Clinical trial NCT01703676: Epigenetics and Metabolic Disorders in Men With the Klinefelter Syndrome
Official title: Klinefelter Syndrome: Do the Parental Origin and Epigenetic Profile of the Supernumerary X Chromosome Determine Phenotype, Morbidity, Inflammatory Status and Cardiovascular Risk?
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Klinefelter Syndrome, Hypogonadism
Keywords: Hypogonadism, Klinefelter Syndrome, Cardiovascular Risk, Epigenetics, Methylation of Genes
Cardiovascular risk factors
Gonadal status
Gene expression
Methylation
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
First posted: 2012-10-10
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients, their parents, male controls, female controls

Brief summary: This study will elucidate how the parental origin of the X-chromosome influences health status as well as metabolic fate in Klinefelter patients. Epigenetics and transcriptome-research will be directly linked to the metabolic and inflammatory pattern of actual patients to improve care for them. The Klinefelter Syndrome is one of the most common genetic disorders in men. The patients have one supernumerary X-chromosome, which is partly active and disturbs a normal male development. Testosterone deficiency in form of primary hypogonadism is a common feature in these men. Such a condition promotes clinically relevant metabolic patterns related to a pro-inflammatory status and diabetes mellitus type 2 (insulin resis-tance), cardiovascular disease as well as infertility. However, the variety of pathologies is pro-nounced between patients and low testosterone concentrations cannot fully explain the wide scope of pathologies in these men. Some patients become clinically obvious during puberty and adoles-cence, some in their thirties or later and all exhibit a huge variation in phenotype. Switching on and off of specific genes on the X-chromosome is differential, depending on the origin either from the maternal or paternal side. Hence, an influence on the clinical picture is hypothesised. Thus, key targets are clarification of the parental origin of the supernumerary X chromosome and elucidation of methylation and expression profile of pivotal X-chromosomal genes. These will be related to clinically relevant metabolic and inflammatory patterns as well as fertility to identify individual risks as well as treatment strategies for Klinefelter patients.


Eligibility criteria: Inclusion Criteria:

Klinefelter Syndrome

Exclusion Criteria:

Mosaic status

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University Hospital Muenster
name: Michael Zitzmann, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zitzmann M, Bongers R, Werler S, Bogdanova N, Wistuba J, Kliesch S, Gromoll J, Tuttelmann F. Gene expression patterns in relation to the clinical phenotype in Klinefelter syndrome. J Clin Endocrinol Metab. 2015 Mar;100(3):E518-23. doi: 10.1210/jc.2014-2780. Epub 2014 Dec 22.