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Every hour of every day, a baby is born and can easily be identified as a boy or girl. But how distressing it must be when suddenly the birth attendants are unable to say whether the baby is a boy or a girl? This rare situation is usually unanticipated, and can be a difficult experience for all concerned. What causes this condition? What can be done? The following information has been developed to answer questions about ambiguous genitalia.

I have been told my baby has ambiguous genitalia and may have a disorder of sexual development (DSD). What does this mean?
Under normal circumstances, sexual development entails three basic steps. The first is the establishment of genetic or chromosomal sex at fertilization. This then determines the development of an undifferentiated gonad into a testis or ovary. The subsequent development of the internal reproductive ducts and external genitalia is due to production of hormone by the developed gonad. Interference with this developmental process at any step can result in a disorder of sexual development (DSD).

The medical term "intersex" is sometimes used to describe a number of well understood conditions which affect the formation of the genitalia early in embryonic development, often resulting in an appearance which is typical of neither a boy nor a girl. The precise underlying cause can usually be determined so that a recommendation can be made as to the appropriate gender in which to raise the baby. Surgery may also be offered so that the genitalia can look normal, like those of any other boy or girl.

A word of caution is necessary. DSD's are different than transexualism. Rather, we are concerned here only with a number of clearly defined disorders which, because of an altered hormonal environment affecting the fetus at an early stage of development, results in either overstimulation or under stimulation of the developing genitalia.

How do the genitalia normally form?
At the moment of conception, the mother imparts an X chromosome and the father an X or Y chromosome, creating either a female embryo with an XX or a male with an XY constitution. Despite this immediate definition of genetic sex, it is important to appreciate that male and female embryos are initially identical with respect to their internal and external genitalia. At this very early phase of development, embryos have two gonads, which have the ability to become either testes or ovaries. Every embryo also has both male and female internal genital structures that become the epididymis, vas and seminal vesicles in the male, and the fallopian tubes, uterus and upper vagina in the female.

The external genitalia of both male and female embryos at the six-week stage of development look identical. Very little adaptation is therefore required for the genitalia of girls to assume their definitive form. This process of sexual differentiation along a female pathway appears to be autonomous and is complete before the ovaries have fully formed.

For boys, however, a series of steps, beginning at about seven week’s gestation with the development of the testes, have to take place for the masculinizing process to proceed. The cells of the testes must first become organized and begin to produce testosterone, which is converted in the tissues of the genital region to a more powerful hormone calleddihydrotestosterone. This has to enter the nuclei of the genital cells to stimulate their growth causing the original slit-like groove to close over to form the urethra. The penis, which was initially the size of a clitoris, also enlarges and the mounds of tissue on either side of the midline expand to form the scrotum into which the testes eventually descend. At the same time, internal rudimentary structures known as mullerian ducts, which had the potential to form fallopian tubes and a uterus, wither away under the influence of another testicular hormone, known as mullerian inhibiting substance. All of these steps are virtually complete by the end of the first trimester, at which stage the external genitalia, apart from their size, look very much like those of a full-term baby boy.

What went wrong in the development of my baby's genitalia?
Although your baby's genitalia may look unusual, there is usually a very straightforward explanation as to how things developed the way they did. The problem can arise in babies of either sex, although the mechanisms are different.

For girls, who have a 46 XX genetic constitution, the external genitalia will be stimulated to enlarge if they are exposed to masculinizing hormones during the first few months of intrauterine life. Most commonly, these hormones are derived from the baby's own adrenal glands where, because of an enzyme defect, there is an overproduction of testosterone. This condition, known as congenital adrenal hyperplasia, is an inherited disorder that, if untreated, can be life-threatening because of an associated deficiency of cortisone and aldosterone, hormones which are essential for the maintenance of electrolytes and blood pressure. The key to treatment is to replace the missing cortisone and re-establish the hormonal balance. Replacement treatment will need to be lifelong and will initially be supervised by a pediatricendocrinologist.

