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Causes and Treatment Of Ambiguous Genitalia in Indian Children

Q: Is surgery always necessary for children born with ambiguous genitalia?

No, surgery is not always necessary to correct ambiguous genitalia. Some babies could have conditions that pose a risk to their health and, therefore, require immediate surgery. In other cases, surgery may be done solely for cosmetic reasons and is not always viewed as essential.

Q: Is the sex assignment for persons with ambiguous genitalia always accurate?

In most cases, persons with ambiguous genitalia are happy with the sex that is assigned to them. However, in some cases, patients may be dissatisfied or discontent with the sex that has been assigned to them and may have a strong desire to change their bodies.

With inputs from Dr. Uma M - Consultant Family Physician, and Diabetologist

Updated on: November 2023

With inputs from Dr. Uma M - Consultant Family Physician, and Diabetologist

Updated on: November 2023

Reviewed by Dr Raja Indana

Read our editorial policy

Table of contents

‘Boy or Girl?’, that’s a question commonly posed to most new and/or soon-to-be parents in India, and it generally comes as no surprise! Much of the world around us today think of sex and gender in binary terms.As soon as a child is born, they are assigned either of the two biological sexes viz., male or female based on their genetic differences and genitalia. Throughout their lifetime, they are then gradually shaped to take on their respective gender roles.

Sounds pretty straightforward, right? But what happens when you cannot clearly tell if a child is a boy or a girl?

This can be a distressing experience for both families and/or people who struggle with questions related to sexual ambiguity.

Sexual ambiguity, or what is more widely termed as “ambiguous genitalia”, is a rare condition that is estimated to occur in as many as 1 in every 4500 infants that are born.

Yet, as a result of the rigid dimorphic sexual paradigm that exists in India and the world today, there is little or no public awareness about the condition. This has failed to adequately address, treat, and rehabilitate persons with the disorder and the societal stigma surrounding the condition has remained mostly unchanged over the years.

Increased awareness of differences in sex development (DSD) or more specifically, the condition called ambiguous genitalia is, therefore both necessary and important.

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Chapter 1: What is Ambiguous Genitalia?

Ambiguous genitalia is a congenital condition that is relatively uncommon or rare. In this condition, an infant’s reproductive organs and genitals appear to be atypical or look different from the usual.

Example:
Babies who are genetically female (with two X chromosomes) may have:

An enlarged clitoris, which may resemble a penis
Closed labia, or labia that include folds and resemble a scrotum
Lumps that feel like testes in the fused labia

Babies who are genetically male (with one X and one Y chromosome) may have:

A condition in which the narrow tube that carries urine and semen (urethra) doesn’t fully extend to the tip of the penis (hypospadias)
An abnormally small penis with the urethral opening closer to the scrotum
The absence of one or both testicles in what appears to be the scrotum
Undescended testicles and an empty scrotum that has the appearance of a labia with or without a micropenis

While this condition requires prompt evaluation, it is crucial to understand that it is not a disease.

Instead, it is simply viewed as a disorder or difference in sex development (DSD). In rare cases, however, it may constitute a medical emergency if it is a result of a genetic disorder called congenital adrenal hyperplasia.

The difference between ambiguous genitalia, intersex, and transgenderism

Many times, people also tend to use “ambiguous genitalia” interchangeably with the term “intersex”, while some occasionally confuse it with transgenderism. There are, however, important distinctions between the three conditions, and it is important to understand them.

“Intersex” is an umbrella term used for people who are born with hormonal, physical, or genetic disorder symptoms in their reproductive organs or sexual anatomy. This can cause them to have a combination of female and male hormones in their body or features that are neither wholly male nor wholly female.

What differentiates intersex people from ambiguous genitaled children or persons is the fact that not all intersex people are born with abnormal genitalia.

For example, some people may be born with external genitals that can be clearly classified as male or female. However, there may be a contrariety between their external genitals and their internal reproductive organs.

Intersex traits may also not always be immediately noticeable when a child is born. Some of these traits may only become apparent during early adolescence or even much later in their life.

