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International Journal of Endocrinology
Volume 2014, Article ID 649154, 13 pages
Review Article

Central Hypogonadotropic Hypogonadism: Genetic Complexity of a Complex Disease

1Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, NOCSAE, Via Pietro Giardini 1355, 41126 Modena, Italy
2Center for Genomic Research, University of Modena and Reggio Emilia, Via Giuseppe Campi 187, 41125 Modena, Italy
3Azienda USL of Modena, Via San Giovanni del Cantone 23, 41121 Modena, Italy

Received 24 June 2014; Revised 22 August 2014; Accepted 22 August 2014; Published 1 September 2014

Academic Editor: Michael Horowitz

Copyright © 2014 Marco Marino et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Central hypogonadotropic hypogonadism (CHH) is an emerging pathological condition frequently associated with overweight, metabolic syndrome, diabetes, and midline defects. The genetic mechanisms involve mutations in at least twenty-four genes regulating GnRH neuronal migration, secretion, and activity. So far, the mechanisms underlying CHH, both in prepubertal and in adulthood onset forms, remain unknown in most of the cases. Indeed, all detected gene variants may explain a small proportion of the affected patients (43%), indicating that other genes or epigenetic mechanisms are involved in the onset of CHH. The aim of this review is to summarize the current knowledge on genetic background of CHH, organizing the large amount of data present in the literature in a clear and concise manner, to produce a useful guide available for researchers and clinicians.