Androgen insensitivity syndrome

Overview

Androgen insensitivity syndrome (AIS) affects the development of a person's genitals and reproductive organs.

The 2 types of AIS are called complete androgen insensitivity syndrome (CAIS) and partial androgen insensitivity syndrome (PAIS).

The genitals of a person with CAIS appear female.

The genitals of a person with PAIS may appear as female or male. Sometimes PAIS is discovered because a baby's genitals are not as expected for a baby boy or baby girl.

There are specialist healthcare psychologists who can help people with AIS understand their bodies and sex development.

The sex development of people with AIS means they will not be able to become pregnant or make their partner pregnant. However, there is help and advice on other ways to become parents if that is wanted.

What causes AIS?

AIS is caused by a genetic fault that's usually passed along the female line to the child.

Although people with AIS have XY (usual male pattern) chromosomes, the body does not respond to testosterone (the sex hormone) fully or at all. This prevents the sex development of a typical male.

A penis does not form or is underdeveloped. This means the child's genitals may develop as female, or are underdeveloped as male.

The child may have have fully or partially undescended testicles. But there will be no womb or ovaries.

Women who carry the genetic alteration will not have AIS themselves, but there's a 1 in 4 chance each child they have will be born with AIS.

Types of AIS

There are 2 main types of AIS, which are determined by how much the body is able to use testosterone. These are:

  • complete androgen insensitivity syndrome (CAIS) – where testosterone has no effect on sexual development, so the genitals are entirely female
  • partial androgen insensitivity syndrome (PAIS) – where testosterone has some effect on sexual development, so the genitals are often not as expected for boys or girls

PAIS is usually noticed at birth because the genitals appear different.

CAIS can be more difficult to spot, as the genitals usually look like those of any other girl. It's often not diagnosed until puberty, when periods do not start and pubic and underarm hair does not develop.

Living with AIS

Children with AIS and their parents are supported by a team of specialists, who will offer ongoing care.

The team will help you understand your child's sex development. In the case of PAIS, they will talk to you about why they recommend raising your child as a boy or a girl.

Children with PAIS will be brought up either as girls or boys, depending mostly on the extent to which their body responds to hormones (androgens), including testosterone.

You and the specialist team will decide together what you think is in the best interests of your child.

Most children with CAIS are raised as girls.

Once you have learned about your child's sex development, and understand how their body will grow and develop, the specialist team can explain the treatment options your child might have in the future.

Support and advice

You and your child will be offered psychological support to help you understand and cope with the diagnosis of AIS.

Children may not need psychological support while they're very young. But they will need to grow up understanding their body and how it works.

You'll be given advice about talking to your child about AIS at all ages.

You may also find it helpful to get in touch with a support group, such as DSD Families.

Gender identity and gender dysphoria

Most children with AIS continue to feel they are the gender they grew up with.

In a few cases, older children and adults with AIS feel their gender identity does not match the gender they've been raised as. This is known as gender dysphoria.

People with gender dysphoria often have a desire to live as a member of the opposite sex or as non-binary.

They may want treatment to make their physical appearance more consistent with their gender identity or how they choose to identify.

If your child is diagnosed with AIS, you should be told about issues of gender identity.

National Congenital Anomaly and Rare Diseases Registration Service

If your child has AIS, your clinical team will pass information about them on to the National Congenital Anomaly and Rare Diseases Registration Service (NCARDRS).

The NCARDRS helps scientists look for better ways to prevent and treat AIS. You can opt out of the register at any time.

Symptoms

Babies with androgen insensitivity syndrome (AIS) will be genetically male, but will either have female genitals or an appearance between male and female genitalia.

There are 2 main types of AIS, which affect people in different ways:

  • complete androgen insensitivity (CAIS)
  • partial androgen insensitivity (PAIS)

Complete androgen insensitivity syndrome

CAIS isn't usually obvious from birth, as affected babies have female genitals – including a vagina and labia (folds of skin either side of the vaginal opening) – and are raised as girls.

They'll also have undescended testicles, but this will usually go unnoticed unless they cause a hernia (where they push through a weakness in the surrounding tissue) or swelling in the labia.

