) gene is localized in the Y chromosome and participates in the development of the body according to the male phenotype.

[12], [13],

Causes of the svayer syndrome

The most common cause of Svayer syndrome development is the microstructural transformation of the Y chromosome, accompanied by the loss of the SRY gene, along with point mutations of the voiced DNA region.

The SRY gene is located on the short arm of the Y chromosome. Its function is the coding of a protein that binds to genes that determine the sex of a future child according to a male phenotype.

Mutational changes in the gene lead to the fact that the wrong, "non-working" protein is synthesized. Differentiation of Sertoli cells is disturbed. As a result, the seminiferous tubules are improperly formed and the dysgenetic gonads are formed.

The formation of other organs of the sexual sphere proceeds according to the female phenotype, although there is a Y-chromosome in the karyotype.

[20], [21]

Risk factors

To prevent or timely recognition of chromosomal abnormalities in the fetus during pregnancy, the doctor should learn from future parents about existing hereditary pathologies, living conditions, etc. As it was proved in several studies, gene mutations - including, and Svayer's syndrome - from these factors.

Among other things, experts identified a risk group, which includes:

• parents whose age exceeds 35 years;
• family in which there are blood relatives with any diagnosed chromosomal abnormality;
• parents working in harmful industrial conditions;
• parents who live in the region for a long time with an unfavorable ecological (radiation) background.

All these factors significantly increase the risk of developing Svayer syndrome and other chromosomal abnormalities in the fetus, especially if there are hereditary pathologies at the gene level.

[23], [24], [26], [27], [28],

Pathogenesis

Pathogenetic features of the Svayer syndrome lie in the wrong information of the Y-chromosome - there is a disruption in the activity of the locus, which determines the sex and the quality of development of the testes. This locus is located in the p11.2 portion of the Y chromosome. Due to impaired activity, there is underdevelopment of the cellular structures, which initially had to become sex glands. As a result, the production of sex hormones, both female and male, is completely blocked.

If the body lacks an adequate hormonal sexual background, then the development follows a female image. On this basis, a newborn baby with chromosomes XY, or with a fragmentary Y-chromosome develops according to the female phenotype.

Girls with Svayer syndrome have congenital ovarian dysgenesis, which is found mainly during the period of expected puberty. Even in the presence of the fallopian tubes and genitals, the patients do not experience gonadal transformation into the ovaries. Development of the uterus, as a rule, is insufficient.

Patients suffering from Svayer syndrome have an increased risk of gonad malignancy - about 30-60%. To avoid complications, gonads should be removed as soon as possible.

[32], [33], [34]

Symptoms of the svayer syndrome

Until the moment the child enters the sexual maturity period, the symptoms of Svayer syndrome are not clinically present. Only in the course of growing the corresponding pathological signs are found:

• absence or small expression of the hair in the pubic region and armpits;
• small development of mammary glands;
• "Child" uterus, sometimes against a background of vaginal hypoplasia;
• intersexual variation of build;
• atrophic processes in the mucous tissue of the genital organs;
• underdevelopment of external genital organs.

Sexual maturity in patients with Svayer syndrome does not occur: the body does not produce the necessary hormones - estrogens. Most of these women completely lack a monthly cycle, or there are minor menstrual-like secretions.

In more mature age, patients can combine Svayer syndrome and lymphangioleiomyomatosis - this is a rare polysystemic disease, with increasing cystic destructive changes in lung tissue. The lymphatic system is affected, angiomyolipomas are formed in the organs of the abdominal cavity. Pathology is manifested by spontaneous pneumothorax, increasing dyspnea, episodic hemoptysis. Such cases are rare, but they should be paid attention.

Features of the body with Svayer syndrome

By external characteristics it will not be possible to distinguish a healthy girl from a patient with Svayer syndrome. Patients suffering from the syndrome inherent in the addition of the body within the norm, adequate growth rates and the formed external sexual sphere. Many of them show a physiologically normal development of the uterus and appendages, however, hypoplasia is often present. Dysfunction of the ovaries is observed against the background of an obvious modification of the organs.

When the sexually mature age is reached, the external signs of the syndrome are more pronounced in some patients. There is an intersexual or eunuchoid type of physique: broad shoulders, narrow pelvis, high growth, massive lower jaw, volumetric muscles.

During the examination, instead of the ovaries, connective tissue elements are sometimes found, inclusions from the glandular tissue. Patients with Svayer syndrome are sterile - that is, they do not ripen follicles, there are no ovules, they can not conceive a child in a natural way.

[35], [37], [38],

Complications and consequences

As a rule, patients with congenital Svayer syndrome always have difficulty in conceiving a child. Absence of a monthly cycle, delay in sexual development - these signs are often the reason for visiting a doctor, due to which the diagnosis of the syndrome is established.

