Answers to questions families often have about caring for their child with XXY (Klinefelter) syndrome

XXY or Klinefelter syndrome is a chromosomal condition that affects male physical and cognitive development. The condition is caused by an extra X-chromosome being present in each cell - with a karyotype (chromosome complement) of 47,XXY instead of the typical 46,XY male karyotype. The condition can affect physical, language, and social development; the signs and symptoms can vary significantly among affected individuals. The most common features associated with the diagnosis are testosterone deficiency and infertility.

In addition to the most typical XXY karyotype, other chromosome abnormalities can lead to a similar presentation. These include XY/XXY mosaicism, where a percentage of cells are normal (46,XY), and a percentage have an extra X chromosome (47,XXY). Individuals with mosaicism may still be fertile, depending on the percentage and distribution of normal XY cells. It is also possible to have more than one extra X chromosome, for instance 48,XXXY. The incidence of more than one additional X chromosome is less common and is typically associated with a more severe phenotype and intellectual disability.

Characteristics of individuals with XXY syndrome evolve with the developmental stage. The manifestations vary from person to person and may be subtle. Infants may be described as "easy" babies, may show developmental delays in some or all areas, particularly language, and may have hypotonia (low muscle tone). Toddlers with this syndrome may have continued language delays or be diagnosed with sensory integration disorder, auditory processing problems, or autism spectrum disorders. They may also begin measuring taller than their peers. Children with XXY syndrome may require academic, social, and emotional support. Adolescents may enter puberty at the normal time, but then have decreased facial and body hair, decreased muscle development, smaller testicles, and swelling of the breasts (gynecomastia). Depression and anxiety may occur at this age. Older teens and adults may not look different from other males their age, except possibly taller. They are generally infertile without invasive fertility treatment, although with normal sexual function. Osteoporosis (weak/brittle bones) is often found in older teens and adults with XXY syndrome.

Other common characteristics and symptoms may include:

• Rounded body type, overweight
• Hand tremors
• Decreased activity and endurance level
• Sleep abnormalities
• Difficulties in social situations (shy, immature, passive) with low self esteem
• Easily frustrated
• Autistic features

Chromosome testing (karyotyping) will confirm the diagnosis of XXY syndrome. As typically chromosomes from approximately 20 cells are counted in standard karyotyping, low-percentage mosaicism may be missed. Additionally, a karyotype of blood cells reflects the karyotype in only one tissue.

In the past, XXY syndrome was not usually diagnosed until puberty or adulthood. However, when younger children have chromosome testing as part of an evaluation of developmental delay and hypotonia, boys with this condition are being identified as toddlers and preschoolers.

Although the range of features is wide; most individuals with XXY will lead normal lives with a normal life expectancy. Boys diagnosed with this condition early in life that have received developmental therapies, educational interventions, social support, and testosterone therapy may have better outcomes.

No family history is expected. Klinefelter syndrome usually occurs sporadically or randomly.

In most cases, testosterone is measured in adolescents, at about age 11 or 12, with XXY syndrome, and if low for age (not all teenage boys with XXY syndrome will have a low level), treatment is started with testosterone on a regular basis. A number of different preparations and delivery methods are available. Testosterone increases facial and body hair, muscle development, sex drive, and may decrease gynecomastia and osteoporosis risk. Boys with XXY syndrome treated with testosterone tend to have higher self-esteem, perhaps because they fit in better with their peers. Attention and concentration may also be improved in these boys. Because low testosterone leads to release of the gonadotropins LH and FSH, these levels are high in untreated individuals with the XXY syndrome.

Once started, monitoring is necessary to watch for possible side effects of testosterone replacement therapy including worsening acne, too rapid sexual development, and behavior problems, especially aggression. Prostate enlargement may also be a side effect of testosterone therapy. Testosterone therapy does not change the rate of infertility. Genetic counselors or endocrinologists may discuss the option of semen collection and sperm-banking (cryopreservation) in XXY individuals during puberty.

Treatment for associated conditions (osteoporosis, developmental delay, breast cancer, varicose veins, lung disease, diabetes, etc.) will depend upon the severity of the condition.

Individuals and their families may need help with adjusting to this condition. Some boys or young men will be very concerned about the risk of infertility; it is important to validate and address this concern. Some boys will be embarrassed about having an “extra” X chromosome and may feel this makes them less male or partially female. However, XXY syndrome is not an intersex condition and does not lead to an increased likelihood for males to identify as females.

Boys with XXY may be withdrawn socially and may need social skills training. They may need special education services or provisions in an individualized educational plan for learning problems. Sometimes, having a genetic diagnosis can help children receive these services.

New methods of sperm extraction, sometimes combined with intracytoplasmic sperm injection, may allow males with XXY syndrome to biologically father children.

All children who have been born after conception using sperm extraction have had a normal karyotype. However, certain fertility treatments may be associated with a slightly increased risk for sex chromosome differences. This will be discussed by the specialist prior to treatment.