The Genetics of Hypogonadotropic Hypogonadism

Balasubramanian Bhagavath; Lawrence C. Layman

doi:10.1055/s-2007-980221

Seminars in Reproductive Medicine, Inhaltsverzeichnis

Semin Reprod Med 2007; 25(4): 272-286
DOI: 10.1055/s-2007-980221

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

Abstract

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