By Stacey Richards

XX male syndrome, also known as XX testicular disorder, is a rare disease where affected individuals with two X chromosomes in each cellhave a male appearance.

XX male syndrome is a condition in which the sex chromosomes of an individual do not agree with the physical sex of the affected person. Normally there are 46 chromosomes, or 23 pairs of chromosomes, in each cell. The first 22 pairs are the same in men and women. The last pair, the sex chromosomes, is two X chromosomes in females (XX) and an X and a Y chromosome in males (XY).In XX male syndrome, the person has female chromosomes but male physical features

Normally, a combination of an X chromosome each from a male and female will result in female child, and a combination of the Y chromosome from a male and X chromosome from a female will result in male child. Either X and Y chromosomes are carried by individual sperm cells which means that the gender of a child depends on males.

This condition has an incidence of 1 in 20,000 people, and is rarely an inherited problem. In 80 percent of cases, the reason why XX male syndrome occurs is due to the abnormal exchange of genetic material (translocation) of the Y chromosome segment, which contains the SRY gene, during the production of sperm in the testicles. The result is that the SRY gene is misplaced, almost always on the X chromosome, and this means that X chromosome containing sperm will have the SRY gene present in them.

When this affected sperm then fertilizes an X chromosome egg (ovum) in the female, the result is two X chromosomes in a fetus where the SRY gene is present, thus resulting in male physical characteristics.An important note here is that there are usually no issues with the patient’s gender role and identity. Most people with the condition consider themselves to be male.

In the other 20 percent of cases, patients with XX male syndrome don’t carry the SRY gene. The reason why male characteristics develop in an XX chromosome individual in these cases is unknown, although other genetic defects are thought to be responsible. These patients are also more likely to have ambiguous genitalia compared to those who do have the SRY genepresent.Unfortunately, this form of XX male syndrome may make gender identity an issue for the affected individual.

The clinical picture

The clinical presentation of patients with XX male syndrome will depend on whether the mentioned SRY gene is present or not.In patients with the SRY gene, the signs and symptoms of the condition may include the following:

– Presentation after puberty with short stature.
– Normal pubic hair and penis, but with small testes. In some cases, there may be an empty scrotum due to cryptorchidism (hidden testes), and hypospadias (where the urethral opening of the penis is not located in its normal position).

– Gynecomastia (breast development).
– No sperm production resulting in infertility.

The clinical features of SRY–negative individuals may include a higher chance of cryptorchidism, and penoscrotal hypospadias where the urethral opening is closer to the pelvis. Long-term complications may also include erectile dysfunction, a lowered libido, reduced male secondary sexual characteristics (physically seeming more female than male), depression, and osteopenia due to decreased production of testosterone.

Diagnostic methods

The diagnosis of XX male syndrome needs to be suspected in male children going through puberty who are experiencing the mentioned signs and symptoms. There are cases where babies may be suspected of the condition, due to the possibility of hypospadias and cryptorchidism, but as mentioned the penis and teste sizes are usually normal at this stage. There are other genetic conditions that can present in similar ways, so genetic testing will be important in confirming where the issue lies. This is done by using techniques such as polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) to detect the SRY gene on an X chromosome.

The diagnosis of the condition during pregnancy, with pre-natal testing, is also possible in those individuals who have an increased risk of developing SRY-positive XX male syndrome.

Management

The golden standard of managing XX male syndrome is by testosterone replacement in order to stimulate male secondary sexual characteristics such as increased muscle mass in the chest, shoulders broader than the hips, and increased penis and testicular size.

The testosterone replacement can also help prevent the growth of breast tissue, but if they have developed, then surgical reduction may be considered.

The most important aspect in the management of the condition is the psychological well- being of the affected individual. Adolescence is already hard enough with teenagers having to deal with schoolwork, bullies and peer pressure, and this is for those who are already comfortable knowing what gender they are. There are those though who do find it difficult to psychologically identify what gender they are, and we don’t want to exclude these individuals or say that their concerns are not as important to be aware of as those with physically ambiguous features.

It becomes difficult for teenagers with XX male syndrome to try and fit in and not be ridiculed for their physical appearances, so psychological counselling and support is paramount in these individuals.

Patient experiences

Something that was discovered while compiling this article was that there are very little online forum and support groups available which raise awareness of XX male syndrome. A consistent statement made by those affected by the condition is that they struggle to find others with the same problem for support and advice.

Mark, a 30 year old man, affected with XX male syndrome, recalls his story where during high school he was never really interested in girls, and that he wasn’t really aware of puberty or that his body had to undergo certain changes as he wasn’t taught about it by his parents or teachers. He assumed then that there wasn’t anything wrong, but eventually did have his testosterone levels checked when he was 25 years old due to feeling persistently fatigued, and it was discovered that they were extremely low. Genetic testing was also done which confirmed that he had XX male syndrome. Testosterone therapy was started, but he still complains of feeling tired and says that he feels like something is just missing.

Another affected individual shared her story where she was diagnosed with XX male syndrome in the 1980s. When she was 13, she had male characteristics but her development had stopped at that stage of her life. In essence, she looked like a teenage boy. She found it very difficult to make friends during her teenage and early adulthood years, but by the time she was 22 she had a girlfriend. This relationship failed though because she couldn’t function sexually as a male, and her girlfriend found her physical characteristics to be more on the feminine side. It was then that she decided to be assessed and investigated further by doctors. She was then diagnosed as having SRY-negative XX male syndrome, but being the 1980s, she was informed that she was between male and female, which caused a lot of confusion for her. She was never started on testosterone replacement, but rather estrogen replacement therapy. This form of treatment then facilitated her decision for sex reassignment surgery in order to identify as female, because she was led to believe by her doctors that this was the gender she should associate with.

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