Ambiguous genitalia is a rare condition in which an infant's external genitals don't appear to be clearly either male or female. In a baby with ambiguous genitalia, the genitals may be incompletely developed or the baby may have characteristics of both sexes. The external sex organs may not match the internal sex organs or genetic sex.
Ambiguous genitalia isn't a disease, it's a disorder of sex development. Usually, ambiguous genitalia is obvious at or shortly after birth, and it can be very distressing for families. Your medical team will look for the cause of ambiguous genitalia and provide information and counseling that can help guide decisions about your baby's gender and any necessary treatment.
Your medical team will likely be the first to recognize ambiguous genitalia soon after your baby is born. Occasionally, ambiguous genitalia may be suspected before birth (prenatally). Characteristics can vary in severity, depending on when during genital development the problem occurred and the cause of the disorder.
Babies who are genetically female (with two X chromosomes) may have:
- An enlarged clitoris, which may resemble a penis
- Closed labia, or labia that include folds and resemble a scrotum
- Lumps that feel like testes in the fused labia
Babies who are genetically male (with one X and one Y chromosome) may have:
- A condition in which the narrow tube that carries urine and semen (urethra) doesn't fully extend to the tip of the penis (hypospadias)
- An abnormally small penis with the urethral opening closer to the scrotum
- The absence of one or both testicles in what appears to be the scrotum
- Undescended testicles and an empty scrotum that has the appearance of a labia with or without a micropenis
Ambiguous genitalia primarily occurs when hormone abnormalities during pregnancy interrupt or disturb the fetus's developing sex organs.
How sex organs form in the womb
A baby's genetic sex is established at conception, based on the sex chromosomes. The mother's egg contains an X chromosome, and the father's sperm contains either an X or a Y chromosome. A baby who inherits the X chromosome from the father is a genetic female (two X chromosomes). A baby who inherits the Y chromosome from the father is a genetic male (one X and one Y chromosome).
Male and female sex organs develop from the same tissue. Whether this tissue becomes male organs or female organs depends on the chromosomes and the presence or absence of male hormones.
- In males, a region on the Y chromosome triggers the development of testicles, which produce male hormones. Male genitals develop in response to male hormones from the fetal testicles.
- In a fetus without a Y chromosome — without the effects of male hormones — the genitals develop as female.
Occasionally, a chromosomal abnormality may make determination of genetic sex complex.
How ambiguous genitalia occurs
A disruption of the steps that determine sex can result in a mismatch between the appearance of the external genitals and the internal sex organs or the genetic sex (XX or XY).
- A lack or deficiency of male hormones in a genetic male fetus can cause ambiguous genitalia, while exposure to male hormones during development results in ambiguous genitalia in a genetic female.
- Mutations in certain genes can influence fetal sex development and cause ambiguous genitalia.
- Chromosomal abnormalities, such as a missing sex chromosome or an extra one, also can cause ambiguous genitalia.
- In some cases, the cause of ambiguous genitalia may not be determined.
Possible causes in genetic females
Causes of ambiguous genitalia in a genetic female may include:
- Congenital adrenal hyperplasia. Certain forms of this genetic condition cause the adrenal glands to make excess male hormones (androgens).
- Prenatal exposure to male hormones. Certain drugs that contain male hormones or that stimulate production of male hormones in a pregnant woman can cause developing female genitals to become more masculine. A developing baby also may be exposed to excess male hormones if the mother has a disease or condition that causes hormone imbalance.
- Tumors. Rarely, a tumor in the mother can produce male hormones.
Possible causes in genetic males
Causes of ambiguous genitalia in a genetic male may include:
- Impaired testicle development. This may be due to genetic abnormalities or unknown causes.
- Androgen insensitivity syndrome. In this condition, developing genital tissues don't respond normally to male hormones made by the testes.
- Abnormalities with testes or testosterone. Various abnormalities can interfere with the testes' activity. This may include structural problems with the testes, problems with production of the male hormone testosterone or problems with cellular receptors that respond to testosterone.
- 5a-reductase deficiency. This enzyme defect impairs normal male hormone production.
Ambiguous genitalia can also be a feature of certain rare, complex syndromes that affect many organ systems.
Family history may play a role in the development of ambiguous genitalia, because many disorders of sex development result from genetic abnormalities that can be inherited. Possible risk factors for ambiguous genitalia include a family history of:
- Unexplained deaths in early infancy
- Infertility, absent menstrual periods or excess facial hair in females
- Genital abnormalities
- Abnormal physical development during puberty
- Congenital adrenal hyperplasia, a group of inherited genetic disorders that affect the adrenal glands
If your family has a history of these risk factors, consider seeking medical advice before trying to conceive. You may also benefit from genetic counseling.
Complications of ambiguous genitalia may include:
- Infertility. Whether people with ambiguous genitalia can have children depends on the specific diagnosis. For example, genetic females with congenital adrenal hyperplasia usually can get pregnant if they so choose.
- Increased risk of certain cancers. Some disorders of sex development are associated with an increased risk of certain types of cancer.