The genetics of hypogonadotropic hypogonadism

Semin Reprod Med. 2007 Jul;25(4):272-86. doi: 10.1055/s-2007-980221.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Extracellular Matrix Proteins / genetics
  • Female
  • Genotype
  • Gonadotropin-Releasing Hormone / metabolism*
  • Gonads / metabolism
  • Humans
  • Hypogonadism / genetics*
  • Hypogonadism / metabolism
  • Hypogonadism / physiopathology
  • Hypothalamo-Hypophyseal System / metabolism*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Kallmann Syndrome / genetics*
  • Kallmann Syndrome / metabolism
  • Kallmann Syndrome / physiopathology
  • Male
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Neurons / metabolism
  • Phenotype
  • Puberty / genetics*
  • Puberty, Delayed / genetics
  • Puberty, Delayed / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptors, LHRH / genetics
  • Sex Chromosome Aberrations

Substances

  • ANOS1 protein, human
  • Extracellular Matrix Proteins
  • GNRHR protein, human
  • Nerve Tissue Proteins
  • Receptors, LHRH
  • Gonadotropin-Releasing Hormone
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1