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Ambiguous Genitalia
When a child's gender is in question at birth, because genitals may not
appear clearly male or female, the child is said to have ambiguous genitalia.
Ambiguous genitalia can be a traumatizing experience for parents.
What are ambiguous genitalia?
Early in fetal development, the tissue that will become the gonads (ovaries
or testes) is undifferentiated and has the potential to become either
ovaries or testes, depending on the genetics of the fetus. Humans have
46 chromosomes in each cell of their body, or 23 pairs. The 23rd pair
determines our gender; females have two X chromosomes, while males have
one X and one Y chromosome. The chromosome complement in humans is written:
46, XX, normal female or 46, XY, normal male.
There is a gene located on the short arm (top half) of the Y chromosome,
called "SRY," which, if present, will cause the undifferentiated
gonad to become testes (indicating a male) around the 6th week of fetal
life. At the same time, regression of what would have been the female
reproductive tract occurs. As the testes produce testosterone, the phallus
(penis), scrotum, and urethra form. Later, during the 7th to 8th month
of the pregnancy, the testes will descend into the scrotum.
In the absence of the SRY gene, the gonad will differentiate into an
ovary (indicating a female). Likewise, the female reproductive tract will
continue to develop, forming the uterus and fallopian tubes. At the same
time, regression of what would have become the male reproductive organs
occurs.
A variety of genetic and environmental factors may influence this development,
leading to ambiguous genitalia. Ambiguous genitalia, as the word implies,
may make determining the child's gender more difficult. Very few infants
with ambiguous genitalia have genitals that are so ambiguous that a gender
determination is not made at birth. Far more common are the following
observations at birth:
- a female with severe virilizing (overproduction of male hormones)
who appears to have a small penis
- a male with an abnormally small penis that resembles a female clitoris
(due to an insensitivity to male hormones or failure to produce male
hormones)
What causes ambiguous genitalia?
There are a number of different causes of ambiguous genitalia, with
the most common described below. The cause, in many cases, is not known
and the disorder appears to occur by chance. Children who are born with
ambiguous genitalia may fall into one of the following groups:
- True hermaphroditism - children who have:
- both ovarian and testicular tissues.
- both genders' internal reproductive organs.
- external genitalia that are partially ambiguous.
- chromosomes that are either 46, XX, 46, XY, or a mixture (referred
to as "mosaic").
- Gonadal dysgenesis - children who have:
- an undeveloped gonad.
- internal sex organs that are usually female.
- external genitals that may vary between normal female and normal
male, with the majority female.
- chromosomes that are 45, X, 46, XY, 46, XX, or a mixture (referred
to as "mosaic").
- Pure gonadal dysgenesis - a female child who has a 46, XY karyotype,
underdeveloped gonads, internal female reproductive organs and female
external genitalia.
- Pseudohermaphroditism - children who have questionable external
genitalia, but have only one gender's internal reproductive organs.
The term male (gonads are testes) or female (gonads are ovaries) pseudohermaphrodite
refers to the gonadal sex (the gender of the internal reproductive organs).
There are two primary causes of male pseudohermaphroditism:
- Androgen insensitivity syndrome - children who have:
- 46, XY karyotype.
- normal female external genitalia.
This is called "androgen insensitivity syndrome," because
male infants are not responsive to androgens (testosterone). Androgen
insensitivity syndrome is inherited by a defect in the androgen receptor
gene on the X chromosome, and the inheritance is therefore described
as "X-linked recessive." Mothers who carry the gene have
a 50/50 chance to have a son with androgen insensitivity syndrome,
while daughters (of mothers who carry the gene) have a 50/50 chance
to be carriers of the gene.
- 5-alpha-reductase deficiency - children who have:
- 46, XY karyotype.
- genital ambiguity.
The enzyme 5-alpha reductase is deficient, therefore, it cannot carry
out its task of converting testosterone into dihydrotestosterone (DHT)
which is necessary for complete masculinization of a male fetus. A
5-alpha-reductase deficiency is inherited by an autosomal recessive
gene, which means that each parent carries one copy of the gene, and
transmits it to the child. Carrier parents have a one in eight, or
12.5 percent, chance, with each pregnancy, to have an affected child
since only males are affected.
There are a number of causes of female pseudohermaphroditism:
- Congenital adrenal hyperplasia (CAH):
- is caused by a defect in an enzyme (21-hydroxylase) in the steroid
hormone synthesis pathway in the adrenal gland.
- is the most common cause of ambiguous genitalia in newborns.
- causes females to be masculinized due to a deficiency of the enzyme
21-hydroxylase.
- is present in about one in 15,000 newborns.
- is inherited by an autosomal recessive gene. Autosomal recessive
means that each parent carries one copy of the gene, and transmits
the gene at the same time to the child. Carrier parents have a one
in four, or 25 percent, chance, with each pregnancy, of having an
affected child. Affected females have ambiguous genitalia, but affected
males do not.
In some cases, the mother of a child with CAH can be given medications
during pregnancy to lessen the effects of the enzyme deficiency, if the
fetus is female.
Another type of CAH, called "salt-losing," is very serious
and often lethal due to an electrolyte collapse in the newborn. Treatment
is available if diagnosed early. Males and females are equally affected.
There are other, rarer enzyme problems, which can result in CAH, in either
males or females.
- Overproduction of male hormones before birth:
- is often due to adrenal gland abnormality (as described in CAH
above)
- high levels of male hormones may also enter the placenta via the
mother, such as when the mother receives progesterone to prevent
a miscarriage or has a hormone-producing tumor.
There are a number of other syndromes in which ambiguous genitalia is
one feature (characteristic) of the disorder, in addition to other features.
How is the gender determined in a child with ambiguous genitalia?
When a child's genitalia appear ambiguous at birth, your child's physician
will conduct both a medical history and a physical examination of your
child's external genitalia. The medical history will include the mother's
health during pregnancy, and a family history of any neonatal deaths or
genital abnormalities. First, your child's physician will make a diagnosis
of the underlying cause of the disorder. Diagnostic procedures may include
a newborn screening test for CAH, hormonal studies, and a biopsy of the
reproductive organs.
To determine the sex, your child's physicians will consider the following:
- a pelvic ultrasound (to check for the presence of female reproductive
organs)
- a genitourethrogram to look at the urethra and vagina if present
- a chromosomal analysis (to help determine genetic sex: 46, XX or 46,
XY)
- fertility potential of a female pseudohermaphrodite
- size and potential for growth of a penis present in a male pseudohermaphrodite
- ability of an internal reproductive organ to produce appropriate sex
hormones for the gender "assigned" to the child
- risk of future health conditions (i.e., cancer) that may develop in
the original reproductive organs later in life
- the actions of male or female hormones on the fetal brain
- your opinion or preference
Treatment for ambiguous genitalia:
Sometimes, there is an increased risk for tumors in the gonads. Treatment
for ambiguous genitalia depends of the type of the disorder, but will
usually include corrective surgery to remove or create reproductive organs
appropriate for the gender of the child. Treatment may also include hormone
replacement therapy (HRT).
Long-term outlook for children born with ambiguous genitalia:
Making a correct determination of gender is both important for treatment
purposes, as well as the emotional well-being of the child. Some children
born with ambiguous genitalia may have normal internal reproductive organs
that allow them to live normal, fertile lives. However, others may experience
reduced or absent fertility (difficulty or inability to conceive a child).
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