Genetics of pubertal delay

Abstract

The timing of pubertal development is strongly influenced by the genetic background, and clinical presentations of delayed puberty are often found within families with clear patterns of inheritance. The discovery of the underlying genetic regulators of such conditions, in recent years through next generation sequencing, has advanced the understanding of the pathogenesis of disorders of pubertal timing and the potential for genetic testing to assist diagnosis for patients with these conditions. This review covers the significant advances in the understanding of the biological mechanisms of delayed puberty that have occurred in the last two decades.

Keywords: delayed puberty; hypogonadotropic hypogonadism; puberty.

Figure 1

Secular trend in the mean age of onset of thelarche (A) and of testicular volume >3 ml (B). From Sorensen et al. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Example pedigrees of families with a loss‐of‐function mutation in FGFR1. In these families, individuals carrying the same mutation have a range of clinical phenotypes from Kallmann syndrome, to CHH and isolated DP. CHH, congenital hypogonadotropic hypogonadism. From Boehm et al. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Overlap between genes identified in conditions with central DP. DP, delayed puberty; KS, Kallmann syndrome; nCHH, normosmic congenital hypogonadotropic hypogonadism [Color figure can be viewed at wileyonlinelibrary.com]

Figure 4

The genetic basis of self‐limited DP is related to GnRH neuronal development and function. DP, delayed puberty; GnRH, gonadotropin‐releasing hormone [Color figure can be viewed at wileyonlinelibrary.com]