“Transgenderism”, on the other hand, relates to a condition wherein a person cannot identify with the sex that was assigned to him or her at birth. For example, a person may identify as a man despite being born with female reproductive organs or female genitalia.

How does abnormal genitalia occur in babies?

In order to understand the occurrence of ambiguous genitals in newborns, it is crucial to first try and understand how a baby’s genitals develop during pregnancy. For that, let’s review some basics:

At around 18 to 22 weeks of pregnancy, a baby’s sex can be determined through a level 2 anatomy ultrasound.

This is an exciting moment for parents-to-be! But as you may already know, a baby’s sex is decided at the time of conception. When a baby is conceived, it receives two sex chromosomes: one from the mother and one from the father. There are different chromosomes for male and female. As the mother always has two X chromosomes, it is the father’s cells that determine if the child will be a boy or a girl. Two X chromosomes (XX) will make a girl, while a boy will make X chromosome and Y chromosome (XY)

The internal sex organs of both male and female fetuses will look the same until about 7 to 8 weeks of pregnancy.

Around the eighth week of pregnancy, the gonads or sex glands begin to form into testes or ovaries for boys and girls respectively, and the outer genitals and internal reproductive organs start to gradually develop.

The key controlling factor in the development of sex organs is the hormones for male. When the male sex hormone, testosterone is present, it causes male organs to develop. Whereas, in the absence of hormones for males, the fetus develops female hormones and organs.

Several environmental and genetic factors can lead to abnormal genitalia. One possible cause for abnormal genitals in males, however, is the deficiency of hormones for male.

Likewise, the presence of male hormones in female fetus can cause it to develop atypical or abnormal genitalia. Apart from this, mutations in specific genes can also affect fetal sex development.

Summary:
Ambiguous genitalia is the abnormal formation of genitals or ambiguous external genitalia in newborns, making it difficult to determine the gender of the baby at birth.
Certain gene mutations, exposure to male hormones in females and deficiency of male hormones in genetic males are some of the known causes for this condition to occur.

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Chapter 2: What causes Ambiguous External Genitalia?

The development of external genitalia occurs as a result of interaction between three factors: hormone-dependent, hormone-independent and endocrine/environmental factors. These three factors interrelate in many complex ways to achieve the development of the male and female reproductive systems.

However, as mentioned in the previous chapter, congenital abnormalities or any imbalances or disruptions in the normal endocrine factors could result in ambiguous external genitalia. Let’s look at some causes in genetic males and genetic females in more detail below.

CAUSES OF AMBIGUOUS GENITALIA

Androgen Insensitivity Syndrome

Impaired testicular development

5a-Reductase deficiency

Testosterone biosynthesis defect

Mother’s ingestion of certain substances

Congenital Adrenal Hyperplasia (CAH)

Placental aromatase deficiency

Tumours

Maternal hormonal imbalance

Hormonal medications

Causes in Indian genetic females:

1. Congenital Adrenal Hyperplasia (CAH)

This is the most common cause of female genital abnormalities. Congenital Adrenal Hyperplasia or CAH is a genetic disorder wherein the adrenal gland produces the androgen male hormones in excess. This results in the birth of females with male organs as well. In this case, you will be asked to consult with an endocrinologist to help treat the condition.

Shortness of Breath

Heart attacks happen due to insufficiently oxygenated blood going from the heart and to the other organs in the body. Shortness of breath is a result of low oxygen levels in the blood. Since the amount of oxygen in the body is drastically reduced, the heart has to work harder to carry out its functions.

2. Placental aromatase deficiency

This is a rare disorder that impairs the conversion of androgen to estrogen leading to the birth for females with male organs.

Estrogen is the female sex hormone that is involved not just in reproductive development but also in bone growth and a number of other physiological processes as well.

Female infants born with this condition may, therefore, show genital abnormalities. They are also subsequently likely to be affected by primary amenorrhea, progressive virilisation and the absence of breast development.

3. Tumours

Tumors in the mother or the fetus can produce excess of the androgen male hormone, that affect the genital development of the newborn child and result in mixed genitalia or ambiguous gender at birth.

