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Causes

Androgen insensitivity syndrome (AIS) is caused by a genetic alteration that means the body cannot respond to testosterone either completely or partially.

Testosterone is the 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 down into the scrotum.

In early pregnancy, all unborn babies have identical genitals. As they grow inside the womb, they develop either male or female genitals. This depends 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 sex development. Females usually have 2 X chromosomes (XX), while males usually have an X and a Y chromosome (XY).

Children with AIS have XY chromosomes, but the genetic alteration they inherit prevents their body responding to testosterone (the sex hormone).

This means male sex development does not happen as normal. The genitals appear female or underdeveloped. A womb and ovaries also do not develop internally.

In most cases, the genetic alteration is passed along the female line to a child. The AIS 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. This means she's a carrier of the AIS gene, but does not 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. However, they too may be carriers and be able to pass the AIS gene on to any children they have.

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

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

This means women who carry the AIS-affected 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 does not carry the altered gene
  • 1 in 4 chance of having a child with AIS

This is known as X-linked inheritance.