When your sex doesn't align with your chromosomes

The recent controversy about Algerian boxer Imane Khelif’s (right) sex begun after Italian boxer Angela Carini’s (left) outburst following her defeat by the former (pictured here) in their Olympics women’s 66kg preliminary boxing match in Paris. Imane is said to have DSD. — AP

Differences or Disorders of Sex Development (DSD) refer to conditions where a person’s sex development doesn’t follow the usual patterns.

This medical term covers various conditions that involve a person’s chromosomes, hormones, reproductive organs and genitals.

Sometimes, you might hear the term “intersex” used instead.

It’s important to avoid outdated terms like “hermaphrodites”, which are medically misleading and offensive to people with DSD.

DSD can become noticeable at birth, puberty, or even later on in life.

Most often, it’s identified when a baby is born with ambiguous genitalia, meaning that the genitals don’t clearly appear male or female.

For instance, a baby might have genitals that are not clearly identifiable as male or female, or a child might go through unexpected body changes during puberty.

These situations can be stressful for both the child and their family.

Normal and abnormal development

Sex development starts while the baby is still in the womb, based on their sex chromosomes inherited from their parents.

Mothers contribute an X chromosome, while fathers provide either an X or a Y chromosome.

This results in either XX (female) or XY (male) combinations.

Around the sixth week of pregnancy, if the baby is male, a gene on the Y chromosome triggers the formation of testes, which produce testosterone.

This hormone is essential for developing male external genitals.

If the baby is female, i.e. lacking a Y chromosome, the fetal tissue forms ovaries, a uterus and fallopian tubes.

Hormones and genes also play crucial roles in this development.

DSDs can arise from various factors, including genetic mutations.

For example, some children might have extra or missing sex chromosomes, resulting in patterns like XXY (Klinefelter syndrome), XO or XY/XO mosaicism.

In other cases, a person might have typical sex chromosomes (XX or XY), but their reproductive organs and genitals develop differently.

This can be due to:

• Genetic factors: Changes in genes, either inherited or spontaneous.
• Exposure to substances: Effects of certain medications or hormones during pregnancy.
• Developmental issues: Problems in the womb affecting hormone production or organ formation.

Importantly, DSDs are not caused by anything the parents or child did or didn’t do.

Photos of Imane (circled) with family members as a child. — YOUCEF ZAGHBA/Facebook

Types of DSDs

DSDs can vary in severity and presentation:

> Hypospadias

In mild cases, a boy’s urinary opening is on the underside of the penis instead of the tip.

Severe forms where the opening is at the perineum or where the testes is not descended in the scrotum require further evaluation.

> Female chromosomes with ambiguous genitals

Some individuals with XX chromosomes might have ambiguous or atypical genitalia due to conditions like congenital adrenal hyperplasia (CAH), which affects hormone levels and requires prompt treatment.

> Male chromosomes with ambiguous genitals

Individuals with XY chromosomes might have genitals that appear more female due to conditions like 5-alpha reductase deficiency, androgen insensitivity syndromes or gonadal dysgenesis.

> Mixed sex characteristics

Some people can have both ovarian and testicular tissue, resulting in ambiguous genitalia.

This is known as ovotesticular DSD.

Their chromosomes can be XX, XY or mixed.

> Unusual chromosome patterns

Patterns like XY/XO mosaicism, XX/XO mosaicism or XXY (Klinefelter syndrome) can also occur, leading to varied physical characteristics.

Personalised management crucial

Managing a child with a DSD involves a personalised and compassionate approach, often including medication, hormone therapy, surgery, or even no treatment at all.

If surgery is not medically necessary, it can often be postponed until the child is old enough to participate in the decision-making process.

Initial assessments typically include genetic tests, hormone evaluations and imaging.

For parents, it can be challenging when a baby’s sex isn’t immediately clear.

Adolescents diagnosed later might experience stress and confusion, especially if they face teasing or lack of understanding from others.

Providing accurate medical information and psychological support for both the child and family can be very beneficial.

As children grow, it’s essential to discuss their condition openly and supportively, to help them understand their bodies without shame.

Gender identity is complex and influenced by genetics, hormones and other factors not yet fully understood.

For instance, girls with complete androgen insensitivity syndrome (CAIS) might have the male Y chromosome, but develop female bodies and typically identify as girls.

Conversely, girls with CAH might have higher testosterone levels, influencing their behaviour, but still often identifying as girls.

In cases of significant DSD, determining gender at birth can be challenging.

In some cases, as they grow older, adolescents with DSD might identify with a different gender to that assigned at birth, and treatment options should be rediscussed with the family.

Managing severe DSDs can be complex.

It involves more than just medical or surgical care; but also emotional support for the child and family.

With accurate diagnosis, appropriate treatment and acceptance, many children with DSD grow up to lead healthy, fulfilling lives.

Dr Jeanne Wong Sze Lyn is a consultant paediatrician and paediatric endocrinologist. For more information, email [e-mail]. The information provided is for educational purposes only and should not be considered as medical advice. The Star does not give any warranty on accuracy, completeness, functionality, usefulness or other assurances as to the content appearing in this column. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.