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

A child born with AIS is genetically male, but their genitals may appear to be female or somewhere in between male and female.

AIS is a very rare condition thought to occur in around 1 in every 20,000 births.

At an early stage of development in pregnancy, all unborn babies have identical genitals, regardless of whether they are male or female.

As a baby grows inside the womb, they develop either male or female genitals, depending on many factors including which pair of sex chromosomes they receive from their parents: XX or XY.

Sex chromosomes

Sex chromosomes are a pair of DNA molecules (X or Y) that play a vital role in a baby's sexual development. Females usually have two X chromosomes and males usually have one X and one Y chromosome.

The presence of a Y chromosome is important for the development of testes and prevents ovaries developing. If there is no Y chromosome, the female reproductive system and genitals will develop.

Read more about the male and female sex chromosomes.

What happens in AIS

The testes produce male hormones called androgens, which usually cause male sex organs, such as the penis, to develop. However, in AIS, the body ignores the androgen or is insensitive to it, so genitals develop along female lines and the testes usually remain inside the body.

Read more about the causes of AIS.

Types of AIS

There are two types of AIS, which are determined by the level of insensitivity to androgen. They are:

• complete androgen insensitivity syndrome (CAIS), where there is total insensitivity to androgen and a child develops external genitals that are entirely female; most children born with CAIS are brought up as girls
• partial androgen insensitivity syndrome (PAIS), where there is some sensitivity to androgen; the level of sensitivity will determine how the genitals develop

Depending on a person's level of insensitivity to androgen, they may look almost entirely male, entirely female, or have both male and female characteristics.

Children with PAIS can be brought up either as girls or boys, depending on the results of investigations and discussions with the specialist team after their birth.

Read more about the symptoms and grading system that is used for AIS.

Diagnosing AIS

Partial androgen insensitivity syndrome is usually diagnosed at birth because the genitals appear different.

Diagnosing complete androgen insensitivity syndrome can be more difficult because the genitalia usually look normal for a girl.

Many children with CAIS are diagnosed early in life when their testes cause hernias. When the hernias are operated on, the testes are discovered.

Otherwise the condition may not be diagnosed until puberty, when a girl's periods do not start and she has a lack of pubic and underarm hair. Breast development tends to be normal.

Read more about how AIS is diagnosed.

Treating AIS

A child with AIS should be offered psychological support if they need it. 

Counselling is not always needed in young children with AIS because their condition is entirely natural to them. However, counselling will be needed as the child gets older.

It is recommended that children with AIS fully understand their condition before they reach puberty, so that they are aware of the changes they may experience and the differences between them and their friends.

Children with PAIS may need to take hormone supplements. Girls with PAIS who have had their testes removed will need to take oestrogen to encourage female development during puberty and maintain secondary sexual characteristics in adulthood. It is not clear whether androgen supplementation is beneficial.

Boys with PAIS may need to take androgens (male sex hormones) to encourage certain male characteristics, such as the growth of facial hair and the deepening of their voice.

Women with CAIS who have gone through puberty and had their testes removed will need to take oestrogen to prevent them getting menopausal symptoms and developing weak bones (osteoporosis).

Read more about how AIS is treated.

Support

Most people with AIS are able to lead normal lives after receiving the appropriate care and support to help them come to terms with their condition. AIS does not reduce a person's life expectancy.

Support groups, such as the Androgen Insensitivity Syndrome Support Group (AISSG) and Differences of Sex Development (DSD families), provide help and support to young people, adults and families who are affected by AIS.

Most people born with the condition androgen insensitivity syndrome (AIS) will be infertile (unable to have children).

In most cases of AIS, development of the female reproductive organs is usually suppressed by a male sex hormone, which is produced by the testes (the male reproductive organs). Read more about what causes AIS.

This means that women with AIS do not have a womb, ovaries or fallopian tubes and are therefore unable to conceive. In men, only those with very mild AIS may be able to father a child. 

Complete androgen insensitivity syndrome

In about half of all babies born with complete androgen insensitivity syndrome (CAIS), their undescended (internal) testes cause a hernia, which brings the condition to light during infancy. Otherwise, there are no external physical signs of the condition during childhood.

