[How to explore ... congenital isolated hypogonadotrophic hypogonadism]

Abstract

Congenital Isolated hypogonadotropic hypogonadism (CIHH) is caused by an inherited mechanism of impairment of the pituitary-gonadal axis, interfering with gonads' control. Currently, different forms of HHCI with (Kallmann syndrome or KS) or without anosmia-hyposmia are known. There are six forms of KS already described but in several cases no genetic mutation is found. The genetic anomalies already described are: KAL1 (locus Xp23) coding for anosmine-1, KAL-2 or FGFRI (8p11. locus 2 - p11.1) coding for Fibroblast Growth Factor Receptor 1 (FGFR1), KAL4 or PROk2 (locus 3p21.1) and KAL3 or ProKR2 (locus 20p13) coding respectively for the Prokinecitin-2 and its receptor, KAL5 or CHD7 (locus_8q12.1) coding for a chromodomain helicase DNA-binding protein-7 gene (CHD7) and lastly KAL6 or FGF8 (10Q 24 loci) coding for Fibroblast Growth Factor 8. The other genetic anomalies without anosmia are less frequent. These are associated either with Gnrhl gene (8p2-11. 2), GnRHR (4q21.2), GPR54 (19p13),TAC3R or neurokinine receptor 3 (4 q 25), LH (19q13.32) or FSH (11p13). The isolated congenital hypogonadotrophic hypogonadism phenotype is variable depending on gender, the importance of the deficit, and ultimately, according to a specific regulatory mechanism of the axis, affected by an inherited genetic anomaly. In this review, we describe the essential aspects of the different phenotypes and genotypes of HHCI, in order to assess clinicians an early disease's diagnosis and management.