Neuropsychologic, Neuroradiologic, Endocrinologic, and Genetic Aspects of Klinefelter Syndrome
Condition: Klinefelter Syndrome
MeSH terms: Klinefelter Syndrome; Syndrome
Study type: Observational

Summary: 
      The purpose of this study is to investigate the following:

        1. Whether Klinefelter Syndrome is associated with altered total and regional brain volumes
           and altered brain activity.

        2. The influence of genetic factors and testosterone treatment on the neuropsychological
           phenotype, total and regional brain volumes and brain activity in men with Klinefelter
           syndrome.
    

Detailed description: 
      Klinefelter syndrome (KS) is the most common sex-chromosome disorder in men with a prevalence
      of 1 in 660 men. Men with the syndrome have an additional X-chromosome. The syndrome is
      associated with cognitive and behavioral dysfunction and also with hypogonadism. Magnetic
      resonance imaging have pointed to different volumetric alterations in several brain
      structures. Several genetic factors involving the X-chromosome have been suggested to
      influence the neuropsychological phenotype in men with KS.

      The aim of this study is to investigate the following: 1.Whether KS is associated with
      altered total and regional brain volumes and altered brain activity. 2.Whether genetic
      factors influence the neuropsychological phenotype, total and regional brain volumes, and
      brain activity in men with KS. 3.Whether testosterone treatment improves cognitive skills and
      change brain activity in men with KS.

      Participants are divided in 5 groups: 1. 50 men with KS who receive testosterone treatment.
      2. 50 men KS who do not receive testosterone treatment. 3. 100 age-matched control men.4. 50
      age-matched control women are included as a control group for X-chromosome inactivation
      pattern. 5. Parents of KS subjects in group 1 and 2 are included to determine the parental
      origin of the supernumerary X-chromosome. Methods include a 3-hour battery of standardized
      neuropsychological tests to cover a broad range of cognitive domains and to assess major
      domains of personality. We use magnetic resonance imaging to measure total and regional brain
      volumes and functional magnetic resonance imaging to measure brain activity while subjects
      are performing a attention-demanding cognitive task. The genetic testing includes the
      parental origin of the supernumerary X-chromosome, the pattern of X-chromosome inactivation,
      androgen receptor (AR) CAGn repeat length, and gene expression profile of brain-expressed
      genes.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Patients with Klinefelter syndrome are recruited from endocrine and fertility clinics.

        The control groups are recruited by advertising for healthy volunteers at the University of
        Aarhus and at the Blood Bank at the Aarhus University Hospital.
      
Biospecimen description: 
      Whole blood, serum, plasma
    
Keywords: Klinefelter syndrome; Neuropsychology; Neuroradiology; Genetics