Causes of androgen insensitivity syndrome

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 sex hormone produced by the testicles. It controls the development of the usual changes expected in boys, such as penisgrowth 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 two X chromosomes (XX),while males usually have one X and one 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 faultis passed on to a child bytheir mother. The faulty gene is found on themother's X chromosome.

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

Anygenetically female (XX) children the mother has will alsoinherit two X chromosomes and will be unaffected, although they too may be carriers and be able to pass thegenetic fault on to any children they have.

If the motherhas a genetically male (XY)child, there's achance they could pass onthe faultyX chromosome, in addition tothe Y chromosome the childgets from their father.

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

This meanswomen who carry the faultyX chromosome have a:

• oneinfourchance ofgiving birth toa girl who is unaffected, but can pass on the altered gene to her children
• oneinfourchance of having a boy who is unaffected
• one infourchance of having a girl who is unaffected and doesn't carry the altered gene
• oneinfour chance of having a child with AIS

This is known as X-linked inheritance. Read about genetic inheritance for more information.