COMPLETE ANDROGEN INSENSITIVITY SYNDROME (CAIS)
CAIS is a rare inherited condition in which babies with male sex chromosomes
develop as girls because their bodies are unable to respond to androgens.
Androgens are the male hormones, chemical signals secreted into the blood
by the testes which are responsible for all the physical and psychological
features of maleness.
Inheritance.
CAIS is a genetic disorder carried on an X chromosome. Among the 23
pairs of human chromosomes there is one pair which control sexual development;
males have one X and one Y and develop testes whereas females have two
Xs and develop ovaries. An abnormal gene on one X chromosome can be compensated
by a normal gene on the other X, a condition caused by an abnormal gene
is therefore not expressed; this is called the ÔcarrierÕ state.
Without knowing it some women carry the abnormal gene for CAIS on one of
their X chromosomes and, since only one of each pair of chromosomes is
passed on to children, half their children will inherit this gene. If the
child has two X chromosomes (the other inherited from the father) she will
be a carrier like her mother but if the other sex chromosome is a Y there
is no compensating normal gene and the condition will be expressed.
Cause.
The abnormal gene for CAIS determines the structure of the androgen
receptor, a chemical in androgen-responsive cells which receives the messages
carried by androgens and starts the response of the cell. Babies with CAIS
have XY sex chromosomes and so develop testes and not ovaries. The testes
secrete normal male amounts of androgens but, because the structure of
the androgen receptor is abnormal, the cells of their bodies cannot "see"
the androgens and do not respond to them. Before birth androgens are responsible
for the development of male genitalia and after birth for all the other
features, physical and psychological, of maleness. In the absence of androgen,
or in CAIS the absence of androgen effect, babies develop into entirely
normal looking girls.
Diagnosis.
The diagnosis of CAIS is seldom made in babies because they look normal.
Occasionally small lumps in the groins are present and, when these are
removed or biopsied and examined under a microscope, they prove to be testes.
More commonly no suspicion arises until a girl fails to start her periods
and investigation reveals this condition.
Physical features.
Another separate function of the testes before birth is to suppress
the development of a womb and Fallopian tubes. This function is not determined
by androgens but by another hormone produced by the fetal testes called
MIF (Mullerian inhibitory factor). In CAIS the testes make MIF normally
and the cells respond to it. Girls with CAIS therefore lack not only ovaries
but also a womb and Fallopian tubes. Infertility is therefore inevitable.
The vagina is shorter than normal as the upper one third is not formed
but is usually adequate for normal intercourse. At puberty there is breast
development either in response to the small amount of female hormone secreted
from the testes if these are present or in response to oestrogen given
in treatment. There is little or no pubic and axillary hair, since these
are determined by androgens in both sexes. There is no inappropriate development
of male characteristics such as facial and body hair, muscularity and male
personality characteristics.
Treatment.
In girls with CAIS there is a very small chance that the testes may
eventually become cancerous; they are therefore removed surgically as soon
as convenient after the diagnosis is made (it used to be the recommended
practice to leave them until after puberty but it is now considered preferable
to remove them earlier although there is no cancer risk until adult life).
When the testes are removed treatment with oestrogen is necessary from
the age of puberty onwards to induce and maintain female development. This
can be done simply with a single daily tablet of oestrogen. Normal physical
and psychological female development is induced. Since they do not have
a womb affected girls do not have and do not need to have periods. Occasionally
the vagina may need surgical lengthening.
Outlook.
In spite of the fundamental problem in development, girls with CAIS
are fully fit and have a normal life span. They have normal intelligence
and psychologically they are normal females. They do not have any confusion
of sexual identity or orientation. Sexual and orgasmic function is normal
and there is no tendency to lesbianism or any sexual deviation. The only
major problems affected girls face are therefore, first, coming to terms
with the condition and secondly the very sad but relatively common problem
of infertility. This is obviously a difficult and potentially disturbing
condition to explain to affected girls but, as with all such conditions,
the best policy is nearly always honest and full explanation within the
limits of understanding of the child. However, some parents do still elect
to delay full discussion until their daughter reaches adult life. |