4. Maternal hormonal imbalance

Pregnant women with increased levels of testosterone or a hormonal imbalance are at an increased risk of passing this on to their fetus, which, in turn, can adversely lead to ambiguous external genitalia in Indian children.

5. Hormonal medications

The fetus can also be masculinized if the mother takes certain medications or substances hormones of males such as androgenic steroids or progesterone (sometimes given in early pregnancy to stop bleeding).

Causes in Genetic Males:

1. Androgen Insensitivity Syndrome

Androgen Insensitivity Syndrome (AIS) is a condition in which the fetus is unable to properly respond to the androgen male hormones. The insensitivity can be partial, mild or complete.

Because of its inability to respond to the male hormones, the fetus may exhibit female and male hormones, or external female sex characteristics or a combination of both male and female sex characteristics.

2. Impaired testicular development

This can be a result of genetic disorder causes or in some cases may occur even due to unknown causes.

3. 5a-Reductase deficiency

The 5-alpha reductase enzyme is an enzyme found in the male gonads. Deficiency of this enzyme impairs the ability of testosterone to convert to Dihydrotestosterone (DHT), the hormone that is responsible for the development of male sex characteristics.

4. Testosterone biosynthesis defect

At least four different enzymes are involved in the biosynthesis of testosterone. When there is a deficiency or lack of one or more of these enzymes or if the enzyme levels are deficient, it can inhibit the healthy development of the male reproductive system.

5. Mother’s ingestion of certain substances

The ingestion of certain substances with female hormones can also increase a genetic male’s risk of developing ambiguous external genitalia in males.

Antimicrobial cosmetics, certain kinds of toothpaste and soaps, plastic products with high concentrations of BPA and paraben and hormone-injected meat and dairy products are some examples of hormone-disrupting products or substances.

Summary:
Ambiguous genitalia generally occurs when there is a disruption in the hormonal process that influences tissue to become male or female. However, this is not the only causative factor.
Genetic disorder symptoms, tumours, family history of congenital adrenal hyperplasia (CAH) and prenatal exposure to or ingestion of certain medications and substances can also cause genital defects.

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Chapter 3: Recognising the symptoms of Ambiguous Genitalia

Symptoms of ambiguous external genitalia vary depending on the cause and/or when the problem occurred during pregnancy.

Ordinarily, identifying the signs and symptoms in babies born with this condition is only possible after the infant is born. However, in some cases, genital abnormalities may be suspected even before birth.

The following are some of the symptoms that may be recognised in genetic males and genetic females:

Symptoms in genetic females:

An unusually enlarged clitoris that closely resembles a small penis
Labia that may be fused and looks more like a scrotum
A lump of tissue within the fused labia that can feel or look like a scrotum with testes
A urethral opening that is located along the surface of the clitoris, above or below it
Electrolyte or hormonal imbalances

A consultation with a gynecologist might have to be undertaken in the case of observable ambiguous genitals in females.

Symptoms in genetic males:

Hypospadias or a condition in which the opening of the urethra may be located above or on the underside of the penis instead of the tip
A micropenis or an unusually small penis that is less than 2 to 3 centimetres and looks like an enlarged clitoris
Undescended testicles or cryptorchidism, which happens when the testicles have not moved into proper position within the scrotum before birth
A small scrotum that may have some degree of separation and resembles labia.

For ambiguous genitaled newborns, the doctor or physician will conduct a detailed physical examination to check for any of these symptoms. An andrologist might have to be consulted with in this case.

Health providers may also inquire about the medical history of the family as well as the parents’ in order to identify any genetic disorder causes and abnormalities and arrive at an accurate diagnosis of the underlying cause.

Symptoms of ambiguous external genitalia in females may include a closed or fused labia, an enlarged clitoris, urethral anomalies or tissue masses that feel like testes.
In genetic males, symptoms may include undescended testicles, a micropenis, hypospadias or a scrotum that resembles labia.

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Chapter 4: How is Ambiguous External Genitalia diagnosed?

