Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary ... Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; 152760) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by Raivio et al., 2007). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).' For a discussion of genetic heterogeneity of hypogonadotropic hypogonadism with or without anosmia, see 147950.
In an 18-year-old Romanian man from a Transylvanian mountain village who had normosmic hypogonadotropic hypogonadism and was negative for mutation in the GNRHR1, GPR54, KISS1, FGFR1, and GNRH2 genes, Bouligand et al. (2009) identified homozygosity for a 1-bp ... In an 18-year-old Romanian man from a Transylvanian mountain village who had normosmic hypogonadotropic hypogonadism and was negative for mutation in the GNRHR1, GPR54, KISS1, FGFR1, and GNRH2 genes, Bouligand et al. (2009) identified homozygosity for a 1-bp insertion in the GNRH1 gene (152760.0001). His affected sister was also homozygous for the mutation, and his unaffected parents and an unaffected sister were heterozygotes, as was 1 of 200 ancestrally matched Romanian controls; haplotype analysis suggested a founding event 8 to 50 generations earlier. The mutation was not found in 100 unrelated Caucasian eugonadal individuals or in 145 unrelated Caucasian patients with sporadic normosmic IHH.