PARTIAL ANDROGEN INSENSITIVITY SYNDROME (PAIS)
PAIS is a rare inherited condition in which babies biologically 'intended'
to be boys fail to show full normal male development because their bodies
are unable to respond normally to male hormones, otherwise known as androgens
(these are the chemical signals secreted into the blood by the testes which
are responsible for all the physical and psychological features of maleness).
The cause of this condition and its implications are complex but in general
the outlook for affected people is much better than might be supposed.
Inheritance:
PAIS is a genetic disorder carried on an X chromosome. Among the 23
pairs chromosomes on which are carried all the genes which determine inheritance
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.
In genetic females an abnormal gene on one X chromosome can be compensated
by a normal gene on the other X. The condition caused by the abnormal gene
is therefore not expressed; this is called a ÔcarrierÕ state.
Without knowing it some women carry the abnormal gene for PAIS on one of
their X chromosomes and, since only one of each pair of chromosomes is
passed on to children, half their children 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 child will have PAIS.
Cause:
The abnormal gene for PAIS determines the structure or function 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 PAIS have XY sex chromosomes and so develop testes and not
ovaries. The testes secrete normal male amounts of androgens but, because
the androgen receptor is abnormal, the cells of their bodies cannot respond
normally. 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 full androgen effect, babies
have a variable degree of failure of masculinisation of their genitalia.
This can extend from an appearance almost indistinguishable from normal
female genitalia through a spectrum of abnormality to apparently normal
male genitalia apart from the fact that the urethra opens below the tip
of the penis (hyospadias).
Diagnosis:
The diagnosis of PAIS is usually made when a baby is investigated for
abnormality of the genitalia. The sex chromosomes prove to be XY and testes
are present which may be either undescended or in the scrotum.
Physical features:
A 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 MIH (Mullerian
inhibitory hormone). In PAIS the testes make MIH normally and the cells
respond to it. Babies with PAIS who resemble females therefore lack not
only ovaries but also a womb and Fallopian tubes, vaginal development is
variable. At puberty development is variable depending on the degree of
androgen resistance. If the testes are still present breasts may develop
in response to the small amount of oestrogen secreted by the testes but
there is usually little or no pubic and axillary hair, since these are
determined by androgens in both sexes, and no male characteristics such
as facial and body hair, muscularity and male personality characteristics.
Treatment:
In children with PAIS the decision on sex of rearing depends largely
on the external genitalia. If these are sufficiently masculinised to permit
sexual intercourse in the male role the baby can be brought up in the male
sex but if not the baby is brought up in the female sex and will require
external genital and sometimes vaginal surgery to a give normal female
genital appearance and function. In PAIS there is a chance that the testes
may eventually become cancerous; they should therefore be removed surgically
as soon as convenient after the diagnosis is made . When the testes are
removed treatment with testosterone for males or oestrogen for females
is necessary from the age of puberty onwards to induce and maintain male
or female development. Since they do not have a womb children brought up
as girls are inevitably infertile.
Outlook:
In spite of this fundamental problem in development, children with PAIS
are fully fit and have a normal life span. They have normal intelligence
and psychologically they fit well into the sex of rearing whether it is
male or female. As long as an appropriate decision is made early such children
do not have any confusion of sexual role or function and there is no tendency
to sexual deviation. This is a difficult and potentially disturbing condition
to explain to affected girls and some parents elect to delay full discussion
until adult life. |
