title: Clinical, endocrinological, and epigenetic features of the 46,XX male syndrome, compared with 47,XXY Klinefelter patients.
abstract: BACKGROUND
  The 46,XX male syndrome represents a rare, poorly characterized form of male hypogonadism.
  
  
  OBJECTIVE
  The objective of the study was to distinguish the 46,XX male syndrome from the more frequent 47,XXY-Klinefelter syndrome in regard to clinical, hormonal, and epigenetic features.
  
  
  METHODS
  This was a case-control study.
  
  
  METHODS
  The study was conducted at a university-based reproductive medicine and andrology institution.
  
  
  METHODS
  Eleven SRY-positive 46,XX males were compared with age-matched controls: 101 47,XXY Klinefelter patients, 78 healthy men, and 157 healthy women [latter all heterozygous for androgen receptor (AR) alleles].
  
  
  METHODS
  There were no interventions.
  
  
  METHODS
  There was a comparison of phenotype, endocrine profiles, and X-chromosomal inactivation patterns of AR alleles.
  
  
  RESULTS
  The 46,XX males were significantly smaller than Klinefelter patients or healthy men, resembling female controls in height and weight. The incidence of maldescended testes was significantly higher than that in Klinefelter patients and controls. Gynecomastia was more frequent in comparison with controls, whereas there was a nonsignificant trend in comparison with Klinefelter patients. All XX males were infertile and most were hypogonadal. The inactivation patterns of AR alleles in XX males were significantly more skewed than in Klinefelter patients and women. Seven of 10 heterozygous XX male patients displayed an extreme skewing of more than 80% with no preference toward the shorter or longer AR allele. The length of the AR CAG repeat polymorphism was positively related to traits of hypogonadism.
  
  
  CONCLUSIONS
  XX males are distinctly different from Klinefelter patients in terms of clinical and epigenetic features. Nonrandom X chromosome inactivation ratios are common in XX males, possibly due to the translocated SRY gene. The existence of a Y-chromosomal, growth-related gene is discussed.
authors.affiliation: Institute of Reproductive Medicine, University Clinics of Münster, D-48129 Münster, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Vorona
authors.forename: Michael
authors.initials: M
authors.lastname: Zitzmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Gromoll
authors.forename: Andreas N
authors.initials: AN
authors.lastname: Schüring
authors.forename: Eberhard
authors.initials: E
authors.lastname: Nieschlag
mesh_terms: D000293:Adolescent; D000328:Adult; D001772:Blood Cell Count; D016022:Case-Control Studies; D044127:Epigenesis, Genetic; D005260:Female; D023961:Gonadal Dysgenesis, 46,XX / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007713:Klinefelter Syndrome / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011944:Receptors, Androgen / Q000235:genetics; D013577:Syndrome; D018911:Trinucleotide Repeats
chemical_list: D011944:Receptors, Androgen