Mental development in polysomy X Klinefelter syndrome (47,XXY; 48,XXXY): effects of incomplete X inactivation

Semin Reprod Med. 2001 Jun;19(2):193-202. doi: 10.1055/s-2001-15400.


The child with XXY or a variant form is a fertile ground for scientific investigation because of the homogeneity of the disorder and the increased prevalence of learning disorders associated with it. However, the research studies of boys with XXY (Klinefelter syndrome) have been plagued by a variety of factors from small sample size, methodological flaws, and ascertainment bias. In spite of these shortcomings, there remains some consistency to the neurobehavioral profile of this disorder. In general, the prenatal population of boys with XXY is less affected developmentally and is more academically successful than the boys identified through postnatal diagnosis. Boys with XXY often have decreased muscle tonus, delayed speech, and language skills with an increased incidence of reading differences and dyslexia. It does appear that social difficulties may be mediated by language processing problems and temperamental issues. The neurobehavioral and neurocognitive phenotype of boys with XXY places them at risk for school failure and secondary behavioral disturbances. Therefore, early evaluation and intervention is strongly recommended since the prognosis may be improved significantly with appropriate therapeutic intervention. The natural history of this disorder is not well defined from the neurodevelopmental, neuroimaging, and cytogenetic perspective. Further investigation into the effects and the relationships between parental origin and outcome may provide many answers regarding the variability of the disorder. Lastly, some promising theories have been postulated regarding the neurobiological etiology of this disorder, which requires more investigation if we are to understand the pathogenesis of this XXY and its effect on learning.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Aneuploidy
  • Child
  • Dosage Compensation, Genetic*
  • Humans
  • Klinefelter Syndrome / genetics*
  • Klinefelter Syndrome / physiopathology*
  • Learning Disabilities / genetics*
  • Learning Disabilities / physiopathology*
  • Male
  • Mosaicism / genetics
  • Motor Skills Disorders / genetics
  • Motor Skills Disorders / physiopathology
  • X Chromosome / genetics*