Early neurodevelopmental and medical profile in children with sex chromosome trisomies: Background for the prospective eXtraordinarY babies study to identify early risk factors and targets for intervention

Am J Med Genet C Semin Med Genet. 2020 Jun;184(2):428-443. doi: 10.1002/ajmg.c.31807. Epub 2020 Jun 7.


Sex chromosome trisomies (SCT), including Klinefelter syndrome/XXY, Trisomy X, and XYY syndrome, occur in 1 of every 500 births. The past decades of research have resulted in a broadening of known associated medical comorbidities as well as advances in psychological research. This review summarizes what is known about early neurodevelopmental, behavioral, and medical manifestations in young children with SCT. We focus on recent research and unanswered questions related to the risk for neurodevelopmental disorders that commonly present in the first years of life and discuss the medical and endocrine manifestations of SCT at this young age. The increasing rate of prenatal SCT diagnoses provides the opportunity to address gaps in the existing literature in a new birth cohort, leading to development of the eXtraordinarY Babies Study. This study aims to better describe and compare the natural history of SCT conditions, identify predictors of positive and negative outcomes in SCT, evaluate developmental and autism screening measures commonly used in primary care practices for the SCT population, and build a rich data set linked to a bank of biological samples for future study. Results from this study and ongoing international research efforts will inform evidence-based care and improve health and neurodevelopmental outcomes.

Keywords: Trisomy X; XXY; XYY; neurodevelopment; testosterone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Child
  • Child, Preschool
  • Chromosomes, Human, X / genetics
  • Female
  • Humans
  • Klinefelter Syndrome / diagnosis*
  • Klinefelter Syndrome / genetics
  • Klinefelter Syndrome / physiopathology
  • Male
  • Neurodevelopmental Disorders / diagnosis
  • Neurodevelopmental Disorders / genetics
  • Neurodevelopmental Disorders / physiopathology
  • Pregnancy
  • Prenatal Diagnosis*
  • Prospective Studies
  • Risk Factors
  • Sex Chromosome Aberrations
  • Sex Chromosome Disorders / diagnosis*
  • Sex Chromosome Disorders / physiopathology
  • Sex Chromosome Disorders of Sex Development / diagnosis*
  • Sex Chromosome Disorders of Sex Development / genetics
  • Sex Chromosome Disorders of Sex Development / physiopathology
  • Sex Chromosomes / genetics
  • Trisomy / diagnosis*
  • Trisomy / genetics
  • Trisomy / physiopathology
  • XYY Karyotype

Supplementary concepts

  • 47, XYY syndrome
  • Triple X syndrome