KLINEFELTER SYNDROME (47,XXY SYNDROME) 

Klinefelter syndrome (47,XXY syndrome) occurs in about 1 in 1,000 male newborns, with 80% having a pure 47,XXY karyotype. The phenotype is variable and can manifest as developmental delay, passivity and learning difficulties in childhood, and leads to hypergonadotropic hypogonadism, underdeveloped secondary sexual characteristics and azoospermia at puberty.

Also called

• 47,XXY syndrome
• XXY syndrome
• XXY trisomy
• Klinefelter's syndrome

Symptoms

The symptoms of Klinefelter syndrome can be mild, meaning some people are not diagnosed until adulthood.

Main symptoms include:

• Abnormal psychomotor development
• Behavior and learning disabilities
• Hypergonadotropic hypogonadism, small testes, low testosterone and azoospermia
• Increased body fat in the trunk
• Delayed puberty
• Enlarged breasts (gynecomastia)

Other symptoms include:

• Taller than average
• Osteoporosis later in life
• Intelligence within the normal range, or 5-10 IQ points below the family average

It is a most common cause of male infertility.

Frequency

The prevalence is approximately 1:1,000 in male newborns. 80% of affected individuals have a pure 47,XXY karyotype, while the remaining 20% have mosaicism or other X polysomies.

Cause

Klinefelter syndrome is a sex chromosome disorder caused by the presence of an extra X chromosome.

Inheritance

Klinefelter syndrome is not inherited.

Screening and diagnosis

Non-invasive prenatal tests (NIPT) can check for genetic conditions of the fetus, including Klinefelter syndrome, before birth with no risk of miscarriage.

Diagnosis is confirmed by karyotype or chromosomal microarray.

Treatment

Testosterone substitution should be performed from puberty where there are subnormal values and for osteoporosis prophylaxis.

References

Ogata et al. 2001, Am J Med Genet 98:353 / Ogata et al. 2001, J Med Genet 38:1

NORD National Organization for Rare Diseases. “47,XXY (Klinefelter Syndrome).” NORD (National Organization for Rare Disorders), 2020, https://rarediseases.org/rare-diseases/47-xxy-klinefelter-syndrome/. Accessed 13 Feb. 2025.

MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2020 Jun 24]. Klinefelter syndrome; [updated 10 Jul. 2023]. Available from: https://medlineplus.gov/genetics/condition/klinefelter-syndrome/. Accessed 13 Feb. 2025.