Increased number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with sex chromosome aneuploidy

Am J Med Genet A. 2010 May;152A(5):1206-12. doi: 10.1002/ajmg.a.33334.

Abstract

Tall stature and eunuchoid body proportions characterize patients with 47,XXY Klinefelter syndrome, whereas patients with 45,X Turner syndrome are characterized by impaired growth. Growth is relatively well characterized in these two syndromes, while few studies describe the growth of patients with higher grade sex chromosome aneuploidies. It has been proposed that tall stature in sex chromosome aneuploidy is related to an overexpression of SHOX, although the copy number of SHOX has not been evaluated in previous studies. Our aims were therefore: (1) to assess stature in 305 patients with sex chromosome aneuploidy and (2) to determine the number of SHOX copies in a subgroup of these patients (n = 255) these patients and 74 healthy controls. Median height standard deviation scores in 46,XX males (n = 6) were -1.2 (-2.8 to 0.3), +0.9 (-2.2 to +4.6) in 47,XXY (n = 129), +1.3 (-1.8 to +4.9) in 47,XYY (n = 44), +1.1 (-1.9 to +3.4) in 48,XXYY (n = 45), +1.8 (-2.0 to +3.2) in 48,XXXY (n = 9), and -1.8 (-4.2 to -0.1) in 49,XXXXY (n = 10). Median height standard deviation scores in patients with 45,X (n = 6) were -2.6 (-4.1 to -1.6), +0.7 (-0.9 to +3.2) in 47,XXX (n = 40), -0.6 (-1.9 to +2.1) in 48,XXXX (n = 13), and -1.0 (-3.5 to -0.8) in 49,XXXXX (n = 3). Height increased with an increasing number of extra X or Y chromosomes, except in males with five, and in females with four or five sex chromosomes, consistent with a nonlinear effect on height.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy*
  • Body Height / genetics*
  • Case-Control Studies
  • Female
  • Gene Dosage / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Nonlinear Dynamics*
  • Polymerase Chain Reaction
  • Sex Chromosome Aberrations*
  • Sex Chromosomes / genetics*
  • Sex Chromosomes / pathology*
  • Short Stature Homeobox Protein

Substances

  • Homeodomain Proteins
  • SHOX protein, human
  • Short Stature Homeobox Protein