MCID: HYP531
MIFTS: 23

Hypogonadotropic Hypogonadism 4 with or Without Anosmia

Categories: Genetic diseases, Endocrine diseases

Aliases & Classifications for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

MalaCards integrated aliases for Hypogonadotropic Hypogonadism 4 with or Without Anosmia:

Name: Hypogonadotropic Hypogonadism 4 with or Without Anosmia 57 12 75 13
Kallmann Syndrome 4 75 73
Hh4 57 75
Hypogonadotropic Hypogonadism, Type 4 with/without Anosmia 40
Kal4 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
incomplete penetrance
phenotype may be oligogenic in some patients who carry mutations in more than one hh-associated gene


HPO:

32
hypogonadotropic hypogonadism 4 with or without anosmia:
Onset and clinical course incomplete penetrance
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

OMIM : 57 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. (610628)

MalaCards based summary : Hypogonadotropic Hypogonadism 4 with or Without Anosmia, also known as kallmann syndrome 4, is related to kallmann syndrome 4. An important gene associated with Hypogonadotropic Hypogonadism 4 with or Without Anosmia is PROK2 (Prokineticin 2). Affiliated tissues include pituitary, olfactory bulb and testes, and related phenotypes are cryptorchidism and hypogonadotrophic hypogonadism

Disease Ontology : 12 A hypogonadotropic hypogonadism that has material basis in heterozygous mutation in the prokineticin-2 gene (PROK2) on chromosome 3p13, sometimes in association with mutation in another gene.

UniProtKB/Swiss-Prot : 75 Hypogonadotropic hypogonadism 4 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 4 with or Without Anosmia

Diseases related to Hypogonadotropic Hypogonadism 4 with or Without Anosmia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 kallmann syndrome 4 10.9

Symptoms & Phenotypes for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

Symptoms via clinical synopsis from OMIM:

57
Genitourinary External Genitalia Male:
cryptorchidism
micropenis
small testes

Endocrine Features:
hypogonadotropic hypogonadism
delayed or absent puberty
low to undetectable gonadotropin levels
low testosterone level
low estradiol level
more
Chest Breasts:
delayed or absent thelarche

Skeletal:
osteoporosis (in some patients)

Genitourinary Internal Genitalia Female:
primary amenorrhea

Neurologic Central Nervous System:
seizures (rare)
sleep disorder (rare)
synkinesia (rare)

Head And Neck Nose:
hyposmia/anosmia (in some patients)

Growth Weight:
obesity (rare)


Clinical features from OMIM:

610628

Human phenotypes related to Hypogonadotropic Hypogonadism 4 with or Without Anosmia:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 cryptorchidism 32 HP:0000028
2 hypogonadotrophic hypogonadism 32 HP:0000044
3 micropenis 32 HP:0000054
4 anosmia 32 occasional (7.5%) HP:0000458
5 primary amenorrhea 32 HP:0000786
6 diabetes mellitus 32 occasional (7.5%) HP:0000819
7 osteoporosis 32 occasional (7.5%) HP:0000939
8 seizures 32 occasional (7.5%) HP:0001250
9 obesity 32 occasional (7.5%) HP:0001513
10 decreased testicular size 32 HP:0008734

Drugs & Therapeutics for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Heart Health 4 Moms Completed NCT02147626 Not Applicable

Search NIH Clinical Center for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

Genetic Tests for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

Anatomical Context for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

MalaCards organs/tissues related to Hypogonadotropic Hypogonadism 4 with or Without Anosmia:

41
Pituitary, Olfactory Bulb, Testes, Heart

Publications for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

Variations for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

UniProtKB/Swiss-Prot genetic disease variations for Hypogonadotropic Hypogonadism 4 with or Without Anosmia:

75
# Symbol AA change Variation ID SNP ID
1 PROK2 p.Gly32Arg VAR_030955 rs104893767
2 PROK2 p.Arg73Cys VAR_030956 rs121434272
3 PROK2 p.Ala24Pro VAR_069970 rs587777863
4 PROK2 p.Cys34Tyr VAR_072177 rs587777864
5 PROK2 p.Ile50Met VAR_072178
6 PROK2 p.Cys46Tyr VAR_072991

ClinVar genetic disease variations for Hypogonadotropic Hypogonadism 4 with or Without Anosmia:

6
(show all 11)
# Gene Variation Type Significance SNP ID Assembly Location
1 PROK2 NM_001126128.1(PROK2): c.94G> C (p.Gly32Arg) single nucleotide variant Pathogenic rs104893767 GRCh37 Chromosome 3, 71834110: 71834110
2 PROK2 NM_001126128.1(PROK2): c.94G> C (p.Gly32Arg) single nucleotide variant Pathogenic rs104893767 GRCh38 Chromosome 3, 71784959: 71784959
3 PROK2 PROK2, 1-BP INS, 234T insertion Pathogenic
4 PROK2 NM_001126128.1(PROK2): c.163delA (p.Ile55Terfs) deletion Pathogenic rs554675432 GRCh38 Chromosome 3, 71781526: 71781526
5 PROK2 NM_001126128.1(PROK2): c.163delA (p.Ile55Terfs) deletion Pathogenic rs554675432 GRCh37 Chromosome 3, 71830677: 71830677
6 PROK2 NM_021935.3(PROK2): c.217C> T (p.Arg73Cys) single nucleotide variant Pathogenic rs121434272 GRCh37 Chromosome 3, 71830623: 71830623
7 PROK2 NM_021935.3(PROK2): c.217C> T (p.Arg73Cys) single nucleotide variant Pathogenic rs121434272 GRCh38 Chromosome 3, 71781472: 71781472
8 PROK2 NM_001126128.1(PROK2): c.70G> C (p.Ala24Pro) single nucleotide variant Pathogenic rs587777863 GRCh38 Chromosome 3, 71784983: 71784983
9 PROK2 NM_001126128.1(PROK2): c.70G> C (p.Ala24Pro) single nucleotide variant Pathogenic rs587777863 GRCh37 Chromosome 3, 71834134: 71834134
10 PROK2 NM_001126128.1(PROK2): c.101G> A (p.Cys34Tyr) single nucleotide variant Pathogenic rs587777864 GRCh38 Chromosome 3, 71781588: 71781588
11 PROK2 NM_001126128.1(PROK2): c.101G> A (p.Cys34Tyr) single nucleotide variant Pathogenic rs587777864 GRCh37 Chromosome 3, 71830739: 71830739

Expression for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

Search GEO for disease gene expression data for Hypogonadotropic Hypogonadism 4 with or Without Anosmia.

Pathways for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

GO Terms for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

Sources for Hypogonadotropic Hypogonadism 4 with or Without Anosmia

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