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 autosomal hypogonadotropic hypogonadism with or without anosmia, see 147950.
Dode et al. (2006) noted that Kallmann syndrome patients with mutations in PROKR2 or PROK2 had variable degrees of olfactory and reproductive dysfunction and did not seem to have any of the occasional clinical anomalies that had been ... Dode et al. (2006) noted that Kallmann syndrome patients with mutations in PROKR2 or PROK2 had variable degrees of olfactory and reproductive dysfunction and did not seem to have any of the occasional clinical anomalies that had been reported in previously characterized genetic forms of the disease, i.e., bimanual synkinesis, renal agenesis, dental agenesis, and cleft lip or palate.
In a study of 192 patients with Kallmann syndrome, Dode et al. (2006) identified 10 and 4 different point mutations in the PROKR2 gene (e.g., 607123.0001-607123.0005) and in one of its ligands, prokineticin-2 (PROK2; 607002), respectively. One of ... In a study of 192 patients with Kallmann syndrome, Dode et al. (2006) identified 10 and 4 different point mutations in the PROKR2 gene (e.g., 607123.0001-607123.0005) and in one of its ligands, prokineticin-2 (PROK2; 607002), respectively. One of the patients was heterozygous for a PROKR2 mutation (607123.0001) and a missense mutation in KAL1 (300836.0012), indicating possible digenic inheritance of the disorder.