Klinefelter Syndrome
Klinefelter syndrome, or 47,XXY, is a common sex chromosome condition in males caused by the presence of an extra X chromosome. It can affect physical, language, and social development, and increases the risk of certain metabolic and autoimmune disorders.
Overview
Klinefelter syndrome, also called 47,XXY, is a chromosomal condition that affects male development. The signs and symptoms vary widely. In some cases, the features are so mild that the condition is not diagnosed until puberty or adulthood. Researchers believe that up to 65 percent of people with Klinefelter syndrome are never diagnosed.
Symptoms and Clinical Features
Physical Characteristics
Individuals with Klinefelter syndrome typically have small testes that produce a reduced amount of testosterone, a condition known as primary testicular insufficiency. A small percentage of affected individuals are born with undescended testes (cryptorchidism). Without treatment, the shortage of testosterone can lead to:
- Delayed or incomplete puberty
- Breast enlargement (gynecomastia)
- Decreased muscle mass
- Decreased bone density
- A reduced amount of facial and body hair
- Fatigue
- Infertility (though up to half of affected individuals may be able to have children using assisted reproductive technologies)
Other physical changes are usually subtle. Most commonly, affected individuals are taller than average—typically 2 to 3 inches taller than would be expected for their family. Other features can include curved pinky fingers, flat feet, and, less commonly, abnormal fusion of certain bones in the forearm (radioulnar synostosis).
Developmental and Cognitive Features
Children with Klinefelter syndrome may experience low muscle tone (hypotonia), difficulty coordinating movements, and mild delays in developmental skills such as rolling over or walking. There is also an increased risk of mild delays in speech and language development.
Affected individuals tend to have better receptive language skills (understanding speech) than expressive language skills (vocabulary and speech production), which can make communication difficult. They also face an increased risk for learning disabilities, most commonly reading problems (dyslexia) and difficulties with written expression. Intellectual disabilities are very rare.
Behavioral and Mental Health Features
Individuals with Klinefelter syndrome may experience anxiety, depression, impaired social skills, or behavioral differences, such as emotional immaturity during childhood or difficulty handling frustration. Affected individuals also have an increased risk for:
- Attention-deficit/hyperactivity disorder (ADHD), typically presenting as problems with attention and distractibility rather than hyperactivity
- Autism spectrum disorder, which affects communication and social interaction
Associated Medical Risks
People with Klinefelter syndrome have an increased risk of developing several health conditions, including:
- Metabolic syndrome: A group of conditions including high fasting blood glucose levels, high blood pressure (hypertension), increased belly fat, and high levels of fats (lipids) such as cholesterol and triglycerides in the blood
- Involuntary trembling (tremors) in the arms or hands
- Breast cancer (if gynecomastia develops)
- Thinning and weakening of the bones (osteoporosis)
- Autoimmune disorders, such as systemic lupus erythematosus and rheumatoid arthritis
Frequency
Klinefelter syndrome affects about 1 in 650 male newborns. It is the most common sex chromosome disorder, which is a group of conditions caused by changes in the number of sex chromosomes (the X and Y chromosomes).
Causes
Klinefelter syndrome is a genetic disorder that results from the presence of an extra X chromosome in cells. Typically, males have one X and one Y chromosome (46,XY). Most often, people with Klinefelter syndrome have one extra X chromosome, for a total of 47 chromosomes (47,XXY). The activity of these extra genes on the X chromosome disrupts development, leading to the characteristic signs and symptoms of the condition.
Mosaic Klinefelter Syndrome
Approximately 10 percent of individuals with Klinefelter syndrome have the mosaic form, known as mosaic Klinefelter syndrome (46,XY/47,XXY). In these individuals, the extra X chromosome is present in only some of their cells, while other cells have the typical 46,XY pattern. People with mosaic Klinefelter syndrome may have milder signs and symptoms, depending on the proportion of cells with the additional chromosome.
Severe Variants
Some conditions caused by the presence of more than one extra sex chromosome in each cell are described as variants of Klinefelter syndrome. These include 48,XXXY syndrome, 48,XXYY syndrome, and 49,XXXXY syndrome. While they also affect male sexual development and cause learning and language delays, their features tend to be more severe, affect more parts of the body, and are classified as separate conditions.
Inheritance
Klinefelter syndrome is not inherited. The addition of an extra X chromosome occurs as a random error called nondisjunction during the formation of reproductive cells (eggs or sperm) in one of the parents. This error prevents X chromosomes from being distributed normally, resulting in an egg or sperm cell with an extra copy of the