”

Important:

“An ambiguous genital diagnosis can be distressing for parents. However, it is important that parents provide a safe and nurturing environment for the baby and keep themselves educated about their child’s condition. The child’s doctor can recommend the best treatment options for the baby after careful evaluation.”
– Dr Uma M, Consultant Family Physician and Diabetologist

If symptoms that raise suspicion of abnormal genitalia such as micropenis, labial fusion, undescended testis or hypospadias are apparent, a doctor may carry out a diagnosis on the basis of a physical examination, medical history of the parents, and/or other laboratory tests.

Lab tests and diagnostic procedures can include hormonal studies, a screening test for Congenital adrenal hyperplasia or CAH and a biopsy of the reproductive organs. After the diagnosis has been done, and the test results have been evaluated, doctors’ will present their recommendations and the various treatment options.

A detailed description of the diagnostic process has been given below.

Diagnosing ambiguous external genitalia:

Typically, the evaluation of a newborn with genital abnormalities may entail the following:

1. A detailed assessment of family medical history

Doctors may use the medical history of the parents to identify abnormalities or any patterns of disease in the family. Parents may be asked to give the following information:

History of consanguinity or consanguineous marriages in the family- this information is essential as it has been found to play a role in various genetic disorders and disorders relating to androgen synthesis such as Congenital adrenal hyperplasia (CAH)
History of any unexplained sibling or neonatal deaths in the family. This information helps to point towards the risk of CAH in the newborn infant
History of any fertility issues in the parents of the infant, grandparents, uncles or aunts
History of any adoption in the family
Pregnancy history including information regarding medications and drugs taken by the mother during pregnancy, especially oral contraceptive pills, steroidogenic drugs or any other androgens and endocrine disruptors as well as information regarding maternal diseases such as excessive cystic acne, hirsutism, androgen-producing tumours etc.
Results of the screening test done for Down’s Syndrome during pregnancy.

Learning about the family’s medical history will help the doctor choose screening tests that are right for the patient.

2. Physical examination

Physical examination of this condition in newborns may be carried out in three parts. The doctor may first conduct a general physical examination (GPE), followed by a specific physical examination.

If the appearance of the child indicates any existing health conditions after these preliminary examinations, a systematic exam comprising of several diagnostic and laboratory tests may be done.

Steps of the General Physical Examination (GPE):

During the general physical examination, the physician may evaluate the patient or child for vital signs and symptoms such as the following:

The weight of the child (which could be increased in case of Congenital adrenal hyperplasia)
The height of the child (abnormally short or stunted in case of Turner’s syndrome and signs of rapid growth in case of Klinefelter’s syndrome)
The child’s general health condition or status (in case of CAH, there may be medical complications that require immediate treatment)
State of Hydration (CAH is sometimes associated with varying degrees of salt loss)
Hypertension (in case of impaired androgen biosynthesis)
Dysmorphic or abnormal features
Skeletal deformities

Steps of the specific physical examination:

The specific physical examination is generally conducted by the doctor only after receiving proper consent from the parents. This physical examination will entail the following:

A detailed examination of the genitalia which may include evaluating the size and shape of the phallus and clitoris, the location, size and symmetry of the gonads, the anatomy of the urinary meatus or opening of the urethra, the structure of the vaginal orifice and genital swelling or labioscrotal folds
For adults, the hair growth pattern, pigmentation pattern, and breast development may also be evaluated.

Diagnostic tests:

Infants born with abnormal genitalia in India may be subject to one or more of the following diagnostic tests:

Blood tests such as the hCG test to check for hormonal imbalances
Neonatal imaging, ultrasonography or ultrasound, to determine the structure and presence of a uterus, gonads and other internal sex organs
Magnetic Resonance Imaging (MRI) for assessment in cases that are more challenging or inconclusive
Genital urethrogram to delineate the anatomy and position of internal reproductive organs. This test will involve X-rays as well as catheterisation of the openings between the genitals and the anus and, in some cases, even the use of dye. The test is particularly useful to plan for surgery.
Chromosome analysis to help check for genetic abnormalities
Skin and gonadal biopsies which are useful when diagnostic categories such as true hermaphroditism and dysgenesis are being considered. This will involve the removal of a small tissue sample from a specific area for the doctor to examine under a microscope.

