What is Androgen Insensitivity Syndrome in Babies?

What is Androgen Insensitivity Syndrome?

Androgen Insensitivity Syndrome or AIS is a genetic condition caused by a disease causing variant or mutation of the AR (Androgen Receptor) gene on the X chromosome where the male baby is born with partial or complete inability to respond to androgens, the male sex hormones in the body causing the baby to have female physical attributes, male genetic make up with either ambiguous or female or underdeveloped male genitalia and infertility typical to all cases.

Even though the baby has female genitalia, it lacks ovaries, fallopian tubes and uterus and may have internal male reproductive organs like undescended testes in the pelvis or abdomen.

Androgen Insensitivity Syndrome Types

There are three types of Androgen Insensitivity Syndrome based on the extent of insensitivity to Androgens

1. Complete Androgen Insensitivity Syndromes (CAIS): The baby has complete insensitivity to androgens, the body does not respond at all to androgens and has no male external genitalia (may have internal testes) instead has female external genitalia and hence appear as girls at birth and are often raised as girls. They lack female internal sex organs like fallopian tube, ovaries and uterus so never menstruate or conceive in the future.

2. Partial Androgen Insensitivity Syndromes (PAIS): The body partially responds to Androgens and hence the baby may have both male and female attributes. The baby may have partially developed female or male genitalia or ambiguous genitalia with both gender characteristics.

3. Mild Androgen Insensitivity Syndromes (MAIS): The body has only mild insensitivity to androgens so baby will have typical external male genitalia but will still experience infertility in most cases and may even have enlarged breasts at puberty.

Androgen Insensitivity Syndrome Causes:

Androgen insensitivity syndrome is caused by a disease causing variant or mutation of the AR (Androgen Receptor) gene on the X chromosome that is passed from the mother to the child. The AR gene provides instructions for the Androgen Receptor, a protein to bind with the androgens and eventually help in the expression of the genes responsible for male sexual development and function, which does not happen in case of Androgen Insensitivity Syndrome due to the mutation.

Androgen Insensitivity Syndrome Symptoms:

In all types of Androgen Insensitivity Syndrome infertility is common. As the babies have no internal sex organs in case of CAIS, they cannot get pregnant and in case of PAIS and MAIS it is very rare for them to get their partners pregnant as the sperm count could be extremely low to non existent. There are many symptoms specific to each type and others that are common across as mentioned below:

Symptoms common to CAIS:

• Tall stature for a girl

• No menstrual periods

• Breast enlargement at puberty

• Undescended testes

• Shallow narrow vagina

• Groin hernia

• Little to no body hair, especially underarms and pubic hair

Symptoms common to PAIS:

• Very small penis (Micropenis)

• Labial fusion

• Enlarged breasts at puberty

• Large Clitoris

• Midline split of scrotum

• Urethral opening at underside of penis rather than tip

• No female internal sex organs

• Little to no body hair, especially underarms and pubic hair

Symptoms common to MAIS:

• Very small penis (Micropenis)

• Breast enlargement at puberty

• Little to no body hair, especially underarms and pubic hair

Androgen Insensitivity Syndrome Diagnosis:

Androgen Insensitivity Syndrome is diagnosed during a thorough physical exam after birth in case of a partial Androgen Insensitivity Syndrome (PAIS) while in case of CAIS and MAIS it may not be until much later during puberty when they do not menstruate or the external male sex organs don't develop as they should.

Tests that can confirm the diagnosis:

• Ultrasound: An ultrasound scan can detect the absence of female internal sex organs.

• Genetic testing: To analyse DNA for changes in genes, chromosomes and proteins to confirm the diagnosis.

• Blood Tests: Blood test can confirm any genetic abnormalities and levels of sex hormones.

Androgen Insensitivity Syndrome Treatment

Treatment is target at two levels, one is to help with the symptoms and physical appearance and the other is to help with gender identity. It is advisable to wait until the child crosses puberty to actively engage them in the decision making and gender assignment.

Children decided to be raised as male:

• Breast reduction surgery can be done post puberty once the child is old enough.

• Removal of undescended testes post puberty once they have fully developed to avoid the risk of cancer in the future. However, some experts believe testes should be removed earlier so talk to your healthcare provider on what works best for your child.

• Surgery to reshape the male genitalia to give a more male sex organ appearance.

• Androgen or hormone therapy to deepen the voice, grow facial hair and enhance male characteristics.

• Surgery to close the groin hernia

Children decided to be raised as female:

• Estrogen replacement therapy to enhance the female characteristics, prevent osteoporosis and for overall health and well being.

• Vaginal dilation to increase the length in case of short vagina

• Surgery to reshape the female genitalia and provide more feminine appearance.

Androgen Insensitivity Syndrome Outlook:

Children with Androgen Insensitivity Syndrome can go on to live normal healthy lives with many responding really well to hormone therapy and surgery to enhance the genitalia appearance however, they may not be able to have children as in most cases it causes infertility. Without timely gonadectomy the chances of cancer increases over 30%.

Gender assignment is both tricky and a very sensitive subject that needs to be handled with outmost care involving the opinion and the choices of the child. There is a high chance of psychological and social effects of the appearance growing up in kids and the effects of infertility later in young adults that needs professional help and counselling to manage and cope with.