Swyer's syndrome

Among the rare congenital pathologies, Swyer syndrome stands out. This disease indicates a disrupted structure of the Y chromosome - for example, the absence of a particular gene, or its mutation.

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

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Epidemiology

Swyer syndrome is relatively rare, although experts point out that there is insufficient information regarding this type of pathology. Statistics estimate the frequency of the syndrome only approximately as one case per 80 thousand newborns.

Swyer syndrome is related to a mutation chain in the genes of the Y chromosome. Approximately 15% of patients suffering from this pathology have deletions in the SRY gene – we are talking about chromosomal rearrangements that occur with the loss of a chromosomal region. The SRY gene (Sex Determining Region Y) is localized in the Y chromosome and is involved in the development of the body according to the male phenotype.

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Causes of Swyer's syndrome

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

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

Mutational changes in the gene lead to the synthesis of an incorrect, "non-working" protein. The differentiation of Sertoli cells is disrupted. As a result, the seminiferous tubules are formed incorrectly and dysgenetic gonads are formed.

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

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Risk factors

To prevent or promptly recognize chromosomal abnormalities in the fetus during pregnancy, the doctor must ask the future parents about existing hereditary pathologies, living conditions, etc. As has been proven in several studies, gene mutations - including Swyer syndrome - largely depend on these factors.

Among other things, experts have identified a risk group that includes:

• parents, each of whom is over 35 years of age;
• families that have blood relatives with any diagnosed chromosomal abnormality;
• parents working in hazardous working conditions;
• parents who have lived for a long time in a region with an unfavorable environmental (radiation) background.

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

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Pathogenesis

Pathogenetic features of Swyer syndrome consist of incorrect information of the Y-chromosome - there is a violation of the activity of the locus that determines the sex and quality of development of the testicles. This locus is located in the p11.2 region of the Y-chromosome. Due to the impaired activity, underdevelopment of cellular structures that were originally supposed to become sex glands is observed. As a result, the production of sex hormones is completely blocked - both female and male.

If the body lacks adequate hormonal sex background, then development proceeds in a female manner. Based on this, a newborn child with XY chromosomes, or with a fragmentary Y chromosome, develops according to the female phenotype.

Girls with Swyer syndrome have congenital ovarian dysgenesis, which is detected mainly at the expected period of puberty. Even with the presence of fallopian tubes and genitals, patients do not show transformation of the gonads into ovaries. Uterine development is usually insufficient.

Patients with Swyer syndrome have an increased risk of gonadal malignancy, approximately 30-60%. To avoid complications, the gonads should be removed as early as possible.

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Symptoms of Swyer's syndrome

Until the child reaches puberty, the symptoms of Swyer syndrome are clinically absent. Only as the child grows older do the corresponding pathological signs appear:

• absence or poor hair growth in the pubic and armpit areas;
• underdeveloped mammary glands;
• "childish" uterus, sometimes against the background of vaginal hypoplasia;
• intersex body type variation;
• atrophic processes in the mucous tissue of the genital organs;
• underdevelopment of the external genitalia.

Puberty does not occur in patients with Swyer syndrome: the body does not produce the necessary hormones - estrogens. Most of these women have no menstrual cycle at all, or have minor menstrual-like discharge.

In older patients, Swyer syndrome and lymphangioleiomyomatosis may be combined - a rare polysystemic disease with increasing cystic destructive changes in the lung tissue. The lymphatic system is affected, angiomyolipomas are formed in the abdominal organs. The pathology is manifested by spontaneous pneumothorax, increasing dyspnea, and episodic hemoptysis. Such cases are isolated, but they are worth paying attention to.

Swyer Syndrome Body Features

It is impossible to distinguish a healthy girl from one with Swyer syndrome by external characteristics. Patients with the syndrome have a normal body build, adequate growth rates, and a formed external genital area. Many of them have physiologically normal development of the uterus and appendages, but hypoplasia is often present. Dysfunction of the ovaries is observed against the background of obvious modification of the organs.

Upon reaching puberty, the external signs of the syndrome become more pronounced in some patients. An intersexual or eunuchoid body type is observed: broad shoulders, narrow pelvis, tall stature, massive lower jaw, voluminous muscles.

During examination, connective tissue elements and glandular tissue inclusions are sometimes found instead of ovaries. Patients with Swyer syndrome are sterile - that is, they do not have follicle maturation, they have no eggs, and they cannot conceive a child naturally.

