47, XYY syndrome

The signs and symptoms of 47, XYY syndrome can range from barely noticeable to more severe. It is thought that some males with 47, XYY syndrome may never be diagnosed because the signs and symptoms may not be noticeable.^[2] For other males, signs and symptoms such as low muscle tone (hypotonia) and/or speech delay may begin in late infancy or early childhood. Some boys with 47, XYY syndrome may have difficulty in certain subjects in school such as reading and writing. However, boys with this syndrome do not typically have intellectual disability.^[1][3]

Other signs and symptoms of 47, XYY syndrome may include asthma, dental problems, and acne.^[2][3][4] Boys with the syndrome don’t typically have physical features different from most people, but they may be taller than expected. These boys are not expected to have differences in the appearance of the sex organs (genitalia). Some males with 47, XYY syndrome have behavioral differences such as autism spectrum disorder (usually on the milder end) or attention deficit hyperactivity disorder (ADHD). Boys with 47, XYY syndrome are also at an increased risk to have anxiety or mood disorders.^[2]

Most boys with 47, XYY syndrome go through normal sexual development, and fertility is expected to be normal. However, some boys with the syndrome may develop testicular failure (when the testes can’t produce sperm or testosterone), which can lead to problems with fertility.^[2][5][6] 

47, XYY syndrome is caused by having an extra copy of the Y chromosome in each cell of the body.^[1] The Y chromosome is one of the sex chromosomes, and the other sex chromosome is called the X chromosome. Most people have two sex chromosomes, with girls having two X chromosomes, and boys having one X and one Y chromosome.

Boys with 47, XYY syndrome have one X chromosome and two Y chromosomes in each cell of the body. This typically happens due to a random event when a sperm cell is formed that causes the sperm cell to have two Y chromosomes. When a sperm that has two Y chromosomes fertilizes an egg (which has an X chromosome), the resulting baby will be a male with two Y chromosomes and one X chromosome.^[1] It is also possible that a similar random event could occur very early in an embryo’s development. This can produce a boy who has some cells that have two sex chromosomes and some cells that have an extra Y chromosome.^[1]

It is not fully understood why an extra copy of the Y chromosome causes the features associated with 47, XYY syndrome. It is thought that the tall stature seen in some males with the syndrome is caused by having an extra copy of a gene that is located on the sex chromosomes called the SHOX gene. This gene provides instructions to the body to control growth of the bones. People who have an extra copy of the Y chromosome also have an extra copy of the SHOX gene, which could explain why they may be taller than expected. Another gene that is thought to cause the signs and symptoms of 47, XYY syndrome is called NLGN4Y. This gene is located on the Y chromosome and provides instructions to the body that helps form connections between the cells in the brain. It is thought that having an extra copy of this gene may cause the learning problems associated with 47, XYY syndrome.^[2]

47, XYY syndrome is usually not inherited from a parent. Instead, it is typically caused by a random event that happens during the formation of a sperm cell before conception (when the sperm fertilizes the egg). Even though this random event occurs in the sperm cell of the father of a person with 47, XYY syndrome, the syndrome is not inherited from the father because the father himself typically does not have the syndrome.^[1]

It is uncommon for more than one person in a family to have 47, XYY syndrome. If a couple has a child with 47, XYY syndrome, the chances for the couple or family members to have another child with the syndrome are not increased. Men who have 47, XYY syndrome themselves are also not thought to be at an increased risk to have a child with chromosome differences. Some sperm cells of a man with 47, XYY syndrome will have an extra Y chromosome. However, it is thought that these cells are less likely to be able to survive to fertilize an egg. Therefore, the chances for a man with 47, XYY syndrome to have a child with a sex chromosome abnormality are not thought to be increased.^[2]

People with questions about the chance to have a child with a chromosome abnormality are encouraged to speak with a genetic counselor or other genetics professional. 

47, XYY syndrome may be suspected when a doctor observes signs and symptoms that can be associated with the syndrome such as low muscle tone (hypotonia), speech delay, or learning problems in school. A doctor may then order testing to see if there is a genetic explanation for the signs and symptoms. Tests that may be ordered include:^[2]

• Karyotype: a test that is used to view all the chromosomes in a cell
• Chromosomal microarray: a test that looks for extra or missing chromosomes or pieces of chromosomes

In some cases, 47, XYY syndrome may be suspected prenatally based on routine screening tests. A diagnosis can be confirmed with prenatal tests such as an amniocentesis or chorionic villus sampling (CVS).^[2]

It is thought that some people who have 47, XYY syndrome are never diagnosed because they do not have severe signs or symptoms of the syndrome.^[2] 

The signs and symptoms of 47, XYY syndrome can be managed with a variety of therapies. Occupational therapy may be recommended for infants and young boys who have low muscle tone (hypotonia), and speech therapy may be recommended for boys who have speech delay. Boys with 47, XYY syndrome may be in special education at school, or they may have extra help in some classes.^[2][5]

Other management options for boys with 47, XYY syndrome may include behavioral therapy or medications for boys with attention deficit hyperactivity disorder (ADHD) or behavioral problems. If autism spectrum disorder is present, applied behavioral analysis (ABA) therapy may be recommended.^[2] In some cases, hormonal therapy may be used.^[7]

The long-term outlook for people with 47, XYY is typically good. Boys with this syndrome can do well both in school and in building social relationships. Men with 47, XYY syndrome can also have successful careers and families of their own.^[2] Therapies and other management for the syndrome can be important in allowing affected males to reach their full potentials.^[5]