HH8
MCID: HYP514
MIFTS: 27

Hypogonadotropic Hypogonadism 8 with or Without Anosmia (HH8)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Reproductive diseases, Smell/Taste diseases

Aliases & Classifications for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

MalaCards integrated aliases for Hypogonadotropic Hypogonadism 8 with or Without Anosmia:

Name: Hypogonadotropic Hypogonadism 8 with or Without Anosmia 56 12 73 29 13 6
Hh8 56 73
Hypogonadism, Hypogonadotropic, Type 8 with/without Anosmia 39
Hypogonadotropic Hypogonadism 8 Without Anosmia 6

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
variable expressivity within a family


HPO:

31
hypogonadotropic hypogonadism 8 with or without anosmia:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

OMIM : 56 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 as well as a discussion of oligogenicity of this disorder, see 147950. (614837)

MalaCards based summary : Hypogonadotropic Hypogonadism 8 with or Without Anosmia, is also known as hh8. An important gene associated with Hypogonadotropic Hypogonadism 8 with or Without Anosmia is KISS1R (KISS1 Receptor). Affiliated tissues include pituitary, olfactory bulb and uterus, and related phenotypes are anosmia and delayed skeletal maturation

Disease Ontology : 12 A hypogonadotropic hypogonadism that has material basis in homozygous or compound heterozygous mutation in the KISS1R gene on chromosome 19p13, sometimes in association with mutation in other genes.

UniProtKB/Swiss-Prot : 73 Hypogonadotropic hypogonadism 8 with or without anosmia: 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. In some cases, it is associated with non- reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin- releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).

Related Diseases for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

Symptoms & Phenotypes for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

Human phenotypes related to Hypogonadotropic Hypogonadism 8 with or Without Anosmia:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 anosmia 31 occasional (7.5%) HP:0000458
2 delayed skeletal maturation 31 HP:0002750
3 cryptorchidism 31 HP:0000028
4 osteopenia 31 HP:0000938
5 primary amenorrhea 31 HP:0000786
6 micropenis 31 HP:0000054
7 azoospermia 31 HP:0000027
8 gynecomastia 31 HP:0000771
9 decreased testicular size 31 HP:0008734
10 hypoplasia of the uterus 31 HP:0000013
11 gonadotropin deficiency 31 HP:0008213
12 hypogonadotropic hypogonadism 31 HP:0000044

Symptoms via clinical synopsis from OMIM:

56
Genitourinary External Genitalia Male:
cryptorchidism
micropenis
azoospermia
small testes

Genitourinary Internal Genitalia Female:
primary amenorrhea
hypoplastic uterus
small ovaries (in some patients)
reduced number of follicles seen on ultrasound

Endocrine Features:
delayed or absent puberty
eunuchoid appearance of males
partial or complete serum gonadotropin deficiency
low estradiol in females
low testosterone in males

Skeletal:
osteopenia
delayed bone age

Chest Breasts:
delayed or absent thelarche
gynecomastia (in untreated males)

Skin Nails Hair Hair:
near-normal pubic hair

Clinical features from OMIM:

614837

Drugs & Therapeutics for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

Search Clinical Trials , NIH Clinical Center for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

Genetic Tests for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

Genetic tests related to Hypogonadotropic Hypogonadism 8 with or Without Anosmia:

# Genetic test Affiliating Genes
1 Hypogonadotropic Hypogonadism 8 with or Without Anosmia 29 KISS1R

Anatomical Context for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

MalaCards organs/tissues related to Hypogonadotropic Hypogonadism 8 with or Without Anosmia:

40
Pituitary, Olfactory Bulb, Uterus, Bone, Ovary, Testes

Publications for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

Articles related to Hypogonadotropic Hypogonadism 8 with or Without Anosmia:

# Title Authors PMID Year
1
Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. 6 56
23643382 2013
2
Two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in KISS1R (KISS1 receptor): clinical evaluation and molecular characterization of a novel mutation. 56 6
23349759 2013
3
Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54. 6 56
17164310 2007
4
The GPR54 gene as a regulator of puberty. 6 56
14573733 2003
5
Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. 6 56
12944565 2003
6
Autosomal recessive idiopathic hypogonadotropic hypogonadism: genetic analysis excludes mutations in the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes. 56 6
12788881 2003
7
Disease-causing mutation in GPR54 reveals the importance of the second intracellular loop for class A G-protein-coupled receptor function. 6
18772143 2008
8
Reversal of idiopathic hypogonadotropic hypogonadism. 56
17761590 2007
9
Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency 6
20301509 2007
10
A locus for autosomal recessive idiopathic hypogonadotropic hypogonadism on chromosome 19p13.3. 56
12788910 2003

Variations for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

ClinVar genetic disease variations for Hypogonadotropic Hypogonadism 8 with or Without Anosmia:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KISS1R NM_032551.5(KISS1R):c.443T>C (p.Leu148Ser)SNV Pathogenic 5755 rs28939719 19:919563-919563 19:919563-919563
2 KISS1R NM_032551.5(KISS1R):c.991C>T (p.Arg331Ter)SNV Pathogenic 5756 rs104894701 19:920542-920542 19:920542-920542
3 KISS1R NM_032551.5(KISS1R):c.1195T>A (p.Ter399Arg)SNV Pathogenic 5757 rs104894702 19:920746-920746 19:920746-920746
4 KISS1R KISS1R, 155-BP DELdeletion Pathogenic 5758
5 KISS1R NM_032551.5(KISS1R):c.305T>C (p.Leu102Pro)SNV Pathogenic 5759 rs104894703 19:918604-918604 19:918604-918604
6 KISS1R NM_032551.5(KISS1R):c.937T>C (p.Tyr313His)SNV Pathogenic 156474 rs587777844 19:920488-920488 19:920488-920488
7 KISS1R NM_032551.5(KISS1R):c.581C>A (p.Ala194Asp)SNV risk factor 50861 rs397514699 19:919949-919949 19:919949-919949

UniProtKB/Swiss-Prot genetic disease variations for Hypogonadotropic Hypogonadism 8 with or Without Anosmia:

73
# Symbol AA change Variation ID SNP ID
1 KISS1R p.Leu148Ser VAR_021392 rs28939719
2 KISS1R p.Cys223Arg VAR_021393
3 KISS1R p.Arg297Leu VAR_021394 rs144670595
4 KISS1R p.Leu102Pro VAR_043906 rs104894703
5 KISS1R p.Ala189Thr VAR_069961 rs73507527
6 KISS1R p.Ala194Asp VAR_069962 rs397514699
7 KISS1R p.Ser262Leu VAR_072975 rs745580229

Expression for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

Search GEO for disease gene expression data for Hypogonadotropic Hypogonadism 8 with or Without Anosmia.

Pathways for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

GO Terms for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

Sources for Hypogonadotropic Hypogonadism 8 with or Without Anosmia

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