Table 1: Genetic causes of Kallmann’s syndrome (KS) and normosmic isolated hypogonadotropic hypogonadism (IHH).

Gene Gene product Function Inheritance Clinical phenotype Associated clinical phenotype KAL1 Anosmin-1 Cell adhesion X-linked KS Anosmia, bimanual synkinesis, renal agenesis FGFR1 Fibroblast-growth-factor receptor 1 Tyrosine kinase receptor AD KS or IHH Anosmia, cleft lip or palate, ear anomalies, tooth agenesis FGF8 Fibroblast growth factor 8 Ligand of FGFR1 AD KS or IHH NELF Nasal embryonic LHRH factor Neuronal migration AD KS Anosmia CHD7 Chromodomain- helicase-DNA-binding protein 7 DNA-binding protein, neural crest development AD KS or IHH CHARGE syndrome: anosmia, coloboma, heart anomaly, choanal atresia, retardation, ear abnormalities PROKR2 Prokineticin receptor 2 GPCR AD AR KS or IHH Anosmia PROK2 Prokineticin 2 Ligand of PROKR2 AD AR KS or IHH Anosmia WDR11 WD protein Interaction with EMX1 AD KS or IHH Anosmia GPR54/KISS1R Kisspeptin-1 receptor GPCR AR IHH None TACR3 Neurokinin B receptor GPCR AR IHH None TAC3 Neurokinin B Ligand of TACR3 AR IHH None LEPR leptin receptor Single transmembrane-domain receptor AR IHH Obesity LEP leptin Fat-regulating hormone AR IHH Obesity GNRH1 GnRH Release of LH and FSH AR IHH None GNRHR GnRH receptor GPCR AR IHH None LHβ β-subunit of LH Ligand of LH/CG receptor AR IHH None FSHβ β-subunit of FSH Ligand of FSH receptor AR IHH None

GPCR: heptahelical transmembrane G-protein-coupled receptor, AD: autosomal dominant. AR: autosomal recessive.