The first obvious symptoms often don't appear until puberty, which starts at around the age of 11 or 12.

When a girl with CAIS reaches puberty, she will:

  • not start having periods
  • develop little or no pubic and underarm hair
  • develop breasts and have growth spurts as normal, although she may end up slightly taller than usual for a girl

Girls with CAIS don't have a womb or ovaries, so are unable to get pregnant. Their vagina will also be shorter than normal, which may make having sex difficult.

Partial androgen insensitivity syndrome

The development of children with partial androgen insensitivity syndrome (PAIS) can vary.

In many cases, the genitalia are between male and female from birth. For example, affected babies may have:

  • a very small penis or an enlarged clitoris (the sexual organ that helps women reach sexual climax)
  • partially undescended testicles
  • hypospadias – where the hole through which urine passes out of the body is on the underside of the penis, rather than at the end

Children with PAIS are usually raised as boys, although they may experience poor penis development during puberty and develop small breasts. Most children with PAIS raised as boys will be infertile.

Some children with PAIS are raised as girls. Like those with CAIS, girls with PAIS don't have a womb or ovaries and won't be able to get pregnant.

Who can get it

Androgen insensitivity syndrome (AIS) is caused by a genetic fault that means the body can't respond to testosterone properly. The faulty gene is usually passed on to a child by their mother.

Testosterone is the male sex hormone produced by the testicles. It controls the development of the usual changes expected in boys, such as penis growth and the testicles moving into the scrotum.

How babies with AIS develop

In early pregnancy, all unborn babies have identical genitals. As they grow inside the womb, they develop either male or female genitals, depending on the pair of sex chromosomes they receive from their parents and their ability to respond to the sex hormones they make.

Sex chromosomes are bundles of genes – called X or Y – that play a vital role in a baby's sexual development. Females usually have 2 X chromosomes (XX), while males usually have an X and a Y chromosome (XY).

Children with AIS have male (XY) chromosomes, but the genetic fault they inherit prevents their body responding to the testosterone they make.

This means male sexual development doesn't happen as normal. The genitals appear female or between male and female, but a womb and ovaries don't develop internally.

How AIS is passed on

In most cases, the genetic fault is passed on to a child by their mother. The faulty gene is found on the mother's X chromosome.

As the mother has 2 X chromosomes, the normal chromosome is able to make up for the faulty one, so she's a carrier of the faulty gene, but doesn't have AIS and is able to have children.

Any genetically female (XX) children the mother has will also inherit 2 X chromosomes and will be unaffected, although they too may be carriers and be able to pass the genetic fault on to any children they have.

If the mother has a genetically male (XY) child, there's a chance they could pass on the faulty X chromosome, in addition to the Y chromosome the child gets from their father.

If this happens, the Y chromosome won't be able to make up for the faulty X chromosome and the baby will develop AIS.

This means women who carry the faulty X chromosome have a:

  • 1 in 4 chance of giving birth to a girl who's unaffected, but can pass on the altered gene to her children
  • 1 in 4 chance of having a boy who's unaffected
  • 1 in 4 chance of having a girl who's unaffected and doesn't carry the altered gene
  • 1 in 4 chance of having a child with AIS

This is known as X-linked inheritance.

Diagnosis

Androgen insensitivity syndrome (AIS) is sometimes diagnosed soon after a baby is born, although often it's not noticed until a child reaches puberty.

Doctors may suspect AIS based on a child's appearance and sexual development, but some tests will be needed to confirm the diagnosis.

Appearance and sexual development

Partial androgen insensitivity syndrome (PAIS) is usually spotted soon after birth because the genitals have an unusual appearance.

Complete androgen insensitivity syndrome (CAIS) isn't usually diagnosed at birth because the genitals look normal for a girl, but the condition may be picked up if the child gets a hernia.

Hernias are where an internal part of the body pushes through a weakness in the surrounding tissue. They can occur in babies with CAIS if the testicles fail to move from the tummy into the scrotum.

