Clinical phenotype and management of individuals with mosaic monosomy X with Y chromosome material stratified by genital phenotype

Am J Med Genet A. 2021 May;185(5):1437-1447. doi: 10.1002/ajmg.a.62127. Epub 2021 Feb 22.

Abstract

Individuals mosaic for monosomy X and a cell line with Y chromosome material can have genitalia that appear phenotypical female, male, or ambiguous. Those with this karyotype and typical female genitalia are diagnosed with Turner syndrome; however, this definition specifically excludes those with genitalia other than typical female. There is limited information on whether medical and neurodevelopmental risks are similar among individuals with monosomy X and Y chromosome material across genital phenotypes. This multicenter retrospective study compared comorbidities and clinical management in individuals with monosomy X and Y material and male/ambiguous genitalia to those with typical female genitalia. Electronic medical records for all patients with monosomy X and Y material (n = 76) at two large U.S. pediatric centers were abstracted for predetermined data and outcomes. Logistic regression was used to compare the two phenotypic groups adjusting for site and duration of follow-up. The male/ambiguous genitalia group was just as likely to have congenital heart disease (RR 1.0, 95%CI [0.5-1.9]), autoimmune disease (RR 0.6 [0.2-1.3]), and neurodevelopmental disorders (RR 1.4 [0.8-1.2]) as those with female genitalia. Despite similar risks, they were less likely to receive screening and counseling. In conclusion, individuals with monosomy X and Y chromosome material have similar medical and neurodevelopmental risks relative to individuals with Turner syndrome regardless of genitalia, but there are notable differences in clinical management.

Keywords: 45,X/46,XY; Turner syndrome; mixed gonadal dysgenesis; monosomy X; mosaicism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Child
  • Chromosomes, Human, Y / genetics
  • Disorders of Sex Development / genetics*
  • Disorders of Sex Development / pathology
  • Female
  • Genitalia / growth & development
  • Genitalia / pathology
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotype
  • Male
  • Monosomy / genetics*
  • Monosomy / pathology
  • Mosaicism
  • Phenotype
  • Sex Chromosome Aberrations*
  • Turner Syndrome / genetics*
  • Turner Syndrome / pathology