XX male syndrome

**XX male syndrome**, also known as **de la Chapelle syndrome** and **46,XX testicular difference of sex development** (**46,XX DSD**), is a rare intersex genetic disorder. People with this disorder have two X chromosomes, meaning they are genetically female, but they have a male phenotype (appearance and body).

About 80% of XX males syndrome have the SRY gene, a gene found in the Y chromosome that causes male traits, that has crossed over into their X chromosomes. XX males with the SRY gene usually appear as a normal male and may not know they have XX male syndrome until later in life. A smaller amount of XX males do not have the SRY gene. They usually are not fully masculinized and may have ambiguous genitalia, meaning their genitalia may not be fully developed and may have female traits. All XX males are infertile because they cannot produce sperm.

About 1 in 20,000 to 30,000 people have XX male syndrome. It is also known as de la Chapelle syndrome, which is named after Finnish geneticist Albert de la Chapelle, who first found the disorder.

## Symptoms

Normally, people are born with one of two pairs of sex chromosomes. They may have two X chromosomes (XX) or one X chromosome with a Y chromosome (XY). Normally, people with XX chromosomes look female while people with XY chromosomes look male. However, people with XX male syndrome have XX chromosomes but are male. Many XX males look like a normal male, but some may not be fully masculine. XX males are usually shorter than XY males. Some XX males develop gynaecomastia during puberty. Gynaecomastia is a condition where a male has larger breasts. All XX males who have been reported have azoospermia, a condition causing males to not produce sperm. This means all XX males are infertile. XX males who do not have the SRY gene in their genes are more likely to have ambiguous genitalia. XX males usually have normal body and pubic hair, penis size, and libido (sexual desire).

## Genetics

The SRY gene is a gene found in the Y chromosome. This is an important gene that helps the body make male traits, like having a penis and body hair. However, about 80% of XX males have the SRY gene even though they do not have a Y chromosome. This is because the SRY gene moved to an X chromosome. The SRY gene can make someone appear male even if they have XX chromosomes. About 20% of XX males do not have the SRY gene. It is not known how an XX male without the SRY gene can appear male.

XX males who do not have the SRY gene are more likely to have ambiguous genitalia. Usually, people will have male genitalia (penis, testes, scrotum) or female genitalia (vulva, vagina, ovaries, uterus). However, people with ambiguous genitalia may have traits of both, which are usually underdeveloped, or underdeveloped parts of normal genitalia. Some of the traits an XX male without the SRY gene can have are a micropenis (unusually small penis), hypospadias (the urethra is not at the top of the penis), or undescended testes (the testes are in the lower abdomen and not outside the body).

## Diagnosis

XX male syndrome is diagnosed through a karyotype. This is a test done by geneticists of someone's DNA to make a map of their chromosomes. This would find that someone who is male actually has XX chromosomes. Sometimes, tests on hormones are done too.

Most XX males have a fully male appearance and body, so they are not diagnosed at birth and are usually unaware they have XX male syndrome. They are usually diagnosed at puberty, if gynaecomastia (large breasts in a male) develop, or during their adult life when they learn they are infertile and want to know why. XX males without the SRY gene may have ambiguous genitalia, which can be found at birth. Because most XX males appear as a normal male, it is estimated that many XX males are undiagnosed and do not know they have XX male syndrome.

Sometimes, if a baby has ambiguous genitalia, surgery will be done. This surgery won't be done to fix the genitalia, but to look at it instead. This will find the internal genitalia of someone, which includes testes or ovaries.

## Treatment

Some XX males may get counseling to help them with their gender identity. Others may get testosterone therapy to become more male-appearing. Some XX males may get estrogen therapy to become a female instead. XX males with ambiguous genitalia may get surgery done to make their genitalia look more male or female.

Because XX males are infertile, some choose to adopt or get sperm donations to have kids.

## Prevalence

It is estimated that 1 in 20,000 to 30,000 males has XX male syndrome.

## Infobox (medical condition)

- **name**: XX male syndrome
- **synonym**: De la Chapelle syndrome, 46,XX testicular difference of sex development
- **specialty**: Medical genetics
- **onset**: Prenatal
- **duration**: Lifelong
- **diagnosis**: Karyotype