If hormone levels are found to be very high or very low in the blood, the doctor may be able to immediately recognise the cause for the disorder. Once the cause has been identified, the hormone levels can very often be corrected.

Apart from the above mentioned diagnostic tests, the doctor or physician may also conduct specific tests that can help determine the gender of the baby. In India, this may include tests to ascertain the following:

The fertility potential of a female pseudohermaphrodite
The size of the penis and its potential to grow in a male pseudohermaphrodite
How the fetal brain is affected by male and female sex hormones
The ability of the internal reproductive organs to produce sex hormones for the appropriate gender

In some cases, doctors in India may also carry out additional screening and tests in order to determine if the baby is at an increased risk for health conditions such as cancer in the future.

All clinical procedures and diagnostic tests will be conducted by the physician or doctor only with the informed consent of the parents or the patient if he/she is competent to decide.

Summary:
The ambiguous genital diagnosis entails three steps: assessment of family medical history, detailed physical examination of the infant and diagnostic tests.
Diagnostic tests may include blood tests, ultrasound, MRI, chromosome analysis, genital urethrogram and sometimes even a biopsy.

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Chapter 5: Treating Genital Abnormalities

Once the physical examination and diagnostic tests for have been performed, the doctor or physician may suggest a gender for the baby on the basis of the information gathered from the tests.

The suggestion will be made after taking into consideration a number of factors, including:

Genetic disorder causes
The genetic sex of the baby
The future sexual and reproductive potential of the infant
Probable gender identity as an adult
The anatomy of the child

A discussion will be held with the parents, and a decision will be arrived at with the consent of the concerned family.

In some cases, however, it may be extremely difficult or impossible to assign a gender to an infant. Doctors may also be unable to predict the long-term implications of the disorder.

Having an interdisciplinary support group consisting of psychologists, endocrinologists, gynaecologists, surgeons, geneticists, urologists, and social workers may be helpful for ambiguous genitalia treatment.

The support medical team will be able to provide long-term guidance and support as well as multidisciplinary care to both the patient and the parents.

Treatment for ambiguous genitalia

Depending on the cause and symptoms, treatment might include corrective surgery or hormone replacement therapy. Parents are encouraged to think about the benefits of each treatment option as well as the possible risks and side effects before arriving at a decision.

In this day and age, most heart attacks can be treated successfully. It is important to note that a patient’s survival depends on how quickly they are treated. Quick thinking is even more crucial if the patient has a history of heart disease.

Having a multidisciplinary team as mentioned earlier can help parents feel more confident about the treatment approach that they choose.

1. Corrective surgery

Doctors may recommend surgery for babies with abnormal genitalia under two circumstances: to preserve normal sexual function or to create genitals that appear normal.

For example, for ambiguous external genitalia in girls, surgery to normalize sexual function may be required if a girl’s vagina is hidden under her skin. Whereas for boys, surgical treatment may be recommended to reconstruct an incomplete penis and make erections possible. In either case, it is unlikely that the doctor will recommend surgery during the neonatal period.

In case of an imminent threat to a newborn child’s health such as the absence of a urinary opening or the presence of malignant tissue, however, doctors may naturally schedule an immediate surgery.

Genital cosmetic surgeries, on the other hand, are typically offered when the parents of the infant are incredibly distressed.

Misconceptions of cosmetic genital surgeries

A lot of parents who give birth to children with this condition believe that fixing the condition earlier is the most practical solution as a child without an assigned gender may struggle to fit into society.

This is, however, a flawed notion.

Cosmetic genital surgery does not guarantee that a child will grow up to be physically, emotionally or sexually healthy.

Majority of doctors are, therefore, opposed to performing cosmetic genital surgery.

Surgically configuring the genitals of an infant may sometimes interfere with the biological functions of the child. The child may grow up to have sexual dysfunction or may experience diminished sexual sensation and in some cases, even chronic pain.

