[Kallmann syndrome: a historical [corrected] clinical and molecular review].
Kallmann syndrome (KS), the association of hypogonadotropic hypogonadism and anosmia, was described by Maestre de San Juan in 1856 and characterized as a hereditary condition by Franz Josef Kallmann in 1944. Many aspects such as pathogeny, phenotype and genotype in KS were described in the last fifteen years. The knowledge of this condition has grown fast, making it difficult to update. Here we review historical aspects of this condition and its discoverers and describe new findings regarding the embryogenesis of the olfactory bulb and GnRH secreting neuronal tracts that are important for understanding the association of hypogonadism and anosmia. Additionally, we describe the phenotypic and genotypic heterogeneity of KS, including five related genes (KAL-1, FGFR1, PROKR2, PROK2 e NELF), and discuss the function of each codified protein in migration and maturation of the olfactory and GnRH neurons, with data from in vitro and in vivo studies. Finally we describe the clinical phenotype of patients carrying these mutations.
Ribeiro
Rogério Silicani
RS
Unidade de Neuroendocrinologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, SP, Brazil.
Abucham
Julio
J
D016326:Extracellular Matrix Proteins / Q000235:genetics; D005768:Gastrointestinal Hormones / Q000235:genetics; D018740:Genetic Heterogeneity; D005838:Genotype; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics; D006801:Humans; D017436:Kallmann Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics; D000857:Olfaction Disorders / Q000235:genetics; D009830:Olfactory Bulb / Q000502:physiology; D009833:Olfactory Pathways / Q000502:physiology*; D055696:Olfactory Perception; D010641:Phenotype; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics
C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D005768:Gastrointestinal Hormones; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C423608:PROK2 protein, human; C470838:PROKR2 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D007987:Gonadotropin-Releasing Hormone; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1