Disorders of Sexual Development (Pediatric)

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Conditions noted in this section are:

  • ambiguous genitalia
  • hypospadias
  • cryptorchidsm / undescended testes
  • testicular torsion
  • micropenis

Ambiguous Genitalia

What is ambiguous genitalia?

The diagnosis of ambiguous genitalia occurs when the external genitals do not appear clearly as male or female, calling into question the child's gender. This condition can be traumatizing for parents.

Early in fetal development, the tissue that becomes the gonads is undifferentiated and has potential to form either ovaries or testes depending on genetics. Humans have 46 chromosomes in each cell of their body (23 pairs). The 23rd pair determines gender. Females have two X chromosomes, while males have one X and one Y chromosome. This chromosome complement is referred to as "46, XX, normal female" or "46, XY, normal male."

There is another gene—SRY—located on the short arm (top half) of the Y chromosome. When SRY is present, the result is a male development. This gene causes the undifferentiated gonad to become testes around the sixth 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 seventh to eighth months of pregnancy, the testes descend into the scrotum.

The absence of the SRY gene results in a female development. The gonad differentiates into an ovary and the female reproductive tract continues to develop, forming the uterus and fallopian tubes. At the same time, regression of what would have been the male reproductive organs occurs.

Various genetic and environmental factors may influence this development and lead to ambiguous genitalia. Few infants with this condition have genitals so ambiguous that a gender determination cannot be made at birth. Far more common are these observations at delivery:

  • A female with severe virilizing (overproduction of male hormones) appears to have a small penis.
  • A male has an abnormally small penis resembling 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 and the most common ones are described below. In many cases, however, the cause is unknown. Children born with ambiguous genitalia may fall into one of the following groups:

Ovotesticular DSD

  • chromosomes that are either 46, XX or 46, XY or a mixture (referred to as "mosaic")
  • male and female internal reproductive organs
  • ovarian and testicular tissues
  • partially ambiguous external genitalia

Sex chromosome DSD

  • chromosomes that are 45, X or 46, XY or 46, XX or a mixture (referred to as "mosaic")
  • external genitals varying between normal female and male, with the majority female
  • internal sex organs that are usually female
  • undeveloped gonads

46 XY complete gonadal dysgenesis

  • female child has a 46, XY karyotype
  • female external genitalia
  • internal female reproductive organs
  • underdeveloped gonads

XX and XY DSD

Children have questionable external genitalia but only one gender's internal reproductive organs. The classification XY (gonads are testes) or XX (gonads are ovaries) DSD refers to the gonadal sex (the gender of the internal reproductive organs).

The primary causes of XY DSD are:

  • Androgen insensitivity syndrome occurs in children who have a 46, XY karyotype and normal female external genitalia. This condition is called androgen insensitivity syndrome because male infants are unresponsive 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 of having a son with androgen insensitivity syndrome, while daughters of mothers with the gene have a 50/50 chance of carrying the gene.
  • 5-alpha-reductase deficiency occurs in children who have a 46, XY karyotype and genital ambiguity. The enzyme 5-alpha reductase is deficient and cannot carry out its task of converting testosterone into dihydrotestosterone (DHT), which is necessary for complete masculinization of the external genitalia in a male fetus. A 5-alpha-reductase deficiency is inherited by an autosomal recessive gene, with each parent carrying one copy of the gene and transmitting it to their child. Carrier parents have a 1 in 8 or 12.5 percent chance per pregnancy to have an affected child (only males are affected).

There are many causes of XX DSD, most notably:

  • Congenital adrenal hyperplasia (CAH) is a defect in the enzyme 21-hydroxylase found in the steroid hormone synthesis pathway in the adrenal gland. CAH is most common in newborns—it's present in about 1 in 15,000 newborns and inherited by an autosomal recessive gene—and causes females to be masculinized. Autosomal recessive means that each parent carries one copy of the gene and transmits the gene at the same time to their child. Carrier parents have a 1 in 4 or 25 percent chance with each pregnancy of having an affected child. Affected females have ambiguous genitalia, while affected males do not. In some cases, the mother carrying a female child with CAH can be given medications during pregnancy to lessen the effects of the enzyme deficiency.
  • "Salt-wasting" CAH is another type of congenital adrenal hyperplasia that is serious and often lethal if not diagnosed, leading to an electrolyte collapse in the newborn. Treatment is available with early diagnosis. Males and females are equally affected. There are also other, more rare enzyme problems that result in CAH in males or females.
  • Overproduction of male hormones before birth is often due to adrenal gland abnormality (as described in CAH), yet it also results when high levels of male hormones enter the placenta or when the mother receives progesterone to prevent a miscarriage or has a hormone-producing tumor.

There are many other syndromes in which ambiguous genitalia is one feature of the disorder, in addition to other features.

How is the gender determined in a child with ambiguous genitalia?

When genitalia are ambiguous at birth, your child's doctor will conduct a medical history and physically examine the 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 doctor looks for an underlying cause of the disorder. Diagnostic procedures may include a newborn screening test for CAH, hormonal studies, and a biopsy of the reproductive organs. Children with ambiguous  are evaluated by a collaborative multidisciplinary team including pediatric urology, neonatology, genetics, pediatric endocrinology, and often psychiatry experts.  Our evaluation and decisions are determined as a team with strong input from families.

To determine the sex, your child's doctor may consider:

  • ability of an internal reproductive organ to produce appropriate sex hormones
  • actions of male or female hormones on the fetal brain
  • chromosomal analysis (to help determine genetic sex: 46, XX or 46, XY)
  • genitourethrogram to look at the urethra and vagina (if present)
  • pelvic ultrasound (to check for the presence of female reproductive organs)
  • risk of conditions (i.e., cancer) that may develop in the original reproductive organs later in life (children sometimes have an increased risk for tumors in the gonads)
  • size and potential for growth of a penis present in XY DSD
  • test to determine the fertility potential of a XX DSD
  • your opinion or preference

What is the treatment for ambiguous genitalia?

Treatment depends on the type of ambiguous genitalia and will usually include corrective surgery to preserve, remove and or create reproductive organs appropriate for your child's gender. Treatment may also include hormone replacement therapy (HRT).

What is the long-term outlook for children born with ambiguous genitalia?

Making a correct determination of gender is important for treatment purposes and for your child's emotional well-being. 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 such as difficulty or inability to conceive.

A small number of females are born with an abnormality known as "mullerian failure" or Mayer-Rokitansky syndrome. In these children, there is abnormal development of the vaginal opening, requiring vaginal replacement surgery. The technique for vaginal replacement developed by our doctors has been performed at NewYork-Presbyterian/Morgan Stanley Children's Hospital for the past 25 years. Our experience treating this type of abnormality is among the best in the world.