title: Clinical review: Klinefelter syndrome--a clinical update.
abstract: BACKGROUND
  Recently, new clinically important information regarding Klinefelter syndrome (KS) has been published. We review aspects of epidemiology, endocrinology, metabolism, body composition, and neuropsychology with reference to recent genetic discoveries.
  
  
  METHODS
  PubMed was searched for "Klinefelter," "Klinefelter's," and "XXY" in titles and abstracts. Relevant papers were obtained and reviewed, as well as other articles selected by the authors.
  
  
  RESULTS
  KS is the most common sex chromosome disorder in males, affecting one in 660 men. The genetic background is the extra X-chromosome, which may be inherited from either parent. Most genes from the extra X undergo inactivation, but some escape and serve as the putative genetic cause of the syndrome. KS is severely underdiagnosed or is diagnosed late in life, roughly 25% are diagnosed, and the mean age of diagnosis is in the mid-30s. KS is associated with an increased morbidity resulting in loss of approximately 2 yr in life span with an increased mortality from many different diseases. The key findings in KS are small testes, hypergonadotropic hypogonadism, and cognitive impairment. The hypogonadism may lead to changes in body composition and a risk of developing metabolic syndrome and type 2 diabetes. The cognitive impairment is mainly in the area of language processing. Boys with KS are often in need of speech therapy, and many suffer from learning disability and may benefit from special education. Medical treatment is mainly testosterone replacement therapy to alleviate acute and long-term consequences of hypogonadism as well as treating or preventing the frequent comorbidity.
  
  
  CONCLUSIONS
  More emphasis should be placed on increasing the rate of diagnosis and generating evidence for timing and dose of testosterone replacement. Treatment of KS should be a multidisciplinary task including pediatricians, speech therapists, general practitioners, psychologists, infertility specialists, urologists, and endocrinologists.
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
authors.forename: Kristian A
authors.initials: KA
authors.lastname: Groth
authors.forename: Anne
authors.initials: A
authors.lastname: Skakkebæk
authors.forename: Christian
authors.initials: C
authors.lastname: Høst
authors.forename: Claus Højbjerg
authors.initials: CH
authors.lastname: Gravholt
authors.forename: Anders
authors.initials: A
authors.lastname: Bojesen
mesh_terms: D001823:Body Composition / Q000502:physiology; D005820:Genetic Testing; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007713:Klinefelter Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology* / Q000628:therapy*; D008297:Male; D008954:Models, Biological; D010809:Physical Fitness / Q000502:physiology; D010902:Pituitary Gland / Q000502:physiology; D013737:Testis / Q000502:physiology
chemical_list: D005947:Glucose