The cognitive phenotype in Klinefelter syndrome: a review of the literature including genetic and hormonal factors

Dev Disabil Res Rev. 2009;15(4):284-94. doi: 10.1002/ddrr.83.


Klinefelter syndrome (KS) or 47,XXY occurs in approximately 1 in 650 males. Individuals with KS often present with physical characteristics including tall stature, hypogonadism, and fertility problems. In addition to medical findings, the presence of the extra X chromosome can lead to characteristic cognitive and language deficits of varying severity. While a small, but significant downward shift in mean overall IQ has been reported, the general cognitive abilities of patients with KS are not typically in the intellectual disability range. Most studies support that males with KS have an increased risk of language disorders and reading disabilities. Results of other studies investigating the relationship between verbal and nonverbal/spatial cognitive abilities have been mixed, with differing results based on the age and ascertainment method of the cohort studied. Executive function deficits have been identified in children and adults with KS, however, the research in this area is limited and further investigation of the neuropsychological profile is needed. In this article, we review the strengths and weaknesses of previous cognitive and neuropsychological studies in males with KS in childhood and adulthood, provide historical perspective of these studies, and review what is known about how hormonal and genetic factors influence cognitive features in 47,XXY/KS.

Publication types

  • Review

MeSH terms

  • Adult
  • Attention
  • Chromosomes, Human, X / genetics
  • Cognition Disorders / diagnosis
  • Cognition Disorders / epidemiology*
  • Humans
  • Klinefelter Syndrome / epidemiology*
  • Klinefelter Syndrome / genetics*
  • Language Disorders / diagnosis
  • Language Disorders / epidemiology
  • Male
  • Neuropsychological Tests
  • Perceptual Disorders / epidemiology
  • Phenotype*
  • Severity of Illness Index
  • Space Perception
  • Visual Perception
  • Young Adult