XXXYY syndrome

**XXXYY syndrome** is a very rare genetic disorder. Males usually have one X chromosome and one Y chromosome, but people with XXXYY syndrome have three X chromosomes and two Y chromosomes. They have 49 chromosomes instead of 46. There have only been eight cases of it seen in medicine. Little is known about XXXYY syndrome. Symptoms include intellectual disability, genital issues, and physical deformities. It was first seen in 1963.

## Symptoms

Because XXXYY syndrome is very rare, there is not much known about it. The symptoms vary, but are usually similar to other disorders where someone has an extra X or Y chromosome.

### Physical

XXXYY syndrome causes someone's body to have deformities (unusual or misshapen parts of the body). People with the disorder may have hypertelorism (widely spaced eyes), a larger forehead, a wide nasal bridge, epicanthic folds (skin folds in the inner eye), and a small chin. People may also have clinodactyly (curved or bent fingers or toes) and radioulnar synostosis (fusion of the ulna and radius bones in the arm). These symptoms are common in disorders where someone has extra sex chromosomes. Someone with XXXYY syndrome may also have kidney or dental issues.

### Reproductive

Only one person with XXXYY syndrome had tests done on his hormone levels. He had low amounts of testosterone but high amounts of the lutenizing hormone and follicle stimulating hormone. Another common symptom is issues with the genitalia. This can include a micropenis (very small penis) or undescended testes (where the testes are in the lower abdomen instead of outside the body). Adults with the disorder do not have much facial hair and may have a high-pitched voice.

### Mental

Every person with XXXYY who has been seen has a developmental delay or intellectual disability. Adults with the condition have a moderate to severe intellectual disability. People with a moderate intellectual disability have a mental state similar to six- to eight-year-olds. They can live on their own and have jobs, but need support. People with a severe intellectual disability have a mental state similar to a three- to five-year-old. They largely depend on caregivers. Some examinations of the disorder say that people with it are "generally passive". Other reviews say that people with it struggle with controling their emotions. Behaviors associated with autism are also common.

## Cause

XXXYY syndrome is caused by nondisjunction. This is when the gametes (egg or sperm) produce too many chromosomes when forming a fetus. Usually, chromosomes that pair with another will separate and someone will have a normal amount of chromosomes. But in nondisjunction, this does not happen. Because people with XXXYY have three extra chromosomes, they go through multiple steps of nondisjunction. This is not caused by the parents.

## Diagnosis

Like other disorders that cause people to have extra or missing chromosomes, XXXYY syndrome is diagnosed through a karyotype. This is a test done by geneticists that finds how many chromosomes someone has and if there are any problems with them. This test will show that someone has three X chromosomes and two Y chromosomes instead of one of each. One case of XXXYY syndrome was diagnosed before birth through amniocentesis. This is a process that can find issues in unborn babies. This case did not survive to birth.

## Prevalence

XXXYY syndrome is very rare. There have only been eight reported cases. It is estimated that less than one in one million people have it. It is not known if there are less severe cases of XXXYY syndrome that have not been diagnosed.

## History

XXXYY syndrome was first found in 1963. A 23-year-old man with an intellectual disability was tested because he had traits of Klinefelter syndrome, where they found he had three X chromosomes and two Y chromosomes. It was one of the later disorders with extra sex chromosomes that was discovered. For example, XXYY syndrome, another disorder where a male has an extra X and Y chromosome, was found in 1960. It had three found cases by the time XXXYY syndrome was found. The next time the condition was found was eleven years later in 1974. By 1995, five cases were found. As of 2023, three cases have been found since 2000.

Because XXXYY syndrome is so rare, not much is known about it. Its prognosis (how a disorder's symptoms get worse or better over time) is not known.

## Infobox (medical condition)

- **name**: XXXYY syndrome
- **synonym**: 49,XXXYY syndrome
- **specialty**: Medical genetics
- **symptoms**: Intellectual disability, physical deformities, genital issues
- **onset**: Prenatal
- **duration**: Lifelong
- **diagnosis**: Karyotype
- **frequency**: Only eight reported cases