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Le syndrome de kallmann de morsier aspect génétique

Kallmann syndrome. Genetic aspect

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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.

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Correspondence to Nawal El Ansari.

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El Ansari, N. Le syndrome de kallmann de morsier aspect génétique. Androl. 18, 127–130 (2008) doi:10.1007/BF03040390

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Mote clés

  • hypogonadisme hypogonadotrophique
  • syndrome de Kallmann
  • anosmie
  • aspect génétique

Key words

  • hypogonadotropic hypogonadism
  • Kallmann syndrome
  • anosmia
  • genetic features