Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research
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Year : 2011  |  Volume : 133  |  Issue : 1  |  Page : 121-122

Kallmann syndrome and hypogonadotropic hypogonadism

16, LF Tansen Marg, Bengali Market, New Delhi 110 001, India

Date of Web Publication7-Apr-2011

Correspondence Address:
Sangita Yadav
16, LF Tansen Marg, Bengali Market, New Delhi 110 001
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Source of Support: None, Conflict of Interest: None

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How to cite this article:
Yadav S. Kallmann syndrome and hypogonadotropic hypogonadism. Indian J Med Res 2011;133:121-2

How to cite this URL:
Yadav S. Kallmann syndrome and hypogonadotropic hypogonadism. Indian J Med Res [serial online] 2011 [cited 2020 Sep 25];133:121-2. Available from:

Kallmann syndrome and hypogonadotropic hypogonadism, Quiton R, editor (S. Karger, Basel, Switzerland). 2010. 174 pages. Price: US $ 178.00

ISBN 978-3-8055-8617-7

Many basic and clinical researchers have been working in the field of regulatory mechanisms of puberty. Rapid progress has been made in the understanding of the biochemical and molecular mechanisms related to the onset of puberty and its disorders. The author has collected the research done by various working groups, on the hypothalamic pituitary gonadal axis from different parts of the world.

Based on the presence and absence of sense of smell, idiopathic hypogonadotropic hypogonadism (IHH) forms two major subtypes: Kallmann Syndrome (KS) with anosmia/hyposmia and normosomic IHH (nIHH). IHH has served as a neuroendocrine model providing insights into molecular basis of reproductive physiology. Traditionally, IHH has been considered a monogenic disorder but now it is widely appreciated that IHH is characterized by significant heterogeneity.

The various chapters provide detailed information on the discovery and function of the genes implicated in the aetiology of IHH. The first chapter is on Molecular characterization and phenotypic expression of mutations in gene for gonadotropins and their receptors in humans and further discusses their phenotype/genotype correlations of the important gender differences. The second chapter on Role of Kisspeptin/GPR54 (G-protein-coupled-receptor) mutations provides an understanding in the regulation of human puberty development and reproductive function. The subsequent chapter on biology of kisspeptins discusses the physiology and how findings from animal and human studies have provided insight into the understanding of pathophysiology of IHH.

The next chapter highlights the role of fibroblast growth factor (FGF) signaling in gonadotropin-releasing hormone neuronal system (GnRH). The mouse models have shown that FGF signaling is required for olfactory placade induction and differentiation, and the postnatal maintenance of the GnRH neuronal system plays a pivotal role. The subsequent chapter highlights the role of FGFR1 mutations in Kallmann syndrome and the pathogeneses are further discussed with genotype/phenotype correlations. The next chapter discusses the biology of KAL1 and its orthologs: and implications for X linked Kallmann syndrome and the search for novel candidate genes. Chapter 7 on Biological actions and interactions of anosmin1 highlights the pleiotropic role in neuronal development, migration and organogenesis.

The authors have proposed that the signaling network of anosmin1 shall pave the way forward in understanding the molecular pathogenesis of KS. The understanding of normosomic IHH and the genotype and phenotype of patients with GnRHR mutations has been discussed in chapter 8. It has been recently demonstrated that the GnRH 1 mutations might also cause human congenital IHH. Mutations in the prokineticin 2 peptide (PROK2) and its transmembrane domain type 2 receptor (PROKR2) are newly identified molecular culprits in autosomal KS. The pathophysiology and genotype-phenotype correlations are discussed in chapter 9. These observations point towards a combination of Mendelian autosomal recessive transmission, with more complex oligogenic transmission. In Chapter 10, the authors review the genetics of neurokinin B and its receptor and their role in the regulation of human GnRH secretion in hypogonadotropic hypogonadism (HH). There is a chapter on Rarer syndromes characterized by features of endocrinopathies along with HH and physical changes, e.g. Prader Willi Syndrome, CHARGE syndrome, Bardet-Biedl syndrome, congenital adrenal hyperplasia, DAXI and leptin deficiency, etc. highlighting mutation defects.

The authors in the chapter on Complex genetics in IHH describe that it is a potentially oligogenic disease, which influences the genetic predisposition and clinical course. The hormonal and/or environmental factors along with epigenetic factors and involvement of multiple genes may elucidate the disease pathogenesis. In the last chapter the authors have concluded that the studies in humans with GnRH deficiency and animal models with HH are unraveling the fascinating ontogeny of GnRH neurons and the last decade has witnessed discovery of a number of novel genes that are implicated in human GnRH deficiency. The prismatic human model of GnRH deficiency presents with an opportunity to unravel the molecular basis of the arousal of puberty in humans.

The identification of a wide range of mutations in the genes encoding the two gonadotropins leutinizing hormone and follicle stimulating hormone and their respective receptors have provided invaluable insight into their physiological role in gender determination, pubertal development and the acquisition of full fertility potential. KS patients represent a unique human model that provides insights into signaling factors involved in the organization of a critical neuroendocrine system.

The growing genetic, clinical and molecular complexity of HH now warrants an integrated investigatory approach, with phenotyping of GnRH deficient subjects, using next generation gene sequencing to aid novel gene discovery and bioinformatics to expand the biology of the evolving pathways.

This book enlightens the physicians, padiatricians, endocrinologists, and makes them traverse towards the path of precise biological basis of the onset of human puberty which is one of the unanswered questions. The book is useful for those working in this field from basic sciences.


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