title: Anthropometry in Klinefelter syndrome--multifactorial influences due to CAG length, testosterone treatment and possibly intrauterine hypogonadism.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Endocrinology and Internal Medicine (MEA) (S.C., A.S., C.T., C.H.G.), Section of Neonatal Screening and Hormones, Department of Clinical Biochemistry (A.C., D.M.H.), Immunology and Genetics, Statens Serum Institute, Center of Functionally Integrative Neuroscience (M.W.), Centre for Rare Diseases, Department of Pediatrics (J.R.Ø.), Department of Psychology and Behavioral Sciences (A.D.P.), Center for Semiotics (M.W.), Aarhus University Hospital, 8000 Aarhus C, Denmark; Department of Clinical Genetics (A.B.), Vejle Hospital, Sygehus Lillebaelt, 7100 Vejle, Denmark; Department of Clinical Genetics (J.M.H.), Odense University Hospital, 5000 Odense, Denmark; Vejleford Rehabilitation Center (A.D.P.), 7140 Stouby, Denmark; and Department of Molecular Medicine (C.H.G.), Aarhus University Hospital, 8200 Aarhus N, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Chang
authors.forename: Anne
authors.initials: A
authors.lastname: Skakkebæk
authors.forename: Christian
authors.initials: C
authors.lastname: Trolle
authors.forename: Anders
authors.initials: A
authors.lastname: Bojesen
authors.forename: Jens Michael
authors.initials: JM
authors.lastname: Hertz
authors.forename: Arieh
authors.initials: A
authors.lastname: Cohen
authors.forename: David Michael
authors.initials: DM
authors.lastname: Hougaard
authors.forename: Mikkel
authors.initials: M
authors.lastname: Wallentin
authors.forename: Anders Degn
authors.initials: AD
authors.lastname: Pedersen
authors.forename: John Rosendahl
authors.initials: JR
authors.lastname: Østergaard
authors.forename: Claus Højbjerg
authors.initials: CH
authors.lastname: Gravholt
mesh_terms: D000293:Adolescent; D000328:Adult; D000886:Anthropometry; D001823:Body Composition / Q000235:genetics; D001837:Body Weights and Measures; D016022:Case-Control Studies; D015984:Causality; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000150:complications*; D007713:Klinefelter Syndrome / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D013739:Testosterone / Q000627:therapeutic use*; D019680:Trinucleotide Repeat Expansion; D055815:Young Adult
chemical_list: D013739:Testosterone