Among other girls, the underlying reason for the masculinization of their genitalia may be that mother had an excess of masculinizing hormones in early pregnancy that passed across theplacenta. These may have come from some hormonal medication mother may have taken early in pregnancy or there may simply have been an imbalance in the hormones normally produced by her ovaries.

Irrespective of the underlying cause, the result on the genitalia of this excess of masculinizing hormones is a variable degree of enlargement of the clitoris and a tendency of the midline groove to close over so that the opening of the vagina becomes concealed. In spite of an often very masculinized appearance, the ovaries and uterus of such babies will always have developed normally.

Ambiguity of the external genitalia can also arise in a baby whose chromosomes are those of a normal male, namely 46 XY, or comprise a more complex pattern that usually includes a Y chromosome. Here, the underlying cause can usually be traced to a fault in one of the steps along the pathway of development in which the external genitalia of the early embryo normally become fully masculinized.

The underlying problem may be that the testes themselves failed to fully develop because of a gene defect in one or more of the chromosomes that are essential for their formation. Alternatively, one of the enzymes within the testes necessary for the production oftestosterone may be defective. Yet again, the testes may have formed properly and produced testosterone in adequate amounts but the external genitalia failed to respond as expected, either because of a deficiency of a specific enzyme they normally contain to convert testosterone to the more potent dihydrotestosterone. Finally, the cells of the genital tissues may have been incapable of responding to dihydrotestosterone because of a defect in their androgen receptor molecules necessary for triggering their enlargement.

As with the development of any organ in the body, the severity of the problem may vary widely. In some cases, the masculinizing process may have almost reached completion so that the penis is a good size but the urethral opening did not quite reach the tip of the glans, a condition called hypospadias. However, in other cases, development may have been arrested much earlier so that the penis remains small and tethered down with the urethral opening situated well back towards the scrotum. In the most severe cases, there may have been hardly any masculinization at all so that the external genitalia look very feminine.

What specific condition does my baby have?
Your baby is likely to have one of the following conditions, which is responsible for the appearance of the external genitalia. These are grouped according to the way in which the gonads developed.


In these conditions, the internal genitalia are female with two normal ovaries but the external genitalia are masculinized by an excess of male hormones. The following are the possible underlying causes:

  • Congenital adrenal hyperplasia: This common disorder is most often caused by a deficiency of the 21 hydroxylase enzyme: Rarely, it is the 11 b-hydroxylase or the 3 b-hydroxysteroid dehydrogenase enzymes which may be affected.
  • Placental aromatase deficiency: This is a rare enzyme defect in the placenta that leads to exposure of the fetus to an excess of testosterone.
  • Hormonal medications: If these are given in early pregnancy they sometimes have a mildly masculinizing effect on the fetal external genitalia.
  • Maternal hormonal imbalance.


In these conditions the external genitalia may be ambiguous but the gonads are recognizable as well formed testes. The underlying cause may be one of the following specific conditions:

  • Testosterone biosynthesis defect: In this condition there is a deficiency of one of the five enzymes normally found in the testis that are responsible for the formation of testosterone.
  • 5a-reductase deficiency: This enzyme, present in the cells of the male external genitalia, is essential for testosterone to exert its masculinizing effect, through conversion to DHT.
  • Partial androgen insensitivity syndrome: In this disorder all cells of the body are only partially responsive to the presence of testosterone.
  • Complete androgen insensitivity syndrome: In this disorder the cells of the body are totally unreceptive to the presence of testosterone so that the external genitalia remain completely female in appearance.

Disorders of Gonadal Differentiation

In these conditions the embryonic gonad fails to fully develop into a testis. Three varieties are recognized:

  • Mixed gonadal dysgenesis: In this condition one gonad remains at the undifferentiated stage of development while the other has formed a testis.
  • Partial gonadal dysgenesis: The gonads contain recognizable testicular tissue but this remains in a disorganized state and functions poorly.
  • Gonadal dysgenesis: In this condition both gonads remain in the undifferentiated phase of development.

Ovotesticular DSD

In this rare condition, the gonads comprise well organized ovarian and testicular tissue. Sometimes this results in an ovary on one side and a testis on the other. In most cases, however, each gonad contains a mixture of clearly identifiable ovarian and testicular elements.

