Swyer syndrome is a violation of the formation of sex, characterized by karyotype 46XY, congenital gonadal dysgenesis in the primary formed other female genitalia – vagina, uterus, fallopian tubes. The signs of pathology include primary amenorrhea, masculine physique, sexual infantilism. The diagnosis is made on the basis of anamnestic data, the results of general and gynecological examination, introscopic methods of pelvic examination, hormonal and molecular genetic analysis. Treatment consists of two stages – removal of undeveloped sex glands and long-term use of hormone replacement therapy.
General information
Swyer syndrome (complete or “pure” gonadal dysgenesis) can be briefly characterized as a female phenotype with a male genotype. The disease is named after the British endocrinologist Gerald Swyer, who described it in 1955 as a case of male pseudohermaphroditism. The full form of dysgenesis is nonsyndromic (not accompanied by extragenital malformations), excludes the duality of sexual development (the presence of male primary sexual characteristics along with female ones), psychological development occurs according to the female type. Congenital pathology occurs in one case per 20,000 individuals with a male karyotype and is registered more often than other forms of XY-gonadal dysgenesis.
Causes
The etiology of Swyer syndrome has not been sufficiently studied. To date, it is known that most often the occurrence of pathology is associated with the absence or mutation of the SRY gene, located on the short arm of the Y chromosome and mostly responsible for controlling the formation of testicles. Judging by the observations of family cases of the disease, the involvement of as yet unknown X-linked or autosomal genes is possible.
Risk factors are also not fully established. In addition to the general mutagenic effects (ionizing radiation and intoxication, viral infections, unbalanced or reduced nutrition) and the already mentioned hereditary burden, it is assumed that the probability of pathology may be directly dependent on the age of the father. Most often, it is not possible to trace the links between any effect on the body during gestation and the development of Swyer syndrome.
Pathogenesis
The formation of reproductive organs occurs from the Muller duct in women and the Wolf’s duct in men. In an embryo with a male genotype, the synthesis of male steroid hormones by Leydig cells in the embryonic testes is due to the influence of maternal chorionic gonadotropin. Sertoli cells stimulate the differentiation of Leydig cells and others, produce an anti-muller hormone that promotes atrophy of the Muller duct. Their normal activity causes the development of a male individual – with adequate differentiation of the testicles, atrophy of the Muller duct.
Pronounced failures of this mechanism lead to the formation of bi-potent rudiments of female reproductive organs, the development of which does not require such complex regulation. The maturation of the male embryo is controlled by the SRY gene. In its absence or mutation, the activity of Sertoli cells is disrupted, gonad differentiation does not occur, which leads to the development of Swayer syndrome – a phenotypically female organism without full-fledged ovaries capable of further stimulating the development of secondary sexual characteristics, but with useless, malignancy-prone rudiments of glands.
Symptoms
In the pre-pubertal period, pathology proceeds without any subjective manifestations. During puberty, Swyer syndrome is characterized by the absence of signs of puberty. There may be only scant hair loss in the pubic and armpits, but it is often absent. Menarche does not occur, the mammary glands do not develop or are very poorly expressed. The type of physique in ovarian dysgenesis is male – with broad shoulders, a voluminous chest, a narrow pelvis.
Women with Swyer syndrome are more likely to have normal or above average height, developed musculature, and a “heavy” lower jaw. Sometimes there is a slight hypertrophy of the clitoris, although usually the external genitals are somewhat underdeveloped. Patients complain of primary infertility, discomfort or pain due to insufficient development of the vagina during sexual intercourse or gynecological examination.
Complications
A frequent (in 20-60% of patients) complication of Swyer syndrome is the development of tumors, mostly originating from a rudimentary sexual cord, which, in fact, are represented by dysgenetic gonads – dysgermin, androblast. These neoplasias often have a malignant character, occur on both sides (synchronously or metachronically), are registered in early reproductive, adolescence and childhood.
The consequences of untreated Swyer syndrome can also include the early appearance of pathologies caused by estrogen deficiency in women – osteoporosis, cardiovascular diseases (arterial hypertension, coronary heart disease). In addition, for many patients, the diagnosis becomes a source of severe psychological suffering about the “loss of femininity”, and for married women – and fear of family breakdown.
