Clinical genetics of Kallmann syndrome

Ann Endocrinol (Paris). 2010 May;71(3):149-57. doi: 10.1016/j.ando.2010.02.005. Epub 2010 Apr 2.


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 (KAL1). 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 (KAL2). 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 autosomal recessive monogenic (KAL3) and digenic/oligogenic KS transmission modes. 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. Notably, KS may also be part of pleiotropic developmental diseases including CHARGE syndrome; this disease results in most cases from neomutations in CHD7 that encodes a chromodomain helicase DNA-binding protein.

Publication types

  • Review

MeSH terms

  • Abnormalities, Multiple / genetics
  • Estrogen Replacement Therapy / methods
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Germ-Line Mutation
  • Humans
  • Hypogonadism / drug therapy
  • Hypogonadism / genetics
  • Hypogonadism / physiopathology
  • Kallmann Syndrome / genetics*
  • Kallmann Syndrome / physiopathology
  • Mutation
  • Mutation, Missense
  • Nerve Tissue Proteins / genetics*
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics*


  • ANOS1 protein, human
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1