When the baby has an operation to repair the hernia, the surgeon may find the testicles inside the hernia or in the tummy, and tests may be arranged to check for CAIS.

If a baby with CAIS doesn't develop a hernia, the condition may go undiagnosed until puberty, when she doesn't start having periods and doesn't develop pubic and underarm hair.

Tests and scans

If AIS is suspected, blood tests can be used to:

  • check the sex chromosomes – sex chromosomes are bundles of genetic material that determine a person's genetic sex; if their genetic sex is different from their physical appearance, they may have AIS
  • check for a genetic fault – AIS is caused by a problem on the X chromosome, the sex chromosome a child with AIS receives from their mother
  • measure sex hormone levels – children with AIS tend to have high levels of testosterone (the male sex hormone) in their blood

An ultrasound scan can also be used to confirm the absence of the womb and ovaries. Children with AIS often have female genitals, but no female internal reproductive organs.

If a surgeon thinks they've found testicles in a baby's tummy during a hernia repair operation, a small tissue sample (biopsy) may be taken and analysed to confirm they are testicles and not ovaries.

Testing family members and unborn babies

If someone in your family has AIS and the specific genetic fault causing it has been identified, it may be possible to have a blood test to check if you carry the same fault and are at risk of passing it on to any children you have.

Testing can also be carried out in unborn babies when there's a known family history of AIS.

There are 2 main tests that can be carried out during pregnancy to determine whether a baby has the condition:

  • chorionic villus sampling (CVS) – a sample of cells are removed from the afterbirth (placenta) for testing, usually with a needle; this is usually carried out between week 11 and week 14 of pregnancy
  • amniocentesis – a needle is used to extract a sample of the fluid surrounding the baby (amniotic fluid) for testing; this is usually carried out between week 15 and week 20 of pregnancy

It can be difficult to decide whether or not to have these tests, so it's a good idea to speak to a genetic counsellor first.

It's also important to be aware that the risk of miscarriage after CVS and amniocentesis is estimated to be about 0.5 to 1%. This means 1 in every 100 to 200 women will have a miscarriage after having CVS or amniocentesis.

Living with

Children with androgen insensitivity syndrome (AIS) and their parents will be supported by a team of specialists who can offer ongoing information and care.

Various options are available to someone with AIS. Some are available in childhood, but most are offered in adolescence and adulthood.

Some people with AIS may want to discuss surgery and hormone therapy with their specialist team.

However, psychological support and advice is probably the most important part of care. This can help you understand your or your child's body and deal with any issues that arise as a result of AIS.

People with AIS lead full and satisfying lives and can maintain good health.

Gender identity

Gender identity is something that a person becomes aware of as they grow up. It's how they feel and how they show themselves to others when living as male, female or non-binary.

One of the aims of the specialist healthcare team involved with a baby with AIS is to advise parents about raising their child and their gender.

This is based on the team's estimation of how the child's physical sex development will continue with and without their help.

Parents play a big part in these discussions about babies. Older children and adults can take over discussions with doctors later.

Specialist healthcare teams advise that children with complete androgen insensitivity syndrome (CAIS) are raised as girls because they have female genitals, no testosterone response and almost always identify as female gender when they're older.

The decision is more difficult if a child has partial androgen insensitivity syndrome (PAIS).

A child's genitals may seem underdeveloped for a girl (short vagina). A boy may have a small penis with a hole at the base, not the tip.

You're entitled to specialist advice about your child's future development and any gender identity issues that could arise later.

Most children with PAIS stay with the gender they've been raised as. However, some people feel this does not represent who they are and decide to change gender in later life.

Talking to a child about AIS

Parents often wonder when and what they should say to their child about their AIS.

Many people feel it's best to help their child learn about how their body works as they grow up.

When any child learns about themselves and their bodies, it can be helpful for them to know from the earliest stage that people vary and difference is common.

Knowing this makes it easier to explain the basic facts about AIS as soon as possible.

They can then be given more detailed information as they get older, as their ability to understand increases.

It's recommended that a child fully understands their AIS before they reach puberty.

