Swyer Syndrome - The Science of Gender Diversity

Introduction

Swyer syndrome is a condition affecting normal sexual development. An individual affected by the conditions remains asymptomatic for a long time until the age of puberty is attained. The primary symptom associated with Swyer syndrome is delayed puberty and primary amenorrhea (absence of periods). The diagnosis is made with the help of detailed individual and family medical history, clinical physical examination, and several tests, including blood examinations and imaging tests. Treatment of Swyer syndrome is done with the help of hormone replacement therapy and surgical removal of underdeveloped gonads.

What Is Swyer Syndrome?

Swyer syndrome is a disorder affecting sexual development in an individual. Chromosomes determine sex and sexual development in an individual, but in the case of Swyer syndrome, sexual development is not specific to their chromosome pattern. Swyer syndrome is a rare condition, and it causes failure of the sex glands, ovaries in women, and testes in men, to develop properly. Swyer syndrome is categorized as a disorder of sex development (DSD), which includes any condition characterized by impaired chromosomal, gonadal, or anatomic sex development. Swyer syndrome is also considered a type of hypogonadism (failure of the gonads to function correctly) in which the affected individual has non-functioning gonads known as streak gonads. People with one X and Y chromosome, ordinarily found in men, are born with female genitalia and underdeveloped gonads in Swyer syndrome.

Other Names of Swyer Syndrome-

Alternative names for Swyer syndrome include:

• XY gonadal dysgenesis.

• 46, XY CGD.

• 46, XY sex reversal.

• Gonadal dysgenesis, XY female type.

• XY pure gonadal dysgenesis.

What Causes Swyer Syndrome?

• The cause of Swyer syndrome is uncertain in many people. In some people, however, variations or mutations in one of the multiple genes have been proven to be the cause of the condition.

• In about 15 percent of people with Swyer syndrome, variants in the SRY gene have been identified as the cause of the condition. SRY gene is a sex-determining gene on the Y chromosome, and it is responsible for providing instruction for the production of a protein known as protein-determining region Y.

• This protein initiates the mechanisms that lead to male sex development. Male gonads (testes) and genitals develop in a fetus as a result of these mechanisms, which hinder the development of female reproductive structures.

• Because only 15-20 % of women with Swyer syndrome have a variation in the SRY gene, experts suspect that the disorder could also be caused by a mutation in other genes.

• In some instances, mutations in the MAP3K1 gene (mitogen-activated protein kinase kinase kinase 1), DHH (desert hedgehog) gene, or NR5A1 (Nuclear receptor subfamily 5 group a member 1) gene can cause Swyer syndrome.

Is Swyer Syndrome a Common Condition?

Swyer syndrome is a rare condition, but the exact rate of occurrence is unknown because of fewer reported and documented cases. However, it is speculated that Swyer syndrome occurs in 1 in every 80,000 individuals globally. In addition, there are about 3,000 to 30,000 known cases of Swyer syndrome in America.

Is Swyer Syndrome a Hereditary Condition?

Swyer syndrome is not hereditary in most cases; it affects persons with no family history of the disorder. These situations are frequently the outcome of new variations. However, Swyer syndrome is inherited in some cases when it is caused by mutations in the DHH (desert hedgehog) gene.

What Are the Effects of Swyer Syndrome on the Reproductive System?

• Individuals affected by Swyer syndrome develop a vagina, uterus, and external genitalia, but not the related sex glands or the ovaries. Instead, they have streak gonads, in which the ovaries do not fully develop, resulting in the substitution by functionless connective tissue that does not release sex hormones.

• Swyer syndrome patients are infertile and unable to conceive naturally due to a lack of ovaries. In addition, due to the lack of ovaries, the hormones estrogen and testosterone are absent, which are crucial for the onset of puberty in a child. Therefore, these individuals do not undergo puberty. However, puberty can be attained if the condition is diagnosed early and the affected individual is given hormone replacement therapy.

What Are the Common Signs and Symptoms of Swyer Syndrome?

• Most people with Swyer syndrome do not present with any apparent physical symptoms until they reach the age of puberty.

• Teens affected by Swyer syndrome do not get their period (menstruation) even after reaching the age of 14. This condition is known as primary amenorrhea.

• Lack of sex hormones estrogen and progesterone due to lack of ovaries.

• Women affected by Swyer syndrome are usually taller than average and have a small uterus and enlarged clitoris.

• Swyer syndrome causes about 30 % of women to develop a tumor that originates from the cells that make the testes or ovaries. G gonadoblastoma, a non-cancerous tumor, is the most frequent gonadal tumor in women with Swyer syndrome.

• Gonadoblastomas may lead to the development of a cancerous tumor such as dysgerminoma, which has also been shown to occur more frequently in women with Swyer syndrome as compared to the general population.

• Hypogonadotropic hypogonadism is a disorder characterized by reduced or absence of production of sex hormones by the gonads. Moreover, hypogonadotropic hypogonadism is a condition in which hypogonadism occurs due to a dysfunctional pituitary gland or hypothalamus.

• Male pseudohermaphroditism is a condition in which the gonads and external genitalia have different morphologies.

• Polycystic ovaries mean there is a presence of multiple small cysts on the outer edge of the ovaries.

How Is Swyer Syndrome Diagnosed?

The diagnosis of Swyer syndrome is made in the following ways:

• A detailed clinical history, clinical examination, identification of distinctive features, and several tests are used to diagnose Swyer syndrome.

• Most cases of Swyer syndrome are tested during their teenage after a delay in puberty is noticed or there is primary amenorrhea.

• The karyotype of a person can be determined using a fluorescent in situ hybridization test. A karyotype is a test that depicts a person's chromosomal composition.

• Affected individuals are also advised to perform molecular genetic testing to see if they have one of the specific gene mutations linked to Swyer syndrome.

• Blood examinations are done to check the levels of sex hormones; estrogen, progesterone, and testosterone.

• An evaluation of the affected person's family members can determine whether the disorder is random or inherited.

• Imaging tests like ultrasonography, MRI (magnetic resonance imaging), and CT scans (computed tomography) are done to identify and study the internal reproductive organs and genitals.

How Is Swyer Syndrome Treated?

The treatment of Swyer syndrome involves a multifaceted approach and management. The therapies used to treat Swyer syndrome are:

• Swyer syndrome is treated with sex hormone replacement therapy, which includes the replacement of the two primary hormones produced by the ovaries, estrogen and progesterone. This treatment is typically started around the age of puberty to promote menstruation and the development of female secondary sexual characteristics.

• Hormone replacement therapy can help prevent bone loss and thinning and benefit the development of secondary sexual characteristics.

• Streak gonads are surgically removed because they increase the risk of developing benign gonadal tumors.

Conclusion

Swyer syndrome is a rare condition, and the individuals affected by this condition are infertile due to the absence of ovaries. The ovaries are responsible for the production of sex hormones estrogen and progesterone. These hormones are responsible for inducing puberty and developing feminine secondary sexual characters properly. Since the individuals affected by this condition are infertile, they require medical assistance to conceive (get pregnant). They can, however, become pregnant by the implantation of donated eggs. The increased risk of cancer of the undeveloped gonadal tissue is a primary medical concern for women with Swyer syndrome. Therefore, streak gonads are surgically removed.