Androgen insensitivity syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Androgen insensitivity syndrome is a condition that affects sexual development before birth and during puberty. People with this condition have one X chromosome and one Y chromosome in each cell. In people with androgen insensitivity syndrome, the body's cells and tissues are unable to respond to certain male sex hormones (called androgens) that are important for normal male sexual development before birth and during puberty. As a result, affected individuals may have external sex characteristics that are typical for females or have features of both male and female sexual development.

There are three forms of androgen insensitivity syndrome: complete, partial, and mild.

Complete androgen insensitivity syndrome occurs when the body does not respond to androgens at all. People with this form of the condition have external sex characteristics that are typical of females. Affected individuals do not have a uterus. They have male internal sex organs (testes) that are undescended, which means they are located in the pelvis or abdomen instead of outside the body. As such, affected individuals do not menstruate and are unable to conceive a child (infertile). People with complete androgen insensitivity syndrome also have sparse or absent hair in the pubic area and under the arms.

The partial and mild forms of androgen insensitivity syndrome occur when the body's tissues are partially sensitive to the effects of androgens.

People with partial androgen insensitivity can have genitalia that look typical for females, genitalia that have both male and female characteristics, or genitalia that look typical for males.

People with mild androgen insensitivity are born with male-typical sex characteristics, but they are often infertile and tend to experience breast enlargement at puberty.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the AR gene cause androgen insensitivity syndrome. This gene provides instructions for making a protein called an androgen receptor. Androgen receptor proteins interact with androgen hormones, such as testosterone, and help direct male sexual development. Specifically, the androgen receptor attaches (binds) to androgen .cf0{font-family:Segoe UI;font-size:9pt;}hormones to form an androgen-receptor complex. This complex then binds to DNA to regulate the activity of certain genes that play a role in male sexual development. Androgens and androgen receptors also have other important functions in both males and females, such as regulating hair growth and sex drive.

Variants in the AR gene prevent androgen receptors from working properly, which makes them less able to bind to testosterone and regulate gene activity. If androgen receptors cannot bind to androgens, the body cannot use androgens, even if there are normal levels of these hormones in the body.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a variant would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that both copies of a gene would be altered, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

About 70 percent of all cases of androgen insensitivity syndrome are inherited from people who carry an altered copy of the AR gene on one of their two X chromosomes. The remaining 30 percent of cases result from new (de novo) variants in the gene that occur in the egg cell before the child is conceived or during early embryonic development.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Complete androgen insensitivity syndrome affects 2 to 5 in 100,000 newborn females. Partial androgen insensitivity is thought to be at least as common as complete androgen insensitivity. Mild androgen insensitivity is much less common.

Which doctor should you see?

The suggested department for discussing Androgen insensitivity syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Androgen insensitivity syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.