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Genetics of Delayed Puberty

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Pituitary Disorders of Childhood

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

The pathogenesis of delayed puberty (DP) encompasses several conditions including functional hypogonadism, most commonly due to self-limited (also known as constitutional) DP, GnRH deficiency leading to hypogonadotropic hypogonadism, and disorders causing primary hypogonadism. Whilst many of the genetic defects responsible for the latter two groups have been identified in the last decade, the genetic basis of self-limited DP remains to a great degree an unsolved mystery. Self-limited DP is a highly heritable trait, which often segregates in an autosomal dominant pattern; however, its neuroendocrine pathophysiology and genetic regulation remain unclear. Some insights into the genetic mutations that lead to familial DP have come from sequencing genes known to cause GnRH deficiency, most recently via next-generation sequencing and others from large-scale genome-wide association studies in the general population. Results of these studies suggest that a variety of different pathogenic mechanisms affecting the release of the puberty ‘brake’ can lead to self-limited DP. These include abnormalities of GnRH neuronal development and function, GnRH receptor and LH/FSH abnormalities, metabolic and energy homeostasis derangements and transcriptional regulation of the HPG axis. Thus, genetic causes of DP may have effects as early as in foetal life, throughout early childhood, and on into adolescence.

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  1. Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK

    Sasha Howard

  2. Paediatric Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK

    Leo Dunkel

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    Brenda Kohn

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Howard, S., Dunkel, L. (2019). Genetics of Delayed Puberty. In: Kohn, B. (eds) Pituitary Disorders of Childhood. Contemporary Endocrinology. Humana Press, Cham. https://doi.org/10.1007/978-3-030-11339-1_13

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