Symptoms

Your medical team will likely be the first to recognize ambiguous genitalia soon after your baby is born.

Babies who are genetically female (with two X chromosomes) may have:

• An enlarged clitoris, which may resemble a small 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

Causes

Ambiguous genitalia occurs when something goes wrong during pregnancy to interrupt or disturb the fetus' developing sex organs.

How sex organs form in the womb 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. Whether this tissue becomes male organs or female organs depends on the chromosomes. 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.

How ambiguous genitalia occurs A disruption of the steps that determine sex can result in a mismatch between the external genitals and the internal sex organs or the chromosomal 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 conditions may seem to happen by chance.

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 the male hormones in a pregnant woman can cause developing female genitals to become more masculine. Examples include progesterone, which is a medication sometimes taken in the early stages of pregnancy, and anabolic steroids. A developing baby may also 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.
• Congenital adrenal hyperplasia. 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.
• 5a-reductase deficiency. This enzyme defect impairs normal male hormone production.

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.

Complications

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.

Appointment

If your baby was born with ambiguous genitalia, you may be referred to a medical center with doctors who have expertise in this condition. Ambiguous genitalia is uncommon and complex and may require a team of experts. The team might include a pediatrician, neonatologist, pediatric urologist, pediatric general surgeon, endocrinologist, geneticist, and psychologist or social worker.

Because appointments can be brief, and because there's often a lot of ground to cover, it's a good idea to be well prepared. Here's some information to help you get ready and know what to expect from your doctor.

What you can do

• Be aware of any pre-appointment restrictions. At the time you make the appointment, be sure to ask if there's anything you need to do in advance, such as diet changes, to prepare your infant for tests and procedures.
• Write down key personal information, including family history of genetic diseases or conditions, such as ambiguous genitalia.
• Consider taking a family member or friend along. Sometimes it can be difficult to remember all the information provided during an appointment. Someone who accompanies you may remember something that you missed or forgot.
• Write down questions to ask your doctor.

Your time with your doctor is limited, so preparing a list of questions will help you make the most of your time together. List your questions from most important to least important in case time runs out. For ambiguous genitalia, some basic questions to ask your doctor include:

• What caused my infant's ambiguous genitalia?
• What kinds of tests does my infant need?
• What is the best course of action?
• What are the alternatives to the primary approach that you're suggesting?
• Are there any restrictions that my baby needs to follow?
• Should my infant see a specialist? What will that cost, and will my insurance cover it?
• Is there a generic alternative to the medicine you're prescribing?
• Are there brochures or other printed materials that I can take with me? What websites do you recommend?
• What will determine whether I should plan for a follow-up visit?

In addition to the questions that you've prepared to ask your doctor, don't hesitate to ask other questions during your appointment.

What to expect from your doctor Your doctor is likely to ask you a number of questions. Being ready to answer them may allow more time later to cover other points you want to address. Your doctor may ask:

• Does your family have a history of ambiguous genitalia?
• Does your family have a history of other genetic diseases?
• Do any diseases or conditions tend to run in your family?
• Have you ever had a miscarriage?
• Have you ever had a child who died in infancy?

Tests and diagnosis

Ambiguous genitalia is usually diagnosed at birth or shortly after. Doctors and nurses who help with your delivery may notice the signs of ambiguous genitalia in your newborn.

Determining the cause of ambiguous genitalia If your baby is born with ambiguous genitalia, the doctors will work to determine the underlying cause of the disorder. The cause helps guide treatment and decisions about the baby's gender. 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 tests to measure hormone levels
• Blood tests to analyze chromosomes and 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
• In certain cases, minimally invasive surgery may be necessary to collect a tissue sample of your newborn's reproductive organs

Determining the gender Using the information gathered from these tests, your doctor may suggest an appropriate gender 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.

Treatments and drugs

Once you and your doctor have chosen a gender for your baby, you may opt to begin treatment for ambiguous genitalia. The goal of treatment is to ensure sexual function and fertility, as well as long-term psychological and social well-being. When to begin treatment depends on your child's specific situation.

Medications Hormone medications may help correct the hormonal imbalance. In some children, hormones may be administered shortly after birth and may be the only treatment necessary. For example, 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. Other children may take hormones around the time they would normally undergo puberty.

Surgery In children with ambiguous genitalia, surgery may be used to:

• Preserve normal sexual function
• Create more natural-looking genitals

The timing of surgery for ambiguous genitalia will depend on your child's specific situation. Many doctors prefer to postpone surgery done solely for cosmetic reasons until the person with ambiguous genitalia is mature enough to participate in the decision about gender 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 may improve appearance and make erections possible.

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

If your baby is diagnosed with ambiguous genitalia, you may be worried for your child's future. Mental health providers can help you deal with this difficult and unexpected set of circumstances. Ask your child's doctor for a referral to a therapist or counselor who has experience helping people in your situation. In addition to ongoing counseling for your family, you may benefit from a support group, either in person or online.

Not knowing the gender 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.