Ambiguous (Atypical) Genitalia: Born Without Developed Sex Organs

Ambiguous Genitalia

A rare condition, Ambiguous Genitalia, is a condition where the newborn’s gender is unclear. In other words, there is no clarity whether the newborn’s external genitalia is that of a male or a female.

In an infant with ambiguous genitalia, the external genitalia is either underdeveloped or has characteristics of both the genders. The child’s external sex organs might not match with the internal reproductive organs.

Is Ambiguous Genitalia a Disease?

The short answer is NO.

While Ambiguous Genitalia is not a disease, It is a disorder of sex development (DSD). Ambiguous genitalia usually show up at birth or shortly after that. Though not life-threatening, it can result in emotional distress in families. The medical team will look at the causes, counsel the parent, and guide on taking any decision about necessary treatments.

In Detail

The development of sex organs takes place in three basic steps. If anything goes wrong at any stage, then the fetus develops a DSD (developmental disorder). The primary reason for DSD is said to be hormones due to which the genitalia can end up growing abnormally and end up having features of both genders.

premature baby girl with Ambiguous Genitalia
Premature baby girl with Ambiguous Genitalia

It should be noted that while DSD refers to the inability of proceeding through sex determination as well as differentiation in standard fashion, not all infants with DSD end up with ambiguous genitalia. It is also not similar to transsexualism. A person is called transsexual if they physically transition from their defined gender to another gender.

How Sex Organs Develop

To understand the term ambiguous genitalia better, lets look at how sex organs are developed. The development of sex organs in a human fetus happens in three basic steps.

1. Determination of genetic sex

A newborn’s genetic sex is determined when the egg is fertilized with the sperm. If the fetus gets XX chromosomes, then it’s a girl. If the fetus gets XY chromosomes, then a baby boy is on the way.

2. Gonadal formation

The next step involves the creation of gonads or sex glands into ovaries in a girl or testes in a boy.

3. Development of internal reproductive system as well as outer genitals

The third step in genitalia formation is the development of the internal reproductive system. The hormones secreted from either ovaries or testes shape the fetus’s external genitals.

At the conception stage, the father shares either the X or Y chromosome and the mother an X chromosome. The chromosomes combine to form either XY pair (male embryo) or XX pair (female fetus). At the conception stage, there is not much difference between the male and female embryos.

Both male and female embryos begin with two gonads. The hormones secreted from these helps in the formation of ovaries or testes. Each embryo starts with the inner genital structures of both females and males. These end up becoming either female or male reproductive structures.

In girls, there are not many changes required for the formation of reproductive structures. The vagina is formed right away, even before the creation of ovaries.

In boys, however, a few steps need to be completed before the reproductive structures are formed. The formation starts with the formation of testes. The testes cells then begin production of testosterone, the male hormone. This is followed by the production of DHT or dihydrotestosterone, which causes changes to the genital tissues.

DHT helps in the formation of urethra’s slit-like groove. The penis, which starts with the size of a clitoris, starts enlarging. The tissue present on either side starts forming into the scrotum. Once the scrotum is fully developed, the testes descends into the scrotal sac.

While the external genitalia is developed inside the body, the müllerian ducts start forming the inner sex organs. In girls, these end up becoming fallopian tubes, uterus, as well as uterine cervix. The superior portion of the vagina is also formed during this time. In a boy, the müllerian ducts disappear.

All these take place within the first three months of fetal development. After three months, the outer sex organs resemble a vagina or a penis.

Symptoms of Ambiguous Genitalia

Ambiguous genitalia or disorder of sex development has no apparent cause and might be passed down from either parent. The medical team recognizes the DSD soon after the child is born. Occasionally, this can be caught during the fetal development stage.

Symptoms of ambiguous genitalia in babies with XX chromosomes (genetically female) include:

  • An enlarged clitoris, resembling a penis
  • Closed labia, which contains features of the scrotum
  • Lumps which resembles testes
Symptoms of ambiguous genitalia in babies with one X and Y chromosomes (genetically male) include:

  • Hypospadias – A condition where the urethra does not extend till the penile tip
  • Abnormally small penis. The urethral opening is near the scrotum
  • Absence of either one or both testicles in the scrotum
  • Undescended testicles as well as empty scrotum

Causes of Ambiguous Genitalia

There are four basic DSDs. These are grouped based on the gonadal formation.

