Neurodevelopmental outcome of prenatally diagnosed boys with 47,XXY (Klinefelter syndrome) and the potential influence of early hormonal therapy

Am J Med Genet A. 2020 Aug;182(8):1881-1889. doi: 10.1002/ajmg.a.61561. Epub 2020 Mar 27.

Abstract

This cross-sectional study examined the neurodevelopment of a large, prenatally diagnosed population of boys with 47,XXY; investigated the potentially positive effects of early hormonal therapy (EHT) on language, cognition, and motor in this population; and identified novel at risk biomarkers associated with 47,XXY. Two-hundred and seventy two evaluations were collected from 148 prenatally diagnosed boys with 47,XXY between 0 and 36 months and separated into one of three groups, depending on visit age: Y1 (0-12 months; n = 100), Y2 (13-24 months; n = 90), and Y3 (25-36 months; n = 82). Those who received EHT (administered by 12 months) were further separated (Y1, n = 37; Y2, n = 34; Y3, n = 30). Neurodevelopmental evaluations consisted of Preschool Language Scales, Early Language Milestone Scale, and Bayley Scales of Infant and Toddler Development and evaluated the effect of EHT on auditory comprehension, expressive communication, receptive language, cognition, and motor. EHT was found to be associated with a positive effect within the first year of life in these domains, as well as in the second and third year of life. Additionally, three novel at-risk biomarkers were identified in this cohort: feeding difficulties in infancy, positional torticollis, and the need for orthotics. The positive effects of EHT observed in language, cognition, and motor at variable stages within the first 3 years of life provide additional evidence into the possible efficacy of early biological treatment for boys with 47,XXY to address the neurodevelopmental dysfunction.

Keywords: 47,XXY; Klinefelter syndrome; early hormonal therapy; neurodevelopment; prenatally diagnosed.

MeSH terms

  • Biomarkers / blood
  • Child, Preschool
  • Cognition / drug effects
  • Cognition / physiology
  • Female
  • Hormones / administration & dosage*
  • Hormones / adverse effects
  • Humans
  • Infant
  • Klinefelter Syndrome / diagnosis
  • Klinefelter Syndrome / drug therapy*
  • Klinefelter Syndrome / genetics
  • Klinefelter Syndrome / physiopathology
  • Male
  • Neurodevelopmental Disorders / diagnosis
  • Neurodevelopmental Disorders / epidemiology
  • Neurodevelopmental Disorders / genetics
  • Neurodevelopmental Disorders / physiopathology
  • Pregnancy
  • Prenatal Diagnosis*
  • Risk Factors
  • Sex Chromosome Disorders / diagnosis
  • Sex Chromosome Disorders / drug therapy*
  • Sex Chromosome Disorders / genetics
  • Sex Chromosome Disorders / physiopathology
  • XYY Karyotype / diagnosis
  • XYY Karyotype / drug therapy*
  • XYY Karyotype / genetics
  • XYY Karyotype / physiopathology

Substances

  • Biomarkers
  • Hormones

Supplementary concepts

  • 47, XYY syndrome