MCID: HYP565
MIFTS: 24

Hypogonadotropic Hypogonadism 3 with or Without Anosmia

Categories: Genetic diseases, Endocrine diseases

Aliases & Classifications for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

MalaCards integrated aliases for Hypogonadotropic Hypogonadism 3 with or Without Anosmia:

Name: Hypogonadotropic Hypogonadism 3 with or Without Anosmia 57 12 75 13
Hh3 57 75
Hypogonadotropic Hypogonadism, Type 3 with/without Anosmia 40
Hypogonadotropic Hypogonadism 3 Without Anosmia 6
Kallmann Syndrome, Type 3, Recessive 73
Kallmann Syndrome 3 75
Kal3 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
incomplete penetrance
some patients experience later reversal of hypogonadotropic hypogonadism
phenotype may be oligogenic in some patients who carry mutations in more than one hh-associated gene


HPO:

32
hypogonadotropic hypogonadism 3 with or without anosmia:
Onset and clinical course incomplete penetrance
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Hypogonadotropic Hypogonadism 3 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. (244200)

MalaCards based summary : Hypogonadotropic Hypogonadism 3 with or Without Anosmia, also known as hh3, is related to kallmann syndrome 3. An important gene associated with Hypogonadotropic Hypogonadism 3 with or Without Anosmia is PROKR2 (Prokineticin Receptor 2). Affiliated tissues include pituitary and olfactory bulb, and related phenotypes are pectus excavatum and seizures

UniProtKB/Swiss-Prot : 75 Hypogonadotropic hypogonadism 3 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).

Disease Ontology : 12 A hypogonadotropic hypogonadism that has material basis in heterozygous mutation in the PROKR2 gene on chromosome 20p12, sometimes in association with mutation in another gene.

Related Diseases for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

Diseases related to Hypogonadotropic Hypogonadism 3 with or Without Anosmia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 kallmann syndrome 3 10.9

Symptoms & Phenotypes for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

Symptoms via clinical synopsis from OMIM:

57
Chest External Features:
pectus excavatum

Genitourinary External Genitalia Male:
cryptorchidism
micropenis

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

Chest Breasts:
delayed or absent thelarche

Head And Neck Ears:
hearing loss (rare)

Muscle Soft Tissue:
fibrous dysplasia (rare)

Skeletal Feet:
pes planus

Genitourinary Internal Genitalia Female:
primary amenorrhea

Neurologic Central Nervous System:
seizures (rare)
synkinesia

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

Skeletal Hands:
hyperlaxity of digits (rare)


Clinical features from OMIM:

244200

Human phenotypes related to Hypogonadotropic Hypogonadism 3 with or Without Anosmia:

32 (show all 13)
# Description HPO Frequency HPO Source Accession
1 pectus excavatum 32 HP:0000767
2 seizures 32 occasional (7.5%) HP:0001250
3 hearing impairment 32 occasional (7.5%) HP:0000365
4 pes planus 32 HP:0001763
5 cleft palate 32 HP:0000175
6 cryptorchidism 32 HP:0000028
7 primary amenorrhea 32 HP:0000786
8 hypogonadotrophic hypogonadism 32 HP:0000044
9 hypotelorism 32 HP:0000601
10 cleft upper lip 32 HP:0000204
11 anosmia 32 HP:0000458
12 micropenis 32 HP:0000054
13 unilateral renal agenesis 32 HP:0000122

Drugs & Therapeutics for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 WEE1 Inhibitor AZD1775 and Local Radiation Therapy in Treating Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas Recruiting NCT01922076 Phase 1 Adavosertib

Search NIH Clinical Center for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

Genetic Tests for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

Anatomical Context for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

MalaCards organs/tissues related to Hypogonadotropic Hypogonadism 3 with or Without Anosmia:

41
Pituitary, Olfactory Bulb

Publications for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

Variations for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

UniProtKB/Swiss-Prot genetic disease variations for Hypogonadotropic Hypogonadism 3 with or Without Anosmia:

75 (show all 16)
# Symbol AA change Variation ID SNP ID
1 PROKR2 p.Arg85Cys VAR_030957 rs141090506
2 PROKR2 p.Arg85His VAR_030958 rs74315418
3 PROKR2 p.Arg164Gln VAR_030959 rs751875578
4 PROKR2 p.Leu173Arg VAR_030960 rs74315416
5 PROKR2 p.Trp178Ser VAR_030961 rs201835496
6 PROKR2 p.Gln210Arg VAR_030962 rs74315417
7 PROKR2 p.Pro290Ser VAR_030964 rs149992595
8 PROKR2 p.Met323Ile VAR_030965 rs74315419
9 PROKR2 p.Val115Met VAR_069964 rs138672528
10 PROKR2 p.Ser202Gly VAR_069965 rs200755554
11 PROKR2 p.Tyr113His VAR_072173 rs202203360
12 PROKR2 p.Ser188Leu VAR_072174 rs376239580
13 PROKR2 p.Arg248Gln VAR_072175 rs376142095
14 PROKR2 p.Arg357Trp VAR_072176 rs375036628
15 PROKR2 p.Val158Ile VAR_072978 rs368732206
16 PROKR2 p.Val334Met VAR_072979 rs371564610

