Preferred Label : Hypogonadotropic hypogonadism 2 with or without anosmia;
Symbol : HH2;
CISMeF acronym : HH2; KAL2;
Type : Phenotype, molecular basis known;
Alternative titles and symbols : KAL2; Kallmann syndrome 2;
Description : 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).' - Genetic
Heterogeneity of Hypogonadotropic Hypogonadism with or without Anosmia Other forms
of autosomal hypogonadotropic hypogonadism with or without anosmia include HH3 (244200),
caused by mutation in the PROKR2 gene (607123); HH4 (610628), caused by mutation in
the PROK2 gene (607002); HH5 (612370), caused by mutation in the CHD7 gene (608892);
HH6 (612702), caused by mutation in the FGF8 gene (600483); HH7 (146110), caused by
mutation in the GNRHR gene (138850); HH8 (614837), caused by mutation in the KISS1R
gene (604161); HH9 (614838), caused by mutation in the NELF gene (608137); HH10 (614839),
caused by mutation in the TAC3 gene (162330); HH11 (614840), caused by mutation in
the TACR3 gene (162332); HH12 (614841), caused by mutation in the GNRH1 gene (152760);
HH13 (614842), caused by mutation in the KISS1 gene (603286); HH14 (614858), caused
by mutation in the WDR11 gene (606417); HH15 (614880), caused by mutation in the HS6ST1
gene (604846); and HH16 (614897), caused by mutation in the SEMA3A gene (603961).
There is also an X-linked form of the disorder (HH1; 308700), caused by mutation in
the KAL1 gene (300836). There is evidence that mutation in 2 or more of these genes
can work in combination (oligogenicity) to produce GnRH-deficient conditions (summary
by Chan, 2011). Sykiotis et al. (2010), for example, demonstrated that of patients
with an identifiable coding sequence mutation in 1 of 8 genes responsible for isolated
GnRH deficiency, 11% carried mutations in at least one other of these genes as well.
Dode et al. (2006) stated that loss-of-function mutations in the KAL1 (300836) and
FGFR1 genes account for approximately 20% of all cases of Kallmann syndrome and that
mutations in the PROKR2 and PROK2 genes account for an additional 10%.;
Inheritance : Autosomal dominant;
Molecular basis : Caused by mutation in the fibroblast growth factor receptor-1 gene ();
Prefixed ID : #147950;
Origin ID : 147950;
UMLS CUI : C1563720;
Automatic exact mappings (from CISMeF team)
- Broader ORDO disease(s)
- Currated CISMeF NLP mapping
- DO Cross reference
- Genes related to phenotype
- HPO term(s)
- ORDO concept(s)
- Semantic type(s)
- UMLS correspondences (same concept)
- Validated automatic mappings to NTBT
