Description

Complete androgen insensitivity syndrome, or CAIS, is a sex development condition which affects people with a 46,XY karyotype. Because those with CAIS have an active SRY gene, they develop internal testes, but because their bodies do not respond to the sex hormone known as androgen, affected individuals are usually born with a female phenotype.

If you want to help improve medical research and psychological support for individuals with these conditions, you can donate to DSDFamilies (https://dsdfamilies.org/donate).

Sources

[1] NIH. (2020). Androgen insensitivity syndrome. Genetics Home Reference, National Library of Medicine.

[2] Oakes, M., et al. (2008). Complete androgen insensitivity syndrome--a review. Journal of Pediatric and Adolescent Gynecology, 21(6).

[3] Gottlieb, B., et al. (2017). Androgen Insensitivity Syndrome, Gene Reviews (NIH).

[4] Pizzo, A., et al. (2013). CAIS, a rare case of DSD. Case Reports in Obstetrics and Gynecology.

[5] Pritsini, F., et al. (2017). Psychological aspects of AIS. Case Reports in Endocrinology.

AIS support group:

https://www.aisdsd.org

Transcript

Complete androgen insensitivity syndrome, or CAIS, is a sex development condition which affects people with a 46,XY karyotype. Because those with CAIS have an active SRY gene, they develop internal testes, but because their bodies do not respond to the sex hormone known as androgen, affected individuals are usually born with a female phenotype.[1]

The condition affects every 1 in 50,000 to 1 in 20,000 newborns--a rate of around 0.002 to 0.005% of births.[2]

At conception, the chromosome set for CAIS begins with 46,XY. However, this X chromosome has a unique mutation in the androgen receptor gene (AR). The AR gene provides instructions for making proteins known as androgen receptors, which allow cells to respond to androgens for male sex development. Mutations in the AR gene results in no activity at the androgen receptors, so cells cannot respond to androgens. Without response to androgens like testosterone, the fetus develops a female body. In those with 46,XY, one altered copy of the AR gene in each cell is sufficient to cause CAIS.

Around the 8th week after conception, the 46,XY fetus undergoes gonadal differentiation. Because there is a Y chromosome with an active SRY gene, the bipotential gonads begin developing into testes. As the gonads differentiate into testes, they produce two hormones: anti-Mullerian hormone (AMH) and the androgen known as testosterone. Because the fetus cannot respond to testosterone, the Wolffian structure (which would have formed the epididymis, vas deferens, and seminal vesicle) does not develop fully, and the testes usually remain in the abdomen, undescended. Having been exposed to anti-Mullerian hormone, the Mullerian structure (which would have formed the fallopian tubes, uterus, cervix, and upper part of the vagina) disintegrates, but with no response to testosterone, the fetus does not masculinize, and the baby is born with female external genitalia.

Despite the active SRY gene which differentiates the gonads into testes, the androgens are unable to bind to androgen receptors for male sex development, and the infant is born with a female phenotype. Thus, newborns with CAIS are observed at birth as females, raised as females, and identify as females throughout life.[3]

CAIS is not usually diagnosed at birth. Like MRKH, which results in underdeveloped Mullerian structures, the common indicator for CAIS is that affected young women never start their periods.[4] Thus, most diagnoses occur between 15 and 18 years old. The diagnostic process utilizes a pelvic ultrasound to see whether the uterus is present and an MRI to show more detailed imagery of the internal reproductive anatomy. Because MRKH and CAIS both involve an absent uterus, clinicians will utilize karyotype and hormone testing to further narrow the diagnosis. If the karyotype comes back with 46,XY, rather than the 46,XX for MRKH, then the adolescent likely has CAIS. Once diagnosed, the doctors will refer the patient to a pediatric or adolescent gynecologist.[5]

Because some androgens are converted into estrogen through a process called aromatase, women with CAIS have typical female hormone levels, and because their body does not respond to elevated androgen levels, they develop a typical female phenotype.[6] They also go through puberty around the same time as their 46,XX counterparts, just without periods due to the absence of ovaries and a uterus. After puberty, it is sometimes recommended that women with CAIS get the internal testes surgically removed, since the testes have a chance of becoming cancerous.[7] But since the risk of malignancy is low, patients can also choose to keep the gonads to retain a natural source of androgen production.[8]

There are important psychological issues to address if one is diagnosed with CAIS. First, it is critical that a diagnosis of CAIS is not withheld from the patient. Doctors and parents of the patient have a moral obligation to accurately inform the individual about their condition, how it developed, and what the treatment options are. The method and timing of providing the information depends upon the patient's age and cognitive development.[9]

Second, a diagnosis of CAIS, like other sex development conditions, often leads to psychological distress, and it's critical that trained psychologists and counselors are involved. For patients with CAIS, a major component to understand is that they are healthy women, albeit infertile. Experts in CAIS reaffirm this: "As these girls have never been exposed to male androgen levels, their brain development, along with their physical development, is completely female."[10]

Unfortunately, unique sex development conditions like CAIS are often co-opted by activists who use these variations to push ideas about gender or identity. But individuals with DSDs like CAIS experience the same levels of variation in identity and expression as the general population.[11]

In conclusion, women with CAIS have a 46,XY karyotype with an active SRY gene, and therefore develop internal testicular tissue. Due to inactive androgen receptors, they develop typical levels of estrogen and a female phenotype. Like their 46,XX counterparts, they are observed at birth as females, raised as females, and identify as females. With patient-centered treatments focused on the health and psychology of the individual, and loving support from parents and peers, women with CAIS can live healthy lives, secure in their own bodies.

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© 2020 Zachary A. Elliott, All Rights Reserved.