Differences of sex development (DSD)

What are differences of sex development?

Before birth, sex development goes through several steps: the chromosomes (XX or XY), the formation of the sex glands (gonads: testicles or ovaries), and the development of the external genitals under the influence of hormones. When there is a difference at one of these steps, the chromosomes, the gonads and the genital anatomy may not fully match each other. These conditions are called differences of sex development, or DSD for short.

DSD is not a single condition but a group of conditions that differ widely in cause, appearance and course. Some need only hormone treatment; others need long-term follow-up.

Types

According to the international classification, DSD is divided into three main groups:

• Sex chromosome DSD: a difference in the number or structure of the sex chromosomes (for example, XY in some cells and X in others).
• 46,XY DSD: the chromosomes are XY, but the development of the testicles or the action of male hormones is incomplete.
• 46,XX DSD: the chromosomes are 46,XX and sex development differs. One cause is extra male hormone effect before birth, most often due to congenital adrenal hyperplasia (CAH), an inherited enzyme deficiency of the adrenal glands. Less often, the gonads develop differently.

How is it found?

During pregnancy

Sometimes the appearance of the genitals on prenatal ultrasound does not match the result of the baby’s genetic test. In such cases, genetic counseling before birth and an evaluation by an experienced team after birth are planned.

After birth

Signs that suggest a DSD:

In a baby who appears male:

• severe hypospadias with a split (bifid) scrotum,
• hypospadias together with one or both undescended testicles,
• in a full-term baby, neither testicle can be felt.

In a baby who appears female:

• enlargement of the clitoris of any degree,
• gonads that can be felt in the groin or in the labia,
• no separate openings for the urethra and vagina (a single opening).

Ambiguous genitalia: from the appearance, it is hard to say whether the baby is a boy or a girl.

Some forms are found later: for example, when a testicle is found during inguinal hernia surgery in a girl, when a teenage girl does not start having periods, or when unexpected changes appear during puberty.

Note: mild hypospadias, a single undescended testicle or a penis that looks small are, in most cases, not a DSD. More details: micropenis.

Why is it urgent in a newborn?

In some forms of CAH, the adrenal glands do not make enough of certain vital hormones. As a result, the body loses salt and fluid. This usually shows up in the first weeks as vomiting, poor feeding, weight loss and unusual sleepiness, and without timely treatment it is life-threatening. That is why every newborn with ambiguous genitalia should be evaluated right away.

Tests

The evaluation is done step by step, and the results are reviewed by the team:

• Family history: parents who are blood relatives, similar conditions in the family, infant deaths, absent periods or infertility in women in the family, exposure of the mother to male hormones during pregnancy.
• Examination: genital anatomy, the position of the urinary opening, whether the gonads can be felt and whether they are symmetric, skin color, blood pressure.
• Blood tests: electrolytes, 17-OH progesterone, cortisol, ACTH, LH, FSH, testosterone.
• Special urine test: when indicated, specialised urinary adrenal steroid testing.
• Genetic tests: karyotype and, when needed, a broader genetic panel or exome analysis.
• Ultrasound: to assess the internal reproductive organs (uterus, gonads) and the kidneys.
• Genitogram: a contrast X-ray study that shows the structure of the urethra and vagina.
• hCG stimulation test: checks whether the testicles can produce testosterone.
• When needed, endoscopy or laparoscopy under anesthesia.

How are decisions made?

A child with a DSD should be cared for by a multidisciplinary team at an experienced center: a neonatologist, pediatric endocrinologist, geneticist, pediatric urologist and psychologist, and later on, doctors who care for adults.

• Shared decisions: decisions about the sex in which the child is registered, about genital surgery and about the gonads are made together with the family, after an open discussion of all options, benefits and risks.
• Surgery: genital surgery is done in line with national regulations. There is no need to rush irreversible operations. In some cases they can be postponed until the child is old enough to take part in the decision.
• Gonads: removal of the gonads (gonadectomy) is considered only after multidisciplinary discussion. When gonads that have not developed typically contain Y-chromosome material, the risk of a tumor is higher. The family is fully informed about this, and the decision is made individually based on the level of risk.
• Psychological support: the effects of a DSD on psychological health, quality of life, relationships and sexual life should not be underestimated. Psychological support for the parents and the child should start from the time of diagnosis.

Treatment

Treatment depends on the cause:

• Hormone treatment: in CAH, the missing adrenal hormones are replaced for life. In some forms, sex hormone treatment may be needed at puberty.
• Surgery: when the team and the family decide on it together, surgery may include hypospadias repair (hypospadias repair), bringing the testicles down (orchiopexy) or other reconstructive operations.
• Observation: some children need no surgery at all, only regular follow-up.

Long-term follow-up: what to expect

• Regular follow-up with the endocrinologist and pediatric urologist, including assessment of puberty.
• Gradual, honest, age-appropriate information for the child about their condition.
• A separate conversation in adolescence about future sexual life and options for having children.
• Ongoing psychological support.
• A planned move to adult doctors during adolescence.

In many forms of DSD, with proper treatment and support, children go on to live healthy and full lives.

When to see a doctor

Seek care urgently if:

• a newborn has ambiguous genitalia,
• neither testicle can be felt in a full-term baby who looks like a boy,
• a newborn has hypospadias together with an undescended testicle,
• such a baby has vomiting, poor feeding, weight loss or unusual sleepiness.

Make a planned appointment if:

• an older boy has hypospadias together with an undescended testicle and has not been evaluated before,
• a girl has an enlarged clitoris, a swelling in the groin, or does not start having periods in adolescence.