This can be a stressful time anyway, but just as adults try to prepare any child for changes that happen at puberty, a person with AIS needs to know what to expect their body to do.

It could be traumatic for a child to start puberty without knowing about the possible changes they may experience, or the differences between them and their friends.

When a girl with CAIS finds out about her AIS because her puberty is unusual, the healthcare professionals can explain and help her understand her body.

Support for parents

If a child is diagnosed with AIS, parents should be offered specialist counselling to help them understand their emotions.

A diagnosis of AIS can come as a surprise, and feelings of shame, guilt, anger and anxiety are common.

Talking to other families with AIS may also help. There are organisations that can put you in touch with other families, such as:

DSD Families
Contact helpline on 0808 808 3555

The DSD Families website also provides information and support for families affected by differences in sex development.

Support for children

Many young children with AIS do not need special psychological help because their condition is completely natural to them.

It can be good for children to know other children with AIS or similar conditions so that they do not grow up feeling alone or different from all other children.

However, as a child gets older, they may need support from someone with lots of understanding and experience in AIS to help them prepare for life with AIS.

A long-term relationship between the child and their specialist team is ideal so any new issues can be discussed as the child gets older.

Surgery

Children with PAIS will sometimes be offered surgery to help change their body and maintain their health.

People with CAIS will not be offered surgery until adolescence or adulthood.

Some procedures may be offered while a child is still young, but others can be delayed until they're older.

Hernia repair 

Children with AIS sometimes develop a hernia (where an internal part of the body pushes through a weakness in the surrounding tissue) soon after birth. This is a result of their testicles not moving from the tummy to the scrotum.

This can be repaired by closing and strengthening the gap created in the surrounding tissues. The testicles may also be removed during another operation.

Removing the testicles

Adults with CAIS will usually have their internal testicles removed. This is because there's a very small risk they could become cancerous if left in place throughout adulthood.

This procedure happens after puberty because the testicles produce hormones that help girls with CAIS develop a normal female body shape without hormone treatment.

Also, the risk of the testicles becoming cancerous before adulthood is extremely low.

If, for any reason, a child's testicles are removed before puberty, hormone treatment will be needed to keep them healthy and help them develop a more female body shape.

Surgery for boys with PAIS

Boys with PAIS may be born with fully or partially undescended testicles. If this happens, an operation can be carried out to move the testicles into the scrotum.

Read more about treating undescended testicles.

Surgery can also be used to straighten the penis and move the hole that carries urine out of the body to the end of the penis, rather than the underside.

Vaginal surgery

Girls with AIS often have a shorter vagina than most other girls and women, which can make penetration during sex difficult.

Treatment for this is usually delayed until after puberty, so that natural changes can take place.

Also, the young person can decide if she would like to know more about the treatment options.

The vagina can often be lengthened using a method called dilation. This involves inserting small plastic shapes that gradually widen and deepen the vagina.

Sometimes, a procedure to remove skin and tissue from the genital area and use it to surgically alter the vagina may be offered.

Some women with PAIS may want to discuss surgery to reduce the size of their clitoris. This may make it less sensitive and affect the ability to have an orgasm.

Male breast reduction

Boys with PAIS will sometimes have some breast development around puberty.

If this happens, talk to the specialist healthcare team, as breast reduction surgery may be offered. However, it's not usually available on the NHS.

Read more about male breast reductions.

Hormone therapy

Women with CAIS who have had their testicles removed will need to take oestrogen to prevent the menopause and osteoporosis.

Children with PAIS may need to take hormone supplements. Girls with PAIS who have their testicles removed may need oestrogen to encourage puberty.

This won't cause periods to start, as people with CAIS do not have a womb, but it will help them develop a more female body shape.

Hormone therapy will also be continued after puberty to stop people developing menopausal symptoms and weak bones (osteoporosis).

Boys with PAIS may be offered androgens (testosterone) to encourage certain male characteristics, such as facial hair and penis growth.



The information on this page has been adapted by NHS Wales from original content supplied by NHS UK NHS website nhs.uk
Last Updated: 13/06/2023 13:07:06