Host:

If a baby is born with XX karyotype, but there's no uterus and ovaries, rather there are testes and vas deferens. Is the baby a male or a female? Some babies are born with uncertainty in sex assignment. These babies may have differences in sexual development.

Today we've invited Dr Sarah Poon, Associate Consultant of the Department of Paediatrics and Adolescent Medicine of the Hong Kong Children's Hospital to explain this to us.

Can you share with us what is differences in sexual development?

Dr Sarah Poon:

Generally speaking, these patients may have anomalies in their sex chromosomes, or problems in development of their gonads, that is testes or ovaries, or development of their internal or external genitalia is different from other individuals. These conditions are termed as differences in sexual development.

Host:

What symptoms will the patient have?

Dr Sarah Poon:

Some patients may, as a newborn, present with ambiguous external genitalia that doctors find hard to decide if the baby is a boy or a girl. For example, the baby may have severe hypospadias or a very short penis. As for baby girls, the clitoris may appear enlarged, and resembles the appearance of a penis.

Host:

What are the causes of abnormal sexual development?

Dr Sarah Poon:

The process of sexual development is very complicated. It involves sex chromosome determination, development of gonads and internal and external genitalia. These involve both internal and external factors which may cause abnormal sexual development. Some internal factors such as genetic mutations cause problems in gonadal development. Some people have insufficient sex hormones, or have mutations in the sex hormone receptor gene. These may all result in these conditions.

As for external environmental factors, for example, if a mom takes medications containing androgens during her pregnancy, this may cause differences in sexual development in the fetus as well.

Host:

Is sex, whether it is male or female, determined in the early stages of the embryo? When do reproductive organs take shape?

Dr Sarah Poon:

In fact, generally speaking, karyotype is determined at fertilization. Our eggs have an X chromosome. As for sperms, they have either an X or Y chromosome. Hence, after fertilization, if it is an XY fertilized egg, it will evolve or develop into a male baby. Because the Y chromosome results in production of male hormones from the testes which results in the development of the fetus into a male.

On the contrary, if it is an XX fertilized egg, it will develop into a baby girl. The development of the entire internal and external genitalia should have been completed before the baby is born.

Host:

But I know some reproductive organs or sexual characteristics will not be formed until later. For example, the Adam's apple, or breasts only appear during puberty. In fact, will the patient only present with the disorder later?

Dr Sarah Poon:

This is partly correct. Differences in sexual development is a disorder that one is born with. But some people are only diagnosed during puberty. As you said, a normal teenage girl has breast development during puberty. She will also have growth spurt and finally start of menstruation. However, for some patients with differences in sexual development, they may appear like a girl but do not have menstruation until 15 or 16 years old. Some may even develop signs of virilization, such as deepening of voice. This is the time when doctors may need to raise suspicion on the possibility of differences in sexual development.

Host:

Some patients may have vague symptoms. How do you diagnose and confirm? Can it be diagnosed during pregnancy?

Dr Sarah Poon:

In terms of diagnosis, generally speaking, the doctor will examine the external genitalia. For example, we measure the penile length, determine the position of the urethral and anal openings, as well as location and size of the gonads. After completing these checks, if the patient is at pubertal age, we will of course also examine for breast development and hair distribution.

As for investigations, we usually start with blood tests to see if sex hormones are adequate. Besides, we will do ultrasound and MRI to look at the urinary system, as well as the internal genitalia. Finally, we now know that there is a panel of disease-causing genes that can lead to differences in sexual development. Hence, we will also work with our geneticists to perform analysis of the karyotype as well as genetic tests for disease-causing genes.

Host:

For this particular group of patients, what treatments are available? And what factors will be considered when determining the final gender of the patient?

Dr Sarah Poon:

In terms of management, every case, actually depends on the sex of rearing of each individual patient. Some patients may need hormonal medications, while some patients may need surgery on their genitalia. For some, as they have abnormal development of the gonads, the risk of developing tumour in the future is heightened. We will the need to discuss with the patients and their families on whether we should have the gonads removed surgically.

Referring to what you said before, regarding how gender is determined, this decision cannot be rushed as well. Generally speaking, we need to consider many factors. In addition to the appearance of the external genitalia, we also need to take into account karyotype of the patients, their gender identity, cultural background and potential for future fertility. Each of these factors is important. When considering these factors, when younger children are involved and they are unable to understand complex medical information, we will work with clinical psychologists together to explain their diagnosis in a gradual manner, subtly explaining these diagnoses. We hope that children can participate in the decision-making process. We will take into account and respect their wishes and considerations fully.

Host:

Do your have some cases that you can share with us?

Dr Sarah Poon:

There was a baby born with female external genitalia like any female baby. But when the baby was nine months old, she was found to have hernia. She was brought to us for further workup. We found out that in fact this baby had an XY male karyotype. Subsequent ultrasound and MRI revealed testes inside her body. Blood tests and genetic tests that followed confirmed that this child had a condition called 5α-reductase 2 deficiency such that the body could not produce certain androgens, resulting in genitalia that is different from other males. The family was very puzzled by the diagnosis.

We recommended taking six months to observe the child's behavior. At the same time, we tried some hormonal medications and see how the external genitalia responded. After six months, the genitalia responded very well to the topical hormonal medication. At the same time, the family observed masculine behaviors in this child. For example, he liked to fight like a superman, play Lego and play with toy cars. Hence, after discussion with the medical team, we decided to change the sex of rearing to male.

Host:

Thank you doctor for sharing with us today. That's almost time today. Goodbye.