The first obvious symptoms usually do not appear until puberty (average age of 11 for girls and 12 for boys, although it can be anywhere between 8 to 14) when the girl will:

• have little, or no, pubic and underarm hair
• not have acne (spots usually associated with puberty); acne is a reaction to the male sex hormone, androgen
• not start their periods due to the absence of ovaries (periods will usually occur by 14 to 15 years old)  

Also, the vagina of a woman with CAIS is usually about two-thirds the length of a normal vagina (6cm/2.4 inches). In some cases it may be even shorter.

Partial androgen insensitivity syndrome

The development of children with partial androgen insensitivity syndrome (PAIS) will depend on their level of insensitivity to androgen.

In some cases, babies with PAIS may be raised as boys but there is poor penile development during puberty. Some boys may show signs of breast development.

Hormone therapy can sometimes be used to optimise genital development.

Read more about how AIS is treated.

Androgen insensitivity syndrome (AIS) is caused by an alteration (mutation) in the gene that produces androgen receptors.

The male sex hormone, testosterone, cannot work properly until it locks onto an androgen receptor. Without enough androgen receptors, cells cannot react to androgen or the reaction is weaker than normal.

This means that testosterone does not cause the usual changes expected in boys, such as increasing penis size and pubic hair development.

For example, a person with complete androgen insensitivity syndrome (CAIS) will not react to testosterone at all and, as a result, the male genitals and reproductive organs will not develop and appear female.

In around a third of AIS cases, the androgen receptor gene becomes altered (mutates) for the first time during the formation of the mother's eggs, or in one of the embryo cells just after conception. The reasons for this are unclear.

In the remaining cases, the baby inherits the altered gene from their mother's X chromosome. In these cases, the mother is a carrier of the faulty gene and is unaffected.

Genetic inheritance

A female child will receive two X chromosomes; one from her mother and one from her father. If one of these X chromosomes carries the altered gene, the other X chromosome will balance out its effects and she will develop normally but be a carrier.

This means that if she has a baby, the baby has a chance of inheriting one altered X chromosome and one Y chromosome. The Y chromosome will not be able to balance out the effect of the alteration and the baby will develop AIS.

If a woman is a carrier of one altered X chromosome she has a:

• 1 in 4 chance of giving birth to a girl who is unaffected, but can pass on the altered gene to her children (altered X and normal X)
• 1 in 4 chance of having a boy who is unaffected (normal X and normal Y)
• 1 in 4 chance of having a girl who is unaffected and does not carry the altered gene (normal X and normal X)
• 1 in 4 chance of having a child with AIS (altered X and normal Y)

Read more about genetic inheritance.

Partial androgen insensitivity syndrome (PAIS) can usually be diagnosed at birth because the genitals are visibly different. Complete androgen insensitivity syndrome (CAIS) is often not diagnosed at birth and is recognised later.

Many children with CAIS are diagnosed early in life when their testes cause hernias.

A hernia is where an internal part of the body, such as an organ, pushes through a weakness in the muscle or surrounding tissue wall. When the hernias are operated on, the testes are discovered coincidentally and CAIS is diagnosed.

If a girl with CAIS does not develop a hernia, the condition may not be diagnosed until puberty, when her periods do not start and a lack of pubic and underarm hair becomes apparent. Breast development will be normal in these girls as the high testosterone level is converted to oestrogen.

Tests and scans

If androgen insensitivity syndrome is suspected, blood tests can be used to measure the person's sex hormone levels.

An ultrasound scan can also be carried out to confirm the absence of female internal reproductive organs. Ultrasound scans use high frequency sound waves to create images of the inside of the body.

Before birth

Unborn babies are not routinely tested for AIS because the condition is very rare. Pre-natal tests are often used in cases where there is a known family history of the condition.

It can sometimes be difficult to decide whether or not to have certain tests during pregnancy and in some cases genetic counselling may be necessary.

If the alteration (mutation) in the gene that produces the androgen receptors has been identified, AIS can be diagnosed after week 11 of the pregnancy.

This can be done using a procedure called chorionic villus sampling (CVS), which involves taking a sample of cells from the placenta (afterbirth) for testing.

Alternatively, amniocentesis can be used from week 15 of the pregnancy. This is where a needle is used to extract a sample of amniotic fluid so that it can be tested for genetic conditions and abnormalities. Amniotic fluid is the protective fluid that surrounds the developing baby in the womb.

Read more about chorionic villus sampling and amniocentesis.

Individuals with AIS are looked after by a specialist team usually led by a consultant paediatric endocrinologist.

