Testicular feminisation syndrome
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 between male and female.
AIS is a very rare condition thought to occur in around 1 in 20,000 births.
In early stage pregnancy, all unborn babies have identical genitals, regardless of their gender.
As a baby grows inside the womb, they develop either male or female genitals, depending on which pair of sex chromosomes they receive from their parents: XX or XY.
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's no Y chromosome, the female reproductive system and genitals will develop.
What happens in AIS
The testes produce male hormones called androgens, which usually cause male sex organs, such as the penis, to develop.
However, when a person has AIS, the body ignores the androgen or is insensitive to it. Genitals then develop along female lines, and the testes usually remain inside the body.
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) – when there is total insensitivity to androgen and a child develops external genitals that are entirely female; most children born with CAIS are raised 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; this is dependent on investigations and discussions carried out with the specialist team after their birth.
PAIS is usually diagnosed at birth because the genitals appear different.
Diagnosing CAIS can be more difficult because female genitalia usually looks normal.
Many children with CAIS are diagnosed early in life, when their testes cause hernias. The testes are discovered when the hernias are operated on.
In other cases, CAIS may not be diagnosed until puberty, when a girl's periods don't start and she has a lack of pubic and underarm hair. Breast development tends to be normal.
A child with AIS should be offered psychological support.
When a child with AIS is young, counselling isn't always needed because their condition is completely natural to them. However, counselling will be needed as the child gets older.
It's recommended that children with AIS fully understand their condition before they reach puberty, so they're 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've had their testes removed will need to take oestrogen (a female sex hormone), to encourage female development during puberty and maintain secondary sexual characteristics in adulthood. It's 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 facial hair growth and the deepening of their voice.
Women with CAIS who've gone through puberty and had their testes removed will need to take oestrogen, to prevent them getting menopausal symptoms and developing weak bones (osteoporosis).
Most people with AIS are able to lead normal lives after receiving the appropriate care and support. AIS doesn't reduce life expectancy.
Support groups, such as the Androgen Insensitivity Syndrome Support Group (AISSG) and DSD (Differences of Sex Development) families, provide help and support to young people, adults and families affected by AIS.
Symptoms of androgen insensitivity syndrome
Most people born with androgen insensitivity syndrome (AIS) are infertile (unable to have children).
In most cases, the development of female reproductive organs is usually suppressed by a male sex hormone, which is produced by the testes (the male reproductive organs).
This means that women with AIS don't 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
Around half of all babies born with complete androgen insensitivity syndrome (CAIS) have undescended (internal) testes that cause a hernia. This makes the condition obvious during infancy. Aside from this, there are no external physical signs during childhood.
The first obvious symptoms don't usually appear until puberty. Most girls begin puberty between the ages of 8 and 14, with 11 the average age. Puberty tends to start later and last longer in boys, beginning between the ages of 9 and 14, with 12 the average age.
When a girl with AIS reaches puberty she will:
have little or no pubic and underarm hair
not have acne (spots usually associated with puberty); acne is a reaction to androgens (a group of male hormones)
not start her periods because of the absence of a womb and ovaries (periods usually occur when a girl is 14-15 years old)
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 they will experience poor penile development during puberty. Some boys may also show signs of breast development.
Hormone therapy can sometimes be used to optimise genital development.
Causes of androgen insensitivity syndrome
Androgen insensitivity syndrome (AIS) is caused by a change (mutation) in the gene that produces androgen receptors.
Testosterone (a male sex hormone) can't work properly until it locks onto an androgen receptor. Without enough androgen receptors, cells either can't react to androgen or the reaction is weaker than normal.
This means testosterone doesn't cause the usual changes expected in boys, such as increasing penis size and pubic hair development.
For example, if a person with complete androgen insensitivity syndrome (CAIS) doesn't react to testosterone, the male genitals and reproductive organs won't develop; instead, they will 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 around two-thirds of cases, the baby inherits the altered gene from their mother's X chromosome. When this happens, the mother is a carrier of the faulty gene and is unaffected.