Nevertheless, for many sick with the syndrome the desire to become a mother becomes a reality - thanks to the newest methods of reproductive medicine. The procedure of in vitro fertilization with the use of donor eggs is able to solve a similar problem.

Another formidable complication of Svayer syndrome is the development of malignant tumors. This complication can also be avoided if gonadal strands are removed as early as possible - especially if signs of virilization are present. To date, no reason has been established for the development of malignant tumors in patients with Svayer syndrome. However, the forecast after the exploratory operation is overwhelmingly positive.

[40], [41]

Diagnostics of the svayer syndrome

Detect Svayer syndrome in the vast majority of cases only when the patient reaches the sexually mature period. Girls do not demonstrate adequate sexual development, there is no natural monthly cycle.

In some cases, the syndrome is diagnosed already at the stage of dysplasia or malignancy of the dysgenetic gonads. The final diagnosis of "Svayer syndrome" is established after genetic analysis with the definition of a male karyotype in a female patient (46 XY).

When the diagnosis is made, the level of gonadotropins in the blood plasma (FSH and LH) must be taken into account, as well as estrogen excretion and the level of estradiol.

Ultrasound examination allows us to consider the developmental defects of reproductive organs in the syndrome. Additionally, the doctor may prescribe a hysterosalpingography.

[43], [47], [48]

Differential diagnosis

Sometimes it is difficult to differentiate the syndrome - in the first place, it is necessary to distinguish Svayer syndrome among other types of dysgenesis. In identification, laparoscopic surgery usually involves taking a biopsy and assessing the karyotype.

For patients with Svayer syndrome, there are no physical defects and a general developmental delay. Often patients have normal growth, but may have underdevelopment of secondary sexual characteristics and significant sexual infantilism. Karyotype parameters are 46 XX or 46 XY.

With the mixed form of the dysgenesis syndrome, virilization of the external genital organs is possible: the clitoris is slightly enlarged, the connection of the lower segment of the vagina with the urethra can be observed.

In some cases, there is a need for differentiation of Swier's syndrome with Shereshevsky-Turner syndrome, as well as with the delayed sexual development of the central origin.

According to the writing, Svayer syndrome is often confused with Svayer-James-McLeod syndrome. These pathologies have nothing in common and are fundamentally different from each other.

[50], [51], [52]

Treatment of the svayer syndrome

Given that the dysgenetic gonads have increased cancer risk, they are removed as soon as possible - in childhood, or immediately after determining the diagnosis of Svayer syndrome.

After surgical intervention, all patients, beginning with adolescence, are prescribed hormone replacement therapy. This allows to achieve adequate formation of secondary sexual characteristics, and also serves as the prevention of pathologies of the osseous system (osteoporosis).

It is advisable to begin substitution treatment with Svayer syndrome from 14-15 years. Preferred medications are conjugated estrogen preparations (Premarin in a dosage of 625 μg daily) and β-estradiol (Proginova in a dosage of 1 mg daily). It is acceptable to apply estrogen preparations to the external skin: in such cases, for example, Divigel is used.

Hormonal therapy with the syndrome is usually prolonged - until the expected normal onset of menopause (age about 50 years). Periodically, during the hormonal course, the doctor evaluates the adequacy of individually selected therapy.

Patients with Svayer syndrome do not have their eggs. Nevertheless, in some cases it is possible to endure pregnancy after the IVF procedure (donor cells are used).

Prevention

Preventive measures to prevent the development of fetal syndrome Svayer and other chromosomal abnormalities are usually complex, consisting of several stages.

1. The first stage of prevention should be carried out at the planning stage of pregnancy. The goal of this stage is to eradicate the causes that can trigger the development of congenital malformations or chromosomal abnormalities. Parents of the unborn child must avoid the influence of all harmful factors on their health: harmful industrial emissions, poor-quality food, medicines, bad habits, household chemicals, etc. Approximately a couple of months before conception, a woman should take special complex vitamins for pregnant women, and also warn development of acute respiratory viral infection and influenza infection.
2. The second stage is to visit the genetics: it is necessary to determine the presence of adverse heredity and, if necessary, to choose the most effective way of family prevention.
3. The third stage of the Svayer syndrome is carried out during pregnancy. A woman should take good care of her health, do not smoke, do not drink alcohol, do not take medicine without prescribing a doctor. Also it is necessary to eat correctly, it is enough to be on fresh air, etc.

[54], [55], [56], [58], [59], [60], [61],

Forecast

All patients diagnosed with Svayer syndrome fall into the group of absolute infertility. Even in the presence of a monthly cycle, pregnancy either does not occur, or is strongly discouraged, because of the increased risk of various complications and anomalies in the unborn child.

Most doctors advise to remove gonads, since there is a high risk of developing a malignant tumor.

Svayer syndrome refers to congenital incurable pathologies.

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