Various treatment options are available to someone with AIS, including genital reconstructive surgery and hormone therapy. However, psychological support is probably the most important aspect of care.

As children with complete androgen insensitivity syndrome (CAIS) have female genitals, they are usually raised as girls.

For children with partial androgen insensitivity syndrome (PAIS), the decision can be more difficult, particularly if the genitals have both significant male and female characteristics. The specialist team together with the child's parents will help with this decision.

If your child has PAIS, you are entitled to receive advice from medical specialists and psychologists about your child's future development and the gender they are most likely to identify with. This is accessed through the regional specialist team (disorder of sex development team).

Most children with PAIS stay with the gender they are assigned as a baby. However, some decide this does not represent who they are and change their gender in later life.

Genital reconstructive surgery

Some children with PAIS need reconstructive surgery on their genitals. Surgery is not usually carried out before the child is one year old. The specialist team will advise parents about the optimum time of surgery for their child.

Removal of the testes

Girls with CAIS usually have their internal testes removed by early adulthood because there is small risk (less than 5%) of a tumour developing, which could become cancerous.

The operation to remove the testes, known as an orchidectomy, used to be carried out at an early age, but many experts now recommend leaving the operation until the girl has finished puberty (sexual maturation).

This is because the testes can help convert androgen to oestrogen, so the girl can develop a normal female body without need of hormone treatments.

Boys with PAIS can have surgery to move their testes into their scrotum (orchiopexy), and to straighten their penis so they can urinate standing up (hypospadias repair).

Vaginal lengthening

Some women with AIS decide to have vaginal-lengthening procedures to make sexual intercourse easier.

In the past, this was carried out before puberty, but doctors now usually recommend waiting until after puberty. This allows the woman to decide whether she wants the procedure and which particular procedure to have.

The vagina can be lengthened using a method called dilation, which involves gradually widening and deepening the vagina using small plastic rods. Another option is a procedure called a vaginoplasty. Women with PAIS can also have surgery to reduce their clitoris and enlarge their vaginal opening. The operation may make the clitoris less sensitive but achieving an orgasm should still be possible.

Hormone therapy

Women with CAIS who have been through puberty and had their testes removed will need to take a supplement of the female sex hormone, oestrogen. This will prevent them developing menopausal symptoms and weak bones (osteoporosis).

Women with CAIS tend to be tall because their male Y chromosome carries genes for extra height. Oestrogen can also be used to help regulate the growth of the woman's bones during puberty and prevent them growing excessively tall.

If the testes are removed during infancy or childhood, hormone treatment is usually started at 10 or 11 years of age to initiate female development during the child's puberty.

Children with PAIS may also need to take hormone supplements. Girls with PAIS who have their testes removed may need a combination of oestrogen and androgen to encourage puberty.

Boys with PAIS may need androgen to encourage certain male characteristics, such as the growth of facial hair or deepening of the voice.

Psychological support

Psychological support is probably the most important aspect of care, both for someone with AIS and their parents.

If your child is diagnosed with AIS, you should be offered psychological counselling. A diagnosis of AIS can often come as a shock to parents and feelings of shame, guilt, anger and anxiety are common.

Counselling can help you come to terms with your feelings. Talking to other parents who have a child with AIS may also help.

There are organisations that can put you in touch with other people affected by AIS. You can email the AIS Support Group (AISSG) at uk@aissg.org or call the Contact a Family freephone helpline on 0808 808 3555.

Sometimes, young children with AIS do not need psychological support because their condition is natural to them.

Parents often wonder when and what they should say to their child about their condition. Many people feel it best to explain the basic facts about the condition to the child as soon as possible. They can then be given more detailed information as they get older and their ability to understand increases.

It is recommended that a child fully understands their condition before reaching puberty. Puberty can be a stressful time and if your child starts puberty without knowing about possible changes they may experience, or the differences between them and their friends, they could find it traumatic.

As a child gets older, they may need psychological support from a therapist who has experience in AIS. A long-term relationship between the child and therapist is recommended so any new issues can be discussed as the child matures.

If CAIS is not diagnosed before a girl has started puberty, it may be difficult for her and her parents. Both should be offered psychological counselling, as well as appointments with a gynaecologist and an endocrinologist (hormone specialist).

In most cases, people with AIS are able to lead normal lives after receiving appropriate care and support to help them come to terms with their condition.