Androgen insensitivity syndrome (AIS) is caused by an alteration (mutation) in the gene that produces androgen receptors. The androgen hormone cannot work properly until it locks onto these receptor molecules. Without enough of these androgen receptors, cells cannot react to androgen, or the reaction is weaker than normal.
For example, a person with complete androgen insensitivity syndrome (CAIS) has no reaction to androgen and the male genitals and reproductive organs do not develop.
In around a third of AIS cases, the alteration to the androgen receptor gene occurs for the first time in the family either 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 other cases, the altered gene is inherited as part of the X chromosome from the mother, who is a carrier.
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 carries one altered X chromosome, during every pregnancy she has a:
- one-in-four chance of having a girl who is unaffected, but can pass on the altered gene to her children (altered X and normal X)
- one-in-four chance of having a normal boy (normal X and normal Y)
- one-in-four chance of having a girl who is unaffected and does not carry the altered gene (normal X and normal X)
- one-in-four chance of having a child with AIS (altered X and normal Y)
