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Semin Reprod Med 2007; 25(4): 272-286
DOI: 10.1055/s-2007-980221
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Genetics of Hypogonadotropic Hypogonadism

Balasubramanian Bhagavath1 , Lawrence C. Layman2
  • 1Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
  • 2Section of Reproductive Endocrinology, Infertility, & Genetics Department of Obstetrics & Gynecology, Reproductive Medicine Program, Developmental Neurobiology Program, The Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia
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Publication History

Publication Date:
26 June 2007 (online)

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ABSTRACT

An up-to-date review of the genetic aspects of idiopathic hypogonadotropic hypogonadism (IHH)/Kallmann syndrome (KS) is presented. Because proper development of the neuroendocrine axis must occur for normal puberty and reproductive function, gonadotropin-releasing hormone (GnRH) neuron migration is outlined first, followed by an introduction to the in vitro analysis of GnRH neuron migration. The normal hypothalamic-pituitary-gonadal (HPG) axis at different ages is discussed, along with a brief overview of normal and delayed puberty in both boys and girls. The phenotype of IHH/KS is discussed in detail, with its relation to Mendelian inheritance and chromosomal translocations. The molecular basis of IHH/KS is reviewed, with particular emphasis on the three most common genes (KAL1, FGFR1, and GNRHR) that possess mutations in these patients. However, all other known genes for which mutations occur are also addressed briefly. The goal of this review is to provide a comprehensive discussion of IHH/KS, and to include both basic science and clinical findings that should allow a more complete understanding of hypothalamic-pituitary neuroendocrinology that is important in puberty and reproduction.

KEYWORDS

Hypogonadism - puberty - genetics

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Lawrence C LaymanM.D. 

Section of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology

The Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-3360

Email: Llayman@mcg.edu

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