- Article Original
- Endocrinologie
- Published:
Le syndrome de kallmann de morsier aspect génétique
Kallmann syndrome. Genetic aspect
Andrologie volume 18, pages 127–130 (2008)
Resume
Le syndrome de Kallmann De Morsier (SK) représente une affection rare; essentielle cause de déficit gonadotrope congénital, il associe un hypogonadisme à une anosmie (ou hyposmie) et à un certain nombre d’autres manifestations cliniques telles les syncinésies d’imitation ou mouvements en miroir, l’atteinte rénale et urologique, les anomalies neurosensorielles et de la ligne médiane.
Au plan génétique, la mutation du gène kal-1 est responsable de la forme liée à l’X du SK, et ce n’est qu’en 2003 que le gène du récepteur du « fibroblast growth factor » ou FGFR1, responsable d’une des formes autosomiques du SK, a été identifié.
Deux autres gènes ont été récemment identifiés, le gène de la prokinécitine 2 (PROK2) et son récepteur de type 2 (PROK2R2); le gène Neuropiline 2 est par ailleurs considéré comme candidat du SK.
Le but de ce travail est de traiter les particularités génétiques du SK, lesquelles sont essentielles à la compréhension de cette affection restée longtemps inconnue.
Abstract
Kallmann syndrome (KS) is a rare, heterogeneous disorder consisting of congenital hypogonadotropic hypogonadism, associated with anosmia (or hyposmia) and other clinical manifestations such as mirror movements, and renal, urological and neurosensory disorders.
The presence of anosmia with micropenis in boys is suggestive of the diagnostic of KS. In KS, the GnRH neurons do not migrate correctly from the olfactory placode to the hypothalamus during development and olfactory bulbs also fail to form, leading to anosmia.
Mutations in KAL1 which encodes Anosmin-1, are responsible for the X-linked form of KS. Anosmin-1 is normally expressed in the brain, facial mesenchyme, mesonephros and metanephros. It is required to promote migration of GnRH neurons into the hypothalamus. It also allows migration of olfactory neurons from the olfactory bulbs to the hypothalamus.
The loss of function mutations in FGFR1 “fibroblast growth factor” were identified in 2003 as a cause of autosomal forms of this disease.
An additional autosomal cause of Kallmann syndrome was recently identified by a mutation in the prokineticin receptor-2 gene (PROKR2) (KAL-3) and its ligand prokineticin 2 (PROK2) (KAL-4). Mutations in these genes induce various degrees of olfactory and reproductive dysfunction, but not the other symptoms seen in KAL-1 and KAL-2 forms of KS.
Neuropilin2, which has an important role in migration of GnRH neurons, is a recent candidate gene for KS.
The authors describe the genetic features and recent findings of KS, necessary to understand this disease.
References
BOULOUX P.M., YOULI H.U., MAC COLL G.: Recent advances in the pathogenesis of Kallmann’s syndrome. Progress in brain research. New-York, Elsevier Science B.V., 2002.
CARIBONI A., HICKOK J., RAKIC S. et al.: Neuropilin-2 and its ligands are involved in the migration of GnRH-secreting neurons. J. Neurosci., 2007, 27: 2387–2395.
DODÉ C., HARDELIN J.P.: Syndrome de Kallmann De Morsier, insuffisance de signalisation par les FGF? Médecine Sciences, 2004, 20: 8–9.
DODÉ C., LEVILLIERS J., DUPONT J.M. et al.: Loss of function mutations in FGFR1 causes autosomal dominant Kallmann syndrome. Nat. Genet., 2003, 33: 463–465.
DODÉ C., TEIXEIRA L., LEVILLIERS J. et al.: Kallmann Syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet., 2006, 2: e175.
FRANCO B., GUIOLI S., PRAGLIOLA A. et al.: A gene deleted in Kallmann’s syndrome shares homology with neural cell adhesion and axonal path finding molecules. Nature, 1991, 353: 529–536.
HARDELIN J.P., KARYN JULLIARD A., MONIOT B. et al.: Anosmine-1 is a regionally restricted component of basement membranes and interstitial matrices during organogenesis: implication for the developmental anomalies of X chromosome-linked Kallmann syndrome. Dev. Dyn., 1999, 44: 215–226.
HARDELIN J.P., LEVILLIERS J., BLANCHARD S. et al.: Heterogeneity in the mutations resposible for X chromosome-linked Kallmann syndrome. Hum. Mol., Genet., 1993, 2: 373–377.
HEBERT J.M., PARTANEN J., ROSSANT J., MCCONNELL S.K.: FGF signaling through FGFR1 is required for olfactory bulb morphogenesis. Development, 2003, 130: 1101–1111.
KALLMANN F.J., SCHOENFELD W.A.: The genetic aspects of primary eunuchoidism. Am. J. Mental Deficiency, 1944, XLVIII: 203–236.
MATSUMOTO S., YAMAZAKI C, MASUMOTO K. et al.: Abnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2. Proc. Natl Acad. Sci. USA, 2006, 103: 4140–145.
PITTELOUD N., MEYSING A., QUINTON R. et al.: Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes. Mol. Cell. Endocrinol., 2006, 254–255: 60–69.
PITTELOUD N., ZHANG C., PIGNATELLI D. et al.: Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc. Natl Acad. Sci. USA. 2007, 104: 17447–17452.
SATO N., KATSUMATA N., KAGAMI M. et al.: Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast gowth factor receptor 1 (FGFR1 or KAL 2) in five families and 18 sporadic patients. J. Clin. Endocrinol. Metab., 2004, 89:1079–1088.
SEMINARA S.B., HAYES F.J., CROWLEY W.F.: Gonadotropin-releasing hormone deficiency in the human: pathophysiological and genetic considerations. Endocrine Reviews, 1998, 19: 521–539.
SHWANZEL-FUDUKA M., BICK D., PFAFF D.W.: Luteinizing hormone-releasing hormone (LHRH) expressing cells do not migrate normally in an inherited hypogonadal (Kallmann) syndrome. Mol. Brain Res., 1989, 6: 311–326.
WALDSTREICHER J., SEMINARA S.B., JAMESON J.L et al.: The genetic and clinical heterogeneity of gonadotropin-releasing hormone deficiency in the human. J. Clin. Endocrinol. Metab., 1996, 81:4388–4395.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
El Ansari, N. Le syndrome de kallmann de morsier aspect génétique. Androl. 18, 127–130 (2008). https://doi.org/10.1007/BF03040390
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03040390