How can the exact cause of my baby's problem be identified?
The necessary investigations to determine the underlying cause of your baby's problem include blood tests to examine the chromosomes and measure hormonal levels, an ultrasoundscan of the abdomen and pelvic area and a special X-ray examination, called a genitogram, to see if a vagina is present. In addition, it may sometimes be necessary to take a sample of tissue, known as a biopsy, from the gonads for examination under the microscope to be certain of their nature.

The chromosomes are most easily studied by examining lymphocytes, a type of white blood cell, which can be obtained from a small blood sample. Often, all that is necessary is a rapid and relatively inexpensive test to identify the two chromosomes. In other situations, though, a more detailed analysis, known as karotyping, is required, particularly when a 46 XY or a more unusual chromosomal pattern is suspected. The results of this may take three or four days to become known. Specific gene probe studies are now available in some research laboratories to aid in diagnosis. Although these are rarely necessary, they may sometimes be recommended in rare cases in which the underlying diagnosis remains unclear.

The detection of abnormally high or low hormone levels in the blood provides valuable information as to the nature of the underlying cause. For example, among babies withcongenital adrenal hyperplasia, by far the most common single cause of DSD, the levels of hormones above a suspected enzyme block will be abnormally high, whereas those below the block, for example cortisone, may be dangerously low. Once recognized, this imbalance can usually be rapidly corrected.

In other cases, the concentration in the blood of testosterone or mullerian inhibiting substance are measured to determine if there is any functioning testicular tissue present. These tests alone, however, are usually not diagnostic, although they provide helpful information in building up a picture of the underlying cause.

An ultrasound scan of the lower abdomen in girls with congenital adrenal hyperplasia will confirm the presence of a normal uterus and will often also show the upper portion of the vagina. In other conditions, such as mixed gonadal dysgenesis, a rudimentary uterus can sometimes be made out.

An ultrasound scan may also demonstrate the ovaries in girls with congenital adrenal hyperplasia, but although present, they are sometimes difficult to find. In other cases, when a gonad is felt in the groin or the pudendal region, an ultrasound scan will often give a clue as to its nature. However, when the findings are inconclusive, a biopsy will be necessary to be certain of the diagnosis.

In a special X-ray test called a genitogram, a radiologist passes a small catheter into the opening in the perineal region from which the urine is passed and injects some radio-opaque contrast material. The will demonstrate not only the urethra but will often also fill the vagina, if present, and reveal its size.

Among babies in whom the diagnosis of congenital adrenal hyperplasia has been confirmed from hormonal studies, the genitogram examination is concerned specifically with showing the level at which the vagina opens into the urethra. This information will be very helpful in planning the surgery necessary to bring the vagina out onto the skin. Among babies with other conditions, the genitogram may demonstrate internal duct structures such as a rudimentary uterine canal, fallopian tube or a vas.

In many cases, the all-important underlying diagnosis will already have been determined by the above tests. However, when doubt remains, the diagnosis will often hinge on the microscopic examination of some tissue taken from the gonads. This biopsy can be obtained either by laparoscopy or a mini-laparotomy, both of which will require a brief general anesthetic.

Once the underlying diagnosis is firmly established, the functional potential of the baby can be predicted with reasonable confidence with regard to what is likely to happen at puberty and the potential for fertility. This information, and a realistic appreciation of the ability of the external genitalia to function adequately, provide a basis for making a recommendation as to the optimal gender.

Can corrective surgery be done?
Surgery may be offered so that the genitalia can look normal, like those of any other boy or girl. Nowadays, operations to correct masculinized female genitalia, when carried out by an experienced surgeon, are remarkably successful and often result in an appearance that is indistinguishable from that of a normal girl. Surgery is not always necessary, particularly among girls with congenital adrenal hyperplasia who are only slightly masculinized, as the clitorisoften becomes less prominent as treatment to correct the underlying hormonal imbalance begins to take effect. A concealed vagina, however, will invariably require surgery to bring its opening out onto the surface, typically within the first 12-18 months of life.