Diagnostics
Diagnosis of Swyer syndrome is carried out by a gynecologist with the participation of a medical geneticist. Most often, the diagnosis is made at the age of 14-15 when contacting a doctor about the lack of sexual development, sometimes later, due to infertility. In some cases, the first sign of the disease and the basis for an in-depth study is a tumor formation of rudimentary sex glands, accidentally discovered by a doctor or by the patient herself. Diagnostic measures include:
- Clinical examination. During the general examination, the absence of the main secondary female sexual characteristics against the background of normal or accelerated growth is revealed. Gynecological examination reveals normally formed, but underdeveloped female external genitalia. Indirect confirmation of the diagnosis is the presence of blood relatives with complete or partial gonadal dysgenesis.
- Radiation research methods. The most accessible and informative diagnostic method is gynecological ultrasound. Ultrasonography makes it possible to detect such objective signs characteristic of pathology as uterine hypoplasia, convoluted, underdeveloped fallopian tubes, heavy-shaped “ovaries” (sometimes with neoplasms). In doubtful cases, an MRI is prescribed.
- Hormonal analysis. A characteristic feature of Swyer syndrome is a significant increase in gonadotropic (follicle-stimulating, luteinizing) hormones in the blood serum, a decrease in the level of estradiol. The gestagen functional test is negative, the cyclic (estrogen-gestagen) hormonal test is positive.
- Genetic testing. It is used for the purpose of verifying the diagnosis. Cytogenetic examination reveals the male karyotype (46, XY), and molecular genetic examination reveals the absence or damage of the SRY gene. If genetic examination is not possible, a histological examination of the ovarian biopsy is prescribed. The diagnosis is confirmed by the connective tissue structure with the absence of follicles.
Swyer syndrome is differentiated with other forms of gonadal dysgenesis – Shereshevsky-Turner syndrome, mosaicism 45,X/46, XY, Morris syndrome (testicular feminization syndrome), as well as with delayed sexual development of hypothalamic-pituitary, constitutional, idiopathic genesis. If a tumor is suspected, a consultation with an oncogynecologist is necessary, and an endocrinologist is needed to identify the central forms of puberty delay.
Treatment of Swyer syndrome
Conservative therapy
The treatment of the disease is aimed at preventing complications, normalizing the psychoemotional status of the patient, and, if possible, at the realization of reproductive function. After the diagnosis is established, a surgical operation is performed (removal of rudimentary gonads), then hormone therapy is prescribed. Early (from adolescence) initiation of treatment for Swyer syndrome increases the likelihood of carrying a child.
Hormone replacement therapy. It is carried out by alternating estrogenic and progestin drugs during menstrual cycles. It is prescribed from puberty to the age of menopause. Treatment normalizes the course of metabolic processes, promotes the development of the uterus, female genital secondary signs, gravidar preparation of the endometrium.
Correction of neuropsychiatric disorders. Psychotherapeutic influence on the personality allows you to rebuild the patient’s attitude to yourself and the immediate environment, transform your own psychological attitudes, relieve psycho-emotional stress. Sometimes the treatment is supplemented with pharmacotherapy (antidepressants, tranquilizers).
With sufficient development of the uterus, it is possible to use an IVF program with implantation of donor oocytes fertilized with the sperm of the patient’s spouse. During the gestation of the fetus, a woman is prescribed first supportive, then preserving hormone therapy. Delivery is carried out promptly. In modern reproductology and obstetrics, successful experience of pregnancy management has already been accumulated in patients with gonadal dysgenesis (including Swayer syndrome).
Surgical treatment
Surgical intervention in the volume of removal of rudimentary gonads and fallopian tubes is performed immediately after the diagnosis of this form of congenital ovarian agenesis. Surgical treatment is carried out in order to prevent neoplasms, the source of which are the cells of the dysgenetic sex glands. Conservative treatment is not recommended to begin before surgery, because hormone therapy increases the risk of cancer complications.
Prognosis and prevention
With timely rational treatment of Swyer syndrome, the prognosis regarding the duration and quality of life is favorable. Some patients can realize childbearing function with the help of assisted reproductive technologies, cases of repeated successful pregnancies are described. Primary prevention of the birth of girls with XY-dysgenesis includes a healthy lifestyle during pregnancy, the exclusion of occupational and household hazards. For early detection and treatment of the disease, monozygotic twins of patients should be subjected to genetic examination.