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 if she has a baby, the baby has a chance of inheriting one altered X chromosome and one Y chromosome. The Y chromosome won't be able to balance out 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 doesn't carry the altered gene (normal X and normal X)
1 in 4 chance of having a child with AIS (altered X and normal Y)
Sex chromosomes play a vital role in a baby's sexual development; females have two X chromosomes and males have one X and one Y chromosome
Diagnosing androgen insensitivity syndrome
Partial androgen insensitivity syndrome (PAIS) can usually be diagnosed at birth because the genitals are visibly different.
Complete androgen insensitivity syndrome (CAIS) isn't usually diagnosed at birth and is discovered 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 doesn't develop a hernia, the condition may go undiagnosed until puberty, when her periods don't start and a lack of pubic and underarm hair becomes apparent. Breast development will be normal in these girls, because the high level of testosterone (a male sex hormone) is converted to oestrogen (a female sex hormone).
Tests and scans
If AIS 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 (womb and ovaries). Ultrasound scans use high frequency sound waves to create images of the inside of the body.
Unborn babies aren't routinely tested for AIS because the condition is very rare. Pre-natal tests are often used in cases where there's a known family history of the condition.
It can sometimes be difficult to decide whether to have certain tests during pregnancy. In some cases, genetic counselling may be necessary.
If the change (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.
Individuals with AIS are looked after by a specialist team that's usually led by a consultant paediatric endocrinologist.
An endocrinologist is a doctor who specialises in the endocrine glands and the substances (hormones) they secrete. The endocrine glands include the:
ovaries and testes
part of the pancreas
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're 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 will work closely with the child's parents to help make this decision.
If your child has PAIS, you're entitled to receive advice from medical specialists and psychologists about your child's future development and the gender they're 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're assigned as a baby. However, some people feel this doesn't represent who they are and decide to switch gender in later life.
Some children with PAIS need reconstructive surgery on their genitals. Usually, the child needs to be at least one year old, but the specialist team will advise parents on the right time for surgery to take place
Removal of the testes
Girls with CAIS usually have their internal testes removed by early adulthood as there's a small risk (less than 5%) of a tumour developing, which could become cancerous.
The operation to remove the testes is known as a gonadectomy or orchidectomy. The procedure used to be performed at an early age, but many experts now recommend carrying it out after 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 needing hormone treatment.
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).
Some women with AIS decide to have their vagina lengthened, to make sexual intercourse easier.
In the past, this was carried out before puberty, but doctors now usually recommend waiting until after puberty. This means the woman can decide if she wants the procedure, and which one in particular 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 surgical procedure known as a vaginoplasty. It involves removing skin and tissue from the genital area and using it to reconstruct the vagina to improve its function and appearance.
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.
Women with CAIS who have been through puberty and had their testes removed will need to take a supplement of oestrogen (the female sex hormone). 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 bone growth during puberty and stop them becoming excessively tall.
If the testes are removed during infancy or childhood, hormone treatment is usually started at 10 or 11 years old, so that female development begins during 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 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 the condition. You can email the AIS Support Group (AISSG) at firstname.lastname@example.org, or call the Contact a Family freephone helpline on 0808 808 3555 FREE.
Sometimes, young children with AIS don't need psychological support because their condition is completely natural to them.
Parents often wonder when and what they should say to their child about their condition. Many people feel it's 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's recommended that a child fully understands their condition before reaching puberty. This can be a stressful time anyway, but if your child starts puberty without knowing the possible changes they may experience, or the differences between them and their friends, this could be traumatic.
As a child gets older, they may need psychological support from a therapist with experience in AIS. A long-term relationship between the child and therapist is recommended, so that any new issues can be discussed as the child matures.
If CAIS isn't diagnosed before a girl has started puberty, the situation may become difficult for both 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.
If testing has shown that you're a carrier of the altered X chromosome that can cause AIS, you may wish to have genetic counselling.
Genetic counselling will give you information about AIS, the effect it can have on your life and the options available to you in the future.
Testicular feminisation syndrome