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Klinefelter’s syndrome is the presence of an extra X chromosome in males to give (47,XXY). Sometimes it may also be (48, XXYY) or (49, XXXY). Occasionally there is mosaicism with some cells having 46, XY and some having 47, XXY. Symptoms are generally most severe in cases of 49, XXXY and least severe in those with mosaicism.
Klinefelter’s Syndrome is named after Dr Harry Klinefelter at Massachusetts General Hospital in the 1940s who described a series of patients with a specific set of clinical features:
- Tall height
- Small testes
- Unable to produce sperm
- Gynaecomastia
- Little facial or body hair
- There may also be learning disability in more severe cases
Epidemiology
- 1 in 660 male live births
- The most common sex chromosome disorder
- Often is goes undiagnosed, or is not diagnosed until adulthood – for example when conducting fertility testing for a couple who are struggling to conceive
Clinical features
- Clumsyness
- Learning difficulties (usually mild)
- Typically intellectual ability is reduced y 10-20 IQ points, but still within the normal range. More susceptible to behavioural and psychological problems.
- Self obsessed behaviour
Adults
- Taller than average
- Long legs
- Narrow shoulders
- Wide hips
- Long limbs
- Gynaecomastia + Infertility + small soft testes (Hypogonadism) (30% of cases)
- Testes are typically small and firm
- Limited libido
- Erectile dysfunction
- ↑ Risk of
- Most patients are infertile – there is a lack of sperm in the semen (azoospermia)
Investigations
- Can be diagnosed antenatally with amniocentesis or chorionic villus sampling
- Reproductive hormonal panel may be abnormal
- Testosterone ↔ or ↑
- FSH ↑
- LH ↑
- Diagnosis is confirmed by chromosomal analysis (karyotyping)
Complications and associations
Klinefelter’s syndrome is associated with increased risk for several other disorders, including:
- Endocrine abnormalities – diabetes, hypothyroidism, hypoparathyroidism, early (precious) puberty
- Autoimmune disease – SLE, rheumatoid arthritis
- Osteoporosis
- Cardiovascular disease – increased risk
- Male Breast cancer
- Increased risk of testicular cancer
- Increased risk of PE / DVT
- Increased risk of leukaemia
- Increased risk of psychiatric disorders
- Increased risk of autism
- Developmental delay
The average lifespan is slightly less than the general population – by around 2 years – usually due to the increased incidence of the above associated diseases.
Treatment
Testosterone – is often given from puberty onwards, and helps the development of secondary sexual characteristics. It also reduces the long-term risk of many of the long term complications and associations.
However, puberty is often normal in most cases.
- Also helps to increase muscle mass and increase growth of facial hair and body hair
- Injection of sperm into the egg has reportedly been successful
Plastic surgery
- May be performed for gynaecomastia
Cytogenetics
- Extra X chromosome
- Equal chance of inheritance from mother or father
- Maternal cases often associated with advancing maternal age
- Small proportion of cases are due to mosaicism
- >2 X chromosomes are sometimes present. These cases are associated with more severe learning difficulties, and more pronounced features of Klinefelter’s.