Journal of Molecular Medicine

, Volume 82, Issue 11, pp 725–734

Kallmann syndrome: fibroblast growth factor signaling insufficiency?


DOI: 10.1007/s00109-004-0571-y

Cite this article as:
Dodé, C. & Hardelin, JP. J Mol Med (2004) 82: 725. doi:10.1007/s00109-004-0571-y


Kallmann syndrome (KAL) is a developmental disease that combines hypogonadotropic hypogonadism and anosmia. Anosmia is related to the absence or hypoplasia of the olfactory bulbs. Hypogonadism is due to GnRH deficiency and is likely to result from the failed embryonic migration of GnRH-synthesizing neurons. These cells normally migrate from the olfactory epithelium to the forebrain along the olfactory nerve pathway. KAL is phenotypically and genetically heterogeneous. The gene responsible for the X-chromosome linked form of the disease (KAL1) has been identified in 1991. KAL1 encodes anosmin-1, an approx. 95-kDa glycoprotein of unknown function which is present locally in various extracellular matrices during the period of organogenesis. The recent finding that FGFR1 mutations are involved in an autosomal dominant form of Kallmann syndrome (KAL2), combined with the analysis of mutant mouse embryos that no longer express Fgfr1 in the telencephalon, suggests that the disease results from a deficiency in FGF signaling at the earliest stage of olfactory bulb morphogenesis. We propose that the role of anosmin-1 is to enhance FGF signaling and suggest that the gender difference in anosmin-1 dose (because KAL1 partially escapes X-inactivation) explains the higher prevalence of the disease in males.


Kallmann syndrome Anosmin-1 Fibroblast growth factor receptors 



Fibroblast growth factor


Fibroblast growth factor receptor 1


Gonadotropin-releasing hormone


Kallmann syndrome

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Institut Cochin et Laboratoire de Biochimie et Génétique MoléculaireHôpital CochinParisFrance
  2. 2.Unité de Génétique des Déficits Sensoriels, INSERM U587Institut PasteurParis cedex 15France

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