Ambiguous genitalia

Definition

Ambiguous genitalia is a rare condition — usually obvious at or shortly after birth — in which an infant's external genitals don't appear to be clearly either male or female. In ambiguous genitalia, a baby's genitals may not be well formed, or the baby may have characteristics of both sexes. In a baby with ambiguous genitalia, the external sex organs may not match the internal sex organs.

Ambiguous genitalia can be very distressing for families. Your medical team will determine the cause of ambiguous genitalia and provide information and counseling that can help guide decisions about the baby's sex.

Symptoms

A newborn's genitals are quite small, and what looks "normal" spans a wide range. Your medical team will likely be the first to recognize the signs of ambiguous genitalia soon after your baby is born.

Ambiguous genitals may have various characteristics. Babies who are genetically female (with two X chromosomes) may have:

• An enlarged clitoris, which may resemble a small penis
• An opening where urine comes out (urethral opening) that's anywhere along, above or below the clitoris
• Closing together of the 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

Hypospadias

Hypospadias

Hypospadias is a condition in which the opening of the urethra is on the underside of the penis instead of at the tip. While the location of the opening can vary, it's usually near but underneath the ...

Causes

A baby's genetic sex is established at conception, based on the 23rd pair of 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. For example, the same fetal tissue that forms a penis in a male forms a clitoris in a female. The process by which the fetus becomes either male or female is complex and includes sex chromosomes, hormonal signals and early genital structures. In males, a region on the Y chromosome triggers the development of testicles, which produce male hormones. The presence or absence of male hormones controls the development of the sex organs. 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.

A disruption of these steps can result in a mismatch between the external genitals and the internal sex organs or the chromosomal sex (XX or XY). These problems are known as disorders of sex development (DSDs). Some babies with a DSD have ambiguous genitalia. 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.

Many different genes influence fetal sex development. Mutations (defects) in these genes can lead to disorders of sex development. Chromosomal abnormalities, such as a missing sex chromosome or an extra one, can also cause ambiguous genitalia. In some cases, disorders of sex development seem to happen by chance.

Possible causes in genetic females
Causes of ambiguous genitalia in a genetic female may include:

• Congenital adrenal hyperplasia (CAH). Certain forms of this genetic condition cause the adrenal glands to make excess male hormones (androgens). Congenital adrenal hyperplasia is the most common cause of disorders of sex development.
• Prenatal exposure to substances with male hormone activity. Certain drugs, including progesterone (taken in the early stages of pregnancy to stop bleeding) and anabolic steroids, can cause developing female genitals to become more masculine.
• Tumors. Rarely, a tumor in the fetus or 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.
• Congenital adrenal hyperplasia (CAH). Certain forms of this genetic condition can impair production of male hormones.
• Androgen insensitivity syndrome. In this condition, developing genital tissues don't respond normally to male hormones.
• 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.
• 5-alpha-reductase deficiency. This is an enzyme defect that impairs normal male hormone production.
• Prenatal exposure to substances with female hormone activity. If a woman continues taking birth control pills during pregnancy, the developing fetus can be exposed to the female hormone estrogen. Some drugs, including the anti-seizure medication phenytoin (Dilantin), can also have hormonal effects.

Risk factors

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

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.

Certain drugs with hormonal effects, including oral contraceptives, testosterone, anti-epileptic drugs and steroids, can also increase the risk of ambiguous genitalia. If the mother uses these substances during pregnancy, the developing fetus may be exposed to abnormal levels of hormones.

Complications

Many factors influence a person's gender identity. Families of babies born with ambiguous genitalia may need long-term support to help with ongoing issues regarding gender and sexuality. In the past, a baby born with ambiguous genitalia was quickly assigned a gender and surgery was performed to ensure the baby looked like a boy or girl. The newer approach encourages parents to allow children born with ambiguous genitalia to participate in decisions about their gender as they grow up.

The future sexual functioning and fertility of a baby born with ambiguous genitalia depends on the specific diagnosis. For example, genetic females with congenital adrenal hyperplasia usually can get pregnant if they so choose.

Some disorders of sex development are associated with an increased risk of cancer in sex organs or the liver.

Tests and diagnosis

If your baby is born with ambiguous genitalia, the first step is to determine the underlying cause of the disorder. This information helps guide treatment and decisions about the baby's gender. Because ambiguous genitalia is an uncommon and complex condition, you may be referred to a medical center with doctors who have expertise in disorders of sex development. The team might include a pediatrician, neonatologist, pediatric urologist, pediatric general surgeon, endocrinologist, geneticist, and psychologist or social worker.

Your doctor will likely begin by asking questions about your family and medical history and will do a physical exam to check for testes and evaluate the infant's genitalia.

Your medical team will likely recommend the following tests and procedures:

• Blood and urine tests to measure hormone levels
• Chromosome analysis to determine the genetic sex (XX or XY)
• Ultrasound of the pelvis and abdomen to check for undescended testes, uterus and vagina
• X-ray studies using a contrast dye to help clarify anatomy

If these tests don't provide enough information to establish a diagnosis, your doctor may use minimally invasive surgery (laparotomy or laparoscopy) to take a tissue sample (biopsy) of your newborn's reproductive organs. Specialized testing can provide more information about the cause of the sex disorder.

Assigning the sex
Using the information gathered from these tests, your doctor may suggest an appropriate sex for the baby. The suggestion will be based on the genetic sex, anatomy and future reproductive and sexual potential. Usually, a family can make a decision within a few days after the birth. Parents should be aware that as the child grows up, he or she may make a different decision about gender identification. You may want to consider giving the baby a gender-neutral first name.

Treatments and drugs

When treating ambiguous genitalia, the goals are to ensure long-term psychological and social well-being, sexual function, fertility, a gender-appropriate appearance and stable gender identity. The timing of treatment depends on a child's specific situation. Your medical team can explain the options available for your child and suggest a course of action.

Medications
Depending on the severity of the condition, hormone therapy may be enough to correct the initial hormonal imbalance. In a genetic female with a slightly enlarged clitoris caused by a minor to moderate case of congenital adrenal hyperplasia, proper levels of hormones may shrink the tissue close to a normal size.

Surgery
The goal of reconstructive surgery may be cosmetic, to make the genitals look natural. Surgery can also be done with the aim of preserving normal sexual functioning. Many doctors prefer to postpone surgery done for cosmetic reasons alone until the person with ambiguous genitalia is mature enough to participate in the decision about sex assignment.

For girls with ambiguous genitalia, the sex organs often work normally despite the ambiguous outward appearance. If a girl's vagina is hidden under her skin, surgery in childhood can help with sexual function later. For boys, surgery to reconstruct an incomplete penis can provide a natural appearance and erectile functionality.

Results of surgery are often satisfying, but repeat surgeries may be needed later. Risks include a disappointing cosmetic result or sexual dysfunction, such as an impaired ability to achieve orgasm.

Coping and support

Not knowing the sex of your newborn immediately can turn a hoped-for celebration into a stressful crisis. Until the medical evaluation is complete, you may have to avoid thinking of the child as either a boy or a girl. You may choose to defer formally announcing the birth until the testing is complete and you've come up with a plan with your medical team. You'll want to give yourself enough time to learn and think about the issue before answering questions from family and friends.

Mental health providers can help you deal with this difficult and unexpected set of circumstances. In addition to ongoing counseling for your family, you may benefit from a support group, either in person or online.