1. 46XX DSD

In 46XX, the inner sex organs are female, but the vagina feels masculine. This is a result of the presence of too many male hormones. Some common causes are:

  • Placental Aromatase Deficiency: A rare enzyme problem present in the placenta, which causes the fetus to have excess testosterone.
  • Congenital Adrenal Hyperplasia: This is a common DSD where there is the presence of excess male hormones. This causes the female’s external sex organs to enlarge. The clitoris might end up looking like a penis. It can also result in the vaginal opening not being correctly visible. The enzyme and hormone levels become off-balance, and the cortisol level becomes very low.
  • Maternal Hormonal Imbalance: Sometimes, the pregnant mother can have a hormonal imbalance, which results in the fetus having too much testosterone.
  • Hormonal Medications: Sometimes, pregnant females are given certain hormones during their pregnancy. This might end up masculinizing the fetus.

2. 46XY DSD

In 46XY, the gonads end up becoming testes, but the penis has an unclear appearance. This might be due to:

  • 5a-reductase deficiency: Low levels of the 5a-reductase enzyme. Present in male gonads, this enzyme is essential for the development of testosterone, necessary for the production of DHT.
  • Testosterone biosynthesis defect: Deficiency or absence of one of the five enzymes required for building testosterone.
  • Partial Androgen Insensitivity Syndrome: This arises when the body’s cells are partially responsive to testosterone.
  • Complete Androgen Insensitivity Syndrome: This occurs when the body’s cells are completely unresponsive testosterone. This results in the outer genitalia looking like a female.

3. Gonadal Differentiation Disorders

This happens when the gonads do not completely develop into testes. These disorders can be of three types:

  • Gonadal dysgenesis: In this, the gonads stay premature and do not develop into testes.
  • Partial Gonadal Dysgenesis: There is an incomplete formation of testicular tissue, resulting in testes not working correctly.
  • Mixed Gonadal Dysgenesis: Here, one gonad forms a testis while the other gonad remains premature.

Ovotesticular DSD

A rare case where the gonads end up with both testicular and ovarian tissues. Sometimes, the fetus might have a testis on one side and an ovary on the other.

Ambiguous (Atypical) Genitalia

Many times one can quickly determine whether the newborn has a gender problem. In some of the cases, the diagnosis may not be simple. A majority of the children are diagnosed at birth. However, there are instances where the DSD is not diagnosed until teenage.

To diagnose if the child has DSD, the doctor performs various tests. These include:

  • A physical examination of the newborn’s outer sex organs
  • Blood tests to determine the hormonal and chromosomes levels
  • MRI or ultrasound scans to examine the internal organs
  • A genitogram for viewing the inner sex organs. This can include using x-rays as well as catheterization of the opening present between the genitals and the anus. This helps in seeing the urethra as well as the size of the vagina (if present). A genitogram is useful for planning corrective surgery.
  • Use of a dye
  • Biopsy for testing the gonadal tissue
  • Gene probe study, in rare cases

Often, blood tests can help in determining the level of hormones. Once this is determined, the doctor will prescribe appropriate treatment.

A definite diagnosis helps in defining the sexual function as well as fertility. Also, it allows parents to know what can be expected during puberty.

Treatment of Ambiguous Genitalia

Treatment for ambiguous genitalia depends on the root cause of the problem. Most often, reconstructive surgery is the appropriate treatment. This involves removing or creating suitable sex organs. Surgery done by experienced surgeons can help the child have normal-looking sex organs, however function can be impaired in some severe cases. Doctors also prescribe hormone replacement therapy (HRT) as a part of the treatment approach.

Hormone therapy might be the only required treatment for girls having mild congenital adrenal hyperplasia. When the hormonal imbalance is addressed, the girl can lead a healthy life. If her vagina is blocked, then she will require surgery. This surgical procedure is usually done within the first year or 18 months of age.

While vaginal surgery is being performed, the doctors take care of the clitoral sensitivity. Their main aim is to protect the blood supply and the sensory nerves. Often, the initial opening is very thin. The girl could require more surgeries as she ages. She might also be prescribed exercises for sufficiently stretching the opening along the years.

Surgery is also recommended for boys suffering from severe hypospadias, which is a safe and successful surgery. Surgery can result in the formation of a longer and much freer and normal-looking penis. Any separations made to the scrotal sacs are also repaired simultaneously.

Surgery for hypospadias is conducted in either one or two stages between the sixth month and 18th month of life. Once healed, the pace of penile growth matches the normal physical growth. Having surgery does not result in loss of erection or loss of sensation.