Kallmann syndrome

Eur J Hum Genet. 2009 Feb;17(2):139-46. doi: 10.1038/ejhg.2008.206. Epub 2008 Nov 5.


The Kallmann syndrome (KS) combines hypogonadotropic hypogonadism (HH) with anosmia. This is a clinically and genetically heterogeneous disease. KAL1, encoding the extracellular glycoprotein anosmin-1, is responsible for the X chromosome-linked recessive form of the disease. Mutations in FGFR1 or FGF8, encoding fibroblast growth factor receptor-1 and fibroblast growth factor-8, respectively, underlie an autosomal dominant form with incomplete penetrance. Finally, mutations in PROKR2 and PROK2, encoding prokineticin receptor-2 and prokineticin-2, have been found in heterozygous, homozygous, and compound heterozygous states. These two genes are likely to be involved both in monogenic recessive and digenic/oligogenic KS transmission modes. Notably, mutations in any of the above-mentioned KS genes have been found in less than 30% of the KS patients, which indicates that other genes involved in the disease remain to be discovered.

MeSH terms

  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Humans
  • Kallmann Syndrome / diagnosis
  • Kallmann Syndrome / genetics*
  • Kallmann Syndrome / physiopathology
  • Kallmann Syndrome / therapy
  • Male
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism


  • ANOS1 protein, human
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins