Context: Klinefelter syndrome, 47, XXY (KS), is underdiagnosed partly due to few clinical signs complicating identification of affected individuals. Certain phenotypic traits are common in KS. However, not all aspects of the KS phenotype are well described.
Objective: To describe anthropometry and body composition in KS and relate findings to biochemistry and X-chromosome related genetic markers.
Design, setting and participants: Seventy three KS males referred to our clinic and 73 age-matched controls underwent comprehensive measurements of anthropometry and body composition in a cross-sectional, case-controlled study. Furthermore, genetic analysis for parental origin of the supernumerary X-chromosome, skewed X-chromosome inactivation and androgen receptor (AR) CAG repeat length was done.
Main outcome measure: Anthropometry and body composition in KS and the effect of genotype hereon.
Results: KS males were taller (absolute difference: 5.1 cm, P < .001) with longer legs (5.7 cm, P < .001) compared with controls. Furthermore, 2D:4D was increased in KS males (relative effect size: Cohen's d = 0.40), reflecting reduced fetal testosterone exposure. Also, bi-iliac width (0.41), waist (0.52), and hip circumference (0.47) (P < .02 for all), as well as total fat mass (0.74), abdominal fat mass (0.67), and total body fat percentage (0.84) was increased in KS males (P < .001 for all), while bitesticular volume was reduced (4.6). AR CAG repeat length was comparable in KS and controls, and among KS CAG correlated to arm length (P = .04), arm span (P = .01), and leg length (P = .04). Effects of parental origin of the supernumerary X-chromosome and skewed X-chromosome inactivation were negligible.
Conclusions: Anthropometry and body composition in KS is specific and dysmorphic and affected by AR CAG repeat length and decreased exposure to testosterone already during fetal life.
Trial registration: ClinicalTrials.gov NCT00999310.