Surgeons are increasingly aware of the importance of girls retaining normal sexual function after genital surgery. Therefore, in cases in which the clitoris is greatly enlarged, necessitating removal of a portion of the erectile bodies to improve appearance, great care is taken to avoid injury to the sensory nerves and to preserve the blood supply to the corpora and glans. It must be acknowledged, however, that long-term follow-up studies to determine to what extent surgeons have been successful in achieving these objectives are presently few. It is well recognized that after vaginal surgery, there is a tendency for the newly created opening to narrow. This sometimes necessitates further surgery, although often, simple dilatations begun during the teenage years prior to any sexual activity are all that are required.

Surgery for boys with severe hypospadias is usually successful in converting a penis, which is short and tethered down with the urethral opening set well back towards the scrotum, into one that looks remarkably normal. Any separation of the scrotal sacs, which may be present, will usually be corrected at the same time. The operation is usually carried out between six and 18 months of age and is accomplished in one or two stages. Once healed, the penis continues to grow in pace with the child's physical development and further surgery is only rarely needed. The structures necessary for sensation and erectile function are undisturbed by the surgery.

Other Frequently asked questions:

Will my child be able to produce children as an adult?
Girls with congenital adrenal hyperplasia can be regarded as potentially fertile once the underlying hormonal imbalance is corrected. Babies with other conditions must be evaluated on a case-by-case basis. Those with ovotesticular DSD with a functional ovary also have the potential to be fertile. Those with testicular dysgenesis, may have had their gonads removed because of the risk of tumor development but still have a well-developed uterus left in place that can potentially nurture an implanted embryo conceived in the laboratory using modern assisted reproductive techniques.

Boys having at least one testicle, which on biopsy is shown to be normal, have the potential to be fertile, although this is by no means certain. Paternity is often difficult to prove, but there are several confirmed instances among patients whose underlying problem was impaired production of testosterone or a defect of 5 alpha-reductase enzyme who have gone on to father children.

My baby has a Y chromosome. Does this mean he is a boy?
Not necessarily. It is important to appreciate that the role of the Y chromosome, or, more precisely, the SRY gene normally located on the Y chromosome, is simply to direct a cluster of cells, known as the indifferent gonad, to form a testis. To accomplish this, the SRY gene has to work in concert with other genes, any of which may be defective so that a true testis never forms. Even when the testis does form, masculinization of the developing embryo can only occur if all of the necessary subsequent steps reach completion. Thus, in spite of a Y chromosome, a breakdown of this stepwise process, for whatever reason, can leave the external genitalia looking very much, or in some cases even entirely, like that of a girl.

One can see, therefore, that the gender of the baby is something that is actually quite difficult to define. Practically speaking, what is much more important than the chromosomal constitution, is to think ahead as to what the future is likely to hold were any given baby to be raised as a male or, alternatively, raised as a female. To a large extent, this can be predicted once we have determined the precise underlying cause of the problem.

Will my baby have psychological problems down the road, particularly with regard to sexual preferences or gender identity?
Females with congenital adrenal hyperplasia and women with complete androgen insensitivity function remarkably normally in terms of gender identify and sexual function.

Among boys, the correction of even severe hypospadias should not compromise their ability to have satisfactory intercourse. Ejaculation, however, may be rather less forceful than normal, particularly when it was necessary to reconstruct much of the penile urethra.

We are on rather less certain ground when it comes to the long-term psychosexual outcomes for the rarer forms of DSD. In the past few years, we have become increasingly aware that testosterone, the hormone responsible for producing masculinization of the external genitalia, may also have an imprinting effect on the developing brain, potentially influencing gender identity. In essence, we have come to appreciate the brain as a "sex organ."

Further research is presently being undertaken to determine just how much weight should be given to such considerations when gender assignment of a baby with ambiguous genitalia is being considered. It is very important to remember that human sexuality is a highly complex subject and that the long-term psychosexual functioning of any individual, even those born with perfectly normal appearing genitalia, can never be predicted with certainty.

Posted: Feb 02, 2012