XXY – Klinefelter Syndrome

Klinefelter Syndrome is a common chromosomal variation. It is also known as 47,XXY, XXY Syndrome or XXY. On this site we use the terms interchangeably.

In most individuals there are 46 chromosomes, arranged as XY or XX. When a person is born with an extra sex chromosome (known as the X or Y chromosome) it is called a sex chromosome variation or anomaly. A person with Klinefelter Syndrome (KS) has an extra X chromosome to make up the genetic profile 47, XXY. The majority of individuals will have the extra X chromosome in all their cells but 15% to 20% of KS individuals are mosaics usually with 2 cell lines 47, XXY/46, XY. This essentially means that the extra X is in some of their body cells but not all of them.

Klinefelter syndrome (KS) was first described by Harry F. Klinefelter in 1942. He reported 9 men with testicular abnormalities who failed to produce sperm and had gynecomastia. In 1959, this was found to be the result of an additional X chromosome.

• Who is affected
• Causes
• Signs and symptoms
• Misconception
• Diagnosis
• Treatment
  

Who is affected?

Klinefelter Syndrome/XXY is the most common chromosome disorder in males in which the predicted incidence is as high as 1 in 450 male births. This makes it one of the most common chromosomal variations. However, it’s estimated that up to 75% of cases are undiagnosed or misdiagnosed. Whilst it is widely documented that only males are affected by KS/XXY, there are 13 reported and documented cases of females born with 47, XXY. Research suggests that there are two reasons for this. It is believed that many females that are born with 47, XXY also have complete androgen insensitivity syndrome (CAIS). Individuals with CAIS are typically genetically male but their body is unable to respond to certain male sex hormones (called androgens). As a result, they may have mostly female sex characteristics, or signs of both male and female sexual development. Given that a 47, XXY karyotype is not a rare finding, it is possible for people to have this karyotype as well as CAIS. Other research has identified that females with 47,XXY were found to be missing the SRY gene on their Y chromosome (called SRY negative). The SRY gene provides instructions for a protein that causes a fetus to develop as male. If a person is missing the SRY gene, they will develop as female. This can occur in people with a 46, XY male karyotype, as well. It is important to note that some individuals with a 47,XXY karyotype don’t necessarily identify as males.

Causes

While the cause of Klinefelter syndrome is genetic, it is not inherited. The chances of subsequent pregnancy with a child with an XXY karyotype are extremely rare. Klinefelter syndrome occurs as the result of a random genetic error during the formation of the egg or sperm or after conception, resulting in a 47, XXY karyotype. The syndrome is not the result of something the parents did or did not do and the reasons behind the formation of an extra X chromosome is unknown. It is congenital, which means it is present from birth.

Signs and Symptoms

Characteristics of Klinefelter syndrome are often subtle, with few noticeable physical signs, consequently, males with this condition are often misdiagnosed or as previously stated go undiagnosed, living their life not realising they have an additional X chromosome. Signs and symptoms of Klinefelter syndrome vary considerably among individuals, there is a broad spectrum of effects and the severity of these effects is vastly different between each individual with Klinefelter syndrome. Some children and individuals experience very few of the potential signs and symptoms and associated health co-morbidities, while other children or individuals are more severely affected and will benefit from early intervention as children and ongoing support as adults, with a good professional health care team. While an individual with Klinefelter Syndrome may have some of these effects, they are very unlikely to have all of them. Most individuals with Klinefelter syndrome lead happy and fulfilling lives. Signs and symptoms of Klinefelter syndrome vary by age. Some effects of Klinefelter Syndrome MAY include:

• Speech and language delays, expressive language disorders
• Learning difficulties, particularly with reading, writing and spelling
• Emotional, social and behavioural challenges
• Cognitive processing challenges, Auditory Processing Disorder
• Autism Spectrum Disorder traits
• Hypogonadism (low levels of testosterone)
• Infertility or lowered fertility
• Increased height
• Fatigue
• Small testicles
• Gynecomastia
• Low muscle tone (hypotonia) – affecting fine and gross motor skills and development
• Concentration/attention challenges and disorders, ADHD
• Sensory processing challenges
• Mental wellbeing concerns including; anxiety, depression and mood disorders
• Health risks including; osteoporosis, diabetes, cardiovascular disorders and some cancers

Diagnosis

Prenatal testing is significantly increasing due to its availability and continued advancements. Many expectant parents are completely unaware that these tests can also identify X & Y sex chromosome variations. These tests can be obtained via analysis of the mother’s blood known as the Harmony test or NIPT. The results can give a percentage of likelihood of an XXY diagnoses. Diagnoses isn’t confirmed until further testing is obtained. The options available are, the analysis of amniotic fluid via amniocentesis or analysis of tissue samples from a portion of the placenta via chorionic villus sampling (CVS). These tests are invasive and can have a small risk of causing a miscarriage. Expectant parents have the option to wait until the baby is born and confirm a diagnosis through the baby’s blood sample. A diagnosis of KS/XXY syndrome in children and adults is often not common and often overlooked, since there is often no medical reason to test for KS/XXY syndrome. Testing is made based upon a thorough clinical evaluation, a detailed patient history, and specialised tests (i.e. chromosomal analysis) that detect the presence of an extra Y chromosome (47,XXY karyotype). The most common type of testing is a specialised blood test known as karyotyping. Children and adults displaying a combination of speech and language delays, motor delays, difficulty particularly with reading, displaying impulsive and challenging behaviour with attention difficulties and have a tall stature should have a blood karyotyping carried out to confirm or rule out a KS/XXY diagnoses. Several adults may only be diagnosed whilst embarking on their journey to have children and there is unexplained fertility challenges.

Treatment

There is no cure for Klinefelter syndrome/XXY. Treatment options can greatly improve some aspects of the condition and help alleviate some of the signs and symptoms and the impacts it can have. Beginning treatment early can greatly increase its effectiveness and positive impacts it has on a child and individuals life. Each individual is different so the treatment needs to be done in a holistic manner in consultation with parents, individuals and the health care team. Some treatment options may include:

• Early intervention, which may include; speech therapy, physical therapy, occupational therapy
• Education support, which may include; additional support at school, learning tools or equipment or adaptive learning techniques
• Behavioural therapy
• Hormone therapy
• Reproductive technologies to aid fertility
• Cosmetic surgery
• Mental health and wellbeing support, which may include; a counsellor, psychologist, OT
• Frequent screening tests and assessments – to ensure the early diagnosis of any associated medical complications.

With proactive management and effective treatment the impacts Klinefelter Syndrome/XXY has on a child and individuals life can be greatly decreased. Most individuals with Klinefelter Syndrome/XXY lead happy and fulfilling lives.

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