Context: Growth is a highly complex process regulated by the interaction between sex steroids and the growth hormone IGF-axis. However, other factors such as sex chromosome-related genes play independent roles.

Aim: To evaluate the role of abnormal chromosome constitution for longitudinal growth in relation to reproductive hormones, IGF-I and IGFBP-3.

Setting: Outpatient clinic, Copenhagen University Hospital.

Participants: 86 47,XXY boys, 14 46,XX-males and 9 47,XYY.

Main outcome measures: Standing and sitting height, serum levels of reproductive hormones, IGF-I and IGFBP-3.

Results: In boys with 47,XXY and 47,XYY karyotypes growth was accelerated already in childhood compared to healthy boys.46,XX-males were significantly shorter than healthy boys, but matched the stature of healthy girls. In 47,XXY sitting height/height ratios were lower than expected, whereas body proportions in 46,XX-males and 47,XYY were normal. In all subjects serum levels of IGF-I and IGFBP-3 were within normal limits. The boys with 46,XX and 47,XXY karyotypes presented with low normal testosterone and elevated LH levels after puberty, whereas the sex hormone secretion of the 47,XYY boys remained normal.

Conclusion: We found accelerated growth in early childhood in boys with 47,XXY and 47,XYY karyotypes, whereas 46,XX-males were shorter than controls. These abnormal growth patterns were not reflected in circulating levels of IGF-I and IGFBP-3. The boys with 46,XX and 47,XXY karyotypes developed hypogonadism in puberty, but androgen secretion in 47,XYY boys remained normal. The abnormal stature of these patients may be a result of abnormal gene expression due to the underlying chromosome aberration resulting in excessive expression of growth related genes.