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Complications and consequences

As a rule, patients suffering from congenital Swyer syndrome always have difficulties with conceiving a child. The absence of a menstrual cycle, delayed sexual development - these signs most often become the reason for visiting a doctor, thanks to which the diagnosis of the syndrome is established.

However, for many patients with the syndrome, the desire to become a mother becomes a reality – thanks to the latest methods of reproductive medicine. The procedure of in vitro fertilization using donor eggs can solve such a problem.

Another serious complication of Swyer syndrome is the development of malignant tumors. This complication can also be avoided if the gonadal strands are removed as early as possible, especially if there are signs of virilization. To date, the reason why malignant tumors develop in patients with Swyer syndrome has not been established. However, the prognosis after exploratory surgery is positive in the vast majority of cases.

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Diagnostics of Swyer's syndrome

Swyer syndrome is detected in the vast majority of cases only after the patient reaches puberty. Girls do not demonstrate adequate sexual development, and there is no natural menstrual cycle.

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

When making a diagnosis, the level of gonadotropins in the blood plasma (FSH and LH), as well as the excretion of estrogens and the level of estradiol are necessarily taken into account.

Ultrasound examination allows to examine developmental defects of reproductive organs in case of syndrome. Additionally, the doctor may prescribe hysterosalpingography.

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Differential diagnosis

Differentiating the syndrome can sometimes be quite difficult – first of all, it is necessary to distinguish Swyer syndrome from other types of gonadal dysgenesis. Laparoscopic surgery with biopsy and karyotype assessment usually helps in identification.

Patients with Swyer syndrome do not have somatic defects or general developmental delays. Patients often have normal growth, but may have underdeveloped secondary sexual characteristics and significant sexual infantilism. Karyotype indicators are 46 XX or 46 XY.

In the mixed form of dysgenesis syndrome, virilization of the external genitalia is possible: the clitoris is slightly enlarged, and a connection of the lower segment of the vagina with the urethra may be observed.

In some cases, there is a need to differentiate Swyer syndrome from Shereshevsky-Turner syndrome, as well as from delayed sexual development of central origin.

Swyer syndrome is often confused with Swyer-James-McLeod syndrome. These pathologies have nothing in common and are fundamentally different from each other.

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Treatment of Swyer's syndrome

Considering that dysgenetic gonads have an increased oncological risk, they are removed as early as possible - in childhood, or immediately after the diagnosis of Swyer syndrome.

After surgery, all patients, starting from adolescence, are prescribed hormone replacement therapy. This allows for adequate formation of secondary sexual characteristics, and also serves as a preventive measure against bone system pathologies (osteoporosis).

Replacement treatment for Swyer syndrome should preferably be started at the age of 14-15. The preferred medications are conjugated estrogenic drugs (Premarin at a dosage of 625 mcg daily) and β-estradiol agents (Progynova at a dosage of 1 mg daily). It is permissible to apply estrogen preparations to the external skin: in such cases, for example, Divigel is used.

Hormonal therapy for the syndrome is usually long-term – until the expected normal onset of menopause (age around 50 years). Periodically during the hormonal course, the doctor evaluates the adequacy of the individually selected therapy.

Patients with Swyer syndrome do not have their own eggs. However, in some cases, it is possible to carry a pregnancy to term after the IVF procedure (donor cells are used).

Prevention

Preventive measures to prevent the development of Swyer syndrome and other chromosomal abnormalities in the fetus are usually complex and consist of several stages.

1. The first stage of prevention should be carried out at the stage of pregnancy planning. The goal of this stage is to eradicate the causes that can provoke the development of congenital defects or chromosomal failures. Parents of the future child should avoid the influence of all harmful factors on their health: harmful industrial emissions, poor-quality food, medications, bad habits, household chemicals, etc. About a couple of months before conception, a woman needs to take special multivitamins for pregnant women, as well as prevent the development of acute respiratory viral infections and influenza infections.
2. The second stage involves visiting a geneticist: it is necessary to determine the presence of unfavorable heredity and, if necessary, select the most effective method of family prevention.
3. The third stage of prevention of Swyer syndrome is carried out already during pregnancy. A woman should pay close attention to her health, not smoke, not drink alcohol, not take medications without a doctor's prescription. She should also eat right, spend enough time outdoors, etc.

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Forecast

All patients diagnosed with Swyer syndrome fall into the absolute infertility group. Even with a monthly cycle, pregnancy either does not occur or is strongly discouraged due to the increased risk of various complications and abnormalities in the future child.

Most patients are advised by doctors to have their gonads removed, as there is a high risk of developing a malignant tumor.

Swyer syndrome is a congenital, incurable pathology.

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