Newborn males may present ambiguous genitalia as a very small penis mistaken for an enlarged clitoris, whereas newborn females may not have a vaginal opening.

Ambiguous genitalia also referred to as disorders of sexual development (DSD), is a very rare condition, in which you may find it difficult to determine the sex of the newborn by looking at the genitalia. 

• Newborn males with ambiguous genitalia have a very small penis that can be mistaken for an enlarged clitoris because the clitoris is usually big in newborn females. Sometimes, a penis may not have a urethral opening at the tip; instead, it is located under the penis.
• Newborn females with ambiguous genitalia may not have a vaginal opening.

The sex of the newborn with ambiguous genitals is determined with the chromosomal analysis.

A newborn can have characteristics of both genders. Ambiguous genitals are usually described as “intersex” in medicine. The sex of a baby with ambiguous genitalia is not determined readily, which may traumatize their parents. Sometimes, the newborn may be raised as the opposite sex, only to find their true sexuality at puberty.

How are genitals formed?

A baby inherits one set of sex chromosomes from each parent.

• A female baby has two X chromosomes (XX)—she inherits one X chromosome from her mother and one from her father.
• A male baby has one X chromosome inherited from his mother and one Y chromosome inherited from his father (XY).

The Y chromosome has a gene called SRY. When the developing fetus has XY chromosomes, the SRY gene halts the development of ovaries and other female reproductive systems to form the male reproductive system, and the baby is male.

In the absence of the SRY gene, the fetus proceeds with the development of the female reproductive system. However, along with the SRY gene, hormones in the uterus play an important role in the development of sex organs.

When a female fetus overproduces male hormones or is exposed to excess male hormones during development, her genitalia may appear like a small penis.

Due to insensitivity to male hormones or failure to produce male hormones, a developing male fetus may have an abnormally small penis that looks like a female clitoris.

External sex organs that develop in ambiguous genitalia give us the impression of sex of the infant that does not match with their chromosomes.

How to determine the sex of a baby with ambiguous genitalia

In most cases, the presence of disorders of sexual development (DSD) is obvious. However, in some cases, it is hard to diagnose DSD in a child, and you may know it only after the child reaches puberty.

The sex of the child may be determined by the following:

• Physical examination of external genitalia
• Abdominal ultrasound and magnetic resonance imaging to check for the internal reproductive organs
• Genitourethrogram to check for the urethra and vagina
• Chromosomal analysis to check for sex hormones—46XX is a female and 46XY is a male
• Reproductive tissue biopsy to determine the type of organ that is formed
• Assessment of sex hormones in the body

What are the causes of ambiguous genitalia?

Various factors influence the formation of ambiguous genitalia. However, in some cases, the exact cause of the disorder is unknown.

46 XX disorders of sexual development (DSD)

A condition of a female fetus in which their internal reproductive organs are of a female—she has a normal development of the ovaries, fallopian tube, and uterus—but external genitals look masculinized.

The condition may be caused by exposure to excess male hormones caused by following conditions:

1. Congenital adrenal hyperplasia:
   • The most common cause of DSD is which the clitoris grows very big and looks like a penis, and the vagina does not have an opening.
   • It is a condition in which the adrenal glands produce excess male hormones and low levels of cortisol.
   • This is a genetically inherited condition seen in 1 among 15,000 newborns; only affected newborn females have ambiguous genitalia, whereas newborn males who inherit the gene for this condition are not affected.
2. Hormonal therapy:
   • Sometimes, pregnant women may be given hormones to support their pregnancy if they have any hormonal imbalance.
   • However, this may lead to an increase in male hormones in the uterus, and the developing female fetus when exposed to these hormones may develop ambiguous genitalia.
3. Placental aromatase deficiency:
   • A rare condition in which there are very low levels of the enzyme aromatase. 
   • Aromatase deficiency causes a reduction in levels of the female sex hormone estrogen while increasing levels of the male sex hormone testosterone.
4. Maternal hormonal imbalance:
   • If the mother has a condition that leads to increased production of male hormones during her pregnancy, then this affects the development of the female fetus.

46 XY DSD

The male fetus develops male reproductive organs, but the size of the penis may be very small.

1. 5a-reductase deficiency:
   • 5a-reductase is an enzyme that converts testosterone to dihydrotestosterone (DHT).
   • DHT plays a role in the development of male sexual organs in the fetus. Deficiency of 5a-reductase leads to low levels of DHT.
   • This is a genetically inherited condition in which both male and female fetuses receive the gene responsible for this condition, but only males are affected.
2. Testosterone biosynthesis defect:
   • In this, the formation of the testosterone hormone is reduced due to the deficiency of certain enzymes that build testosterone.
3. Partial androgen insensitivity syndrome:
   • A genetically inherited condition in which some cells in the body fail to respond to male sex hormones.
4. Complete androgen insensitivity syndrome:
   • A genetically inherited condition in which the whole body fails to respond to male sex hormones, and external genitalia look like that of a female.

Disorders of gonadal differentiation

During the development of male reproductive organs, the testes may not develop completely, resulting in one of three types:

1. Mixed gonadal dysgenesis: One side of the testes is completely developed, whereas the other side stays premature.
2. Partial gonadal dysgenesis: The testicular tissue is formed but it is not completely developed, and the testes may not work properly.
3. Gonadal dysgenesis: Reproductive organs remain premature, and the testes are not formed.

Ovotesticular DSD

A very rare condition in which the fetus may have both male and female reproductive organs. In some cases, the fetus may develop an ovary over on one side and a testis on another side.

What are the treatment options for ambiguous genitalia?

Treatment of ambiguous genitalia differs according to the type of the condition but typically includes corrective surgery to remove or produce reproductive organs suitable for the child's gender. Hormone replacement therapy may be used in treatment.

There is an increased risk of the development of tumors in undescended testis. Hence, regular screening and removal of the testis may be required.