Parents are, therefore, increasingly advised to delay such cosmetic surgeries and wait until the patient is old enough to make the decision themselves. Moreover, the results of the procedure may not always be satisfactory, and in some cases, repeat surgery may have to be performed.

2. Hormone replacement therapy

Hormonal treatment like surgery may be delayed until the infant or patient is of an appropriate age. In case the doctors think there is an imminent threat to the child’s health. However, hormonal therapy may be started immediately.

Newborns with classic Congenital Adrenal Hyperplasia (CAH), for example, need to start endocrinologic therapy soon after birth. If left untreated, it can cause a number of symptoms including heart rhythm problems, very low blood sodium levels, low blood glucose, low blood pressure, vomiting, shock and/or coma and in some cases even death.

Elective sex hormone treatments, conversely, are administered to the child only after they have reached the age of puberty.

The administration of exogenous sex hormones carries a number of risks and may even result in behavioural the and physiologic changes in the child. As a result, doctors prefer to wait and allow patients to decide what risks they would like to assume.

3. Ongoing support and care

Besides the obvious physical symptoms, this condition can also have considerable social and emotional implications on the patient or the child.

Ongoing support and care is, therefore, crucial and needs to be included as a part of the treatment plan.

Patients need to be given the benefit of full disclosure of their medical condition. Working with a psychologist will also help the child navigate and cope with the challenges of the situation. Apart from this, the child also needs to be regularly monitored and screened for any complications such as cancer.

Summary:
Treatment options for ambiguous external genitalia include corrective surgery and/or hormone replacement therapy.
Normally, in the case of genital cosmetic surgeries and elective hormone treatments, doctors would recommend waiting until the patient or child reaches the age of puberty before starting treatment.

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Conclusion

Ambiguous genitalia can be a challenging condition for both parents and children to deal with. Parents should, however, try to invite open discussions with their child and answer their questions as honestly and clearly as possible. Treat the child’s questions and concerns with respect and let them know that your love for them is unconditional!

When parents can come to terms with their own feelings, it gives the child reassurance and helps counteract feelings of fear, confusion, anxiety and sadness in the child. So always try to celebrate your child for who they are!

References

Q1. Is abnormal genitalia always obvious at birth?

Yes, usually ambiguous or abnormal genitalia is always evident at birth. The external sex organs of the affected child will appear to have characteristics that are neither wholly male nor wholly female or may have both female and male hormones.

Q2. What are the risk factors for ambiguous genitalia?

Possible risk factors for ambiguous genitalia include a history of infertility, genital abnormalities, unexplained deaths of children during early infancy in the family, abnormal physical development during puberty and an inherited disorder called congenital adrenal hyperplasia (CAH).

Q3. Is surgery always necessary for children born with genital abnormalities?

No, surgery is not always necessary to correct genital abnormalities. Some babies could have conditions that pose a risk to their health and, therefore, require immediate surgery. In other cases, surgery may be done solely for cosmetic reasons and is not always viewed as essential.

Q4. How are babies born with ambiguous external genitalia assigned a sex?

Doctors generally perform a number of preliminary examinations and diagnostic tests on babies born with atypical genitalia. Based on the results of these tests and after taking into consideration a number of other factors such as the anatomy of the child, the baby’s genetic sex, the future sexual and reproductive potential of the infant and probable gender identity, doctors may assign a sex after consulting the child’s parents.

Q5. Is the sex assignment for persons with atypical genitalia always accurate?

In most cases, persons with ambiguous external genitalia are happy with the sex that is assigned to them. However, in some cases, patients may be dissatisfied or discontent with the sex that has been assigned to them and may have a strong desire to change their bodies.

Q6. Can a person with abnormal genitali have children as an adult?

Girls with normal internal sexual organs may be able to lead a fertile reproductive life. So is the case with women who have congenital adrenal hyperplasia (CAH), although they may have to undergo hormonal treatment in order to get pregnant. Others may, however, experience some difficulty in conceiving a child.

Q7. What are some complications associated with ambiguous genitalia?

Two major complications associated with ambiguous genitalia are infertility and an increased risk of certain cancers. Not all persons with this condition are, however, infertile.

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