ClinVar genetic disease variations for Hypogonadotropic Hypogonadism 3 with or Without Anosmia:

6
(show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 PROKR2 NM_144773.3(PROKR2): c.629A> G (p.Gln210Arg) single nucleotide variant Pathogenic rs74315417 GRCh37 Chromosome 20, 5283212: 5283212
2 PROKR2 NM_144773.3(PROKR2): c.629A> G (p.Gln210Arg) single nucleotide variant Pathogenic rs74315417 GRCh38 Chromosome 20, 5302566: 5302566
3 PROKR2 NM_144773.3(PROKR2): c.58delC (p.His20Metfs) deletion Pathogenic/Likely pathogenic rs587777834 GRCh38 Chromosome 20, 5314312: 5314312
4 PROKR2 NM_144773.3(PROKR2): c.58delC (p.His20Metfs) deletion Pathogenic/Likely pathogenic rs587777834 GRCh37 Chromosome 20, 5294958: 5294958
5 PROKR2 NM_144773.3(PROKR2): c.969G> A (p.Met323Ile) single nucleotide variant Pathogenic rs74315419 GRCh37 Chromosome 20, 5282872: 5282872
6 PROKR2 NM_144773.3(PROKR2): c.969G> A (p.Met323Ile) single nucleotide variant Pathogenic rs74315419 GRCh38 Chromosome 20, 5302226: 5302226
7 PROKR2 NM_144773.3(PROKR2): c.253C> T (p.Arg85Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs141090506 GRCh37 Chromosome 20, 5294763: 5294763
8 PROKR2 NM_144773.3(PROKR2): c.253C> T (p.Arg85Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs141090506 GRCh38 Chromosome 20, 5314117: 5314117
9 PROKR2 NM_144773.3(PROKR2): c.343G> A (p.Val115Met) single nucleotide variant Pathogenic rs138672528 GRCh37 Chromosome 20, 5294673: 5294673
10 PROKR2 NM_144773.3(PROKR2): c.343G> A (p.Val115Met) single nucleotide variant Pathogenic rs138672528 GRCh38 Chromosome 20, 5314027: 5314027
11 PROKR2 NM_144773.3(PROKR2): c.533G> C (p.Trp178Ser) single nucleotide variant Likely pathogenic rs201835496 GRCh37 Chromosome 20, 5283308: 5283308
12 PROKR2 NM_144773.3(PROKR2): c.533G> C (p.Trp178Ser) single nucleotide variant Likely pathogenic rs201835496 GRCh38 Chromosome 20, 5302662: 5302662
13 PROKR2 NM_144773.3(PROKR2): c.743G> A (p.Arg248Gln) single nucleotide variant Pathogenic rs376142095 GRCh37 Chromosome 20, 5283098: 5283098
14 PROKR2 NM_144773.3(PROKR2): c.743G> A (p.Arg248Gln) single nucleotide variant Pathogenic rs376142095 GRCh38 Chromosome 20, 5302452: 5302452
15 PROKR2 NM_144773.3(PROKR2): c.97T> C (p.Tyr33His) single nucleotide variant Likely pathogenic rs886037916 GRCh38 Chromosome 20, 5314273: 5314273
16 PROKR2 NM_144773.3(PROKR2): c.97T> C (p.Tyr33His) single nucleotide variant Likely pathogenic rs886037916 GRCh37 Chromosome 20, 5294919: 5294919
17 PROKR2 NM_144773.3(PROKR2): c.585G> C (p.Thr195=) single nucleotide variant Benign rs3746682 GRCh37 Chromosome 20, 5283256: 5283256
18 PROKR2 NM_144773.3(PROKR2): c.585G> C (p.Thr195=) single nucleotide variant Benign rs3746682 GRCh38 Chromosome 20, 5302610: 5302610
19 PROKR2 NM_144773.3(PROKR2): c.465C> T (p.Leu155=) single nucleotide variant Benign rs3746684 GRCh37 Chromosome 20, 5283376: 5283376
20 PROKR2 NM_144773.3(PROKR2): c.465C> T (p.Leu155=) single nucleotide variant Benign rs3746684 GRCh38 Chromosome 20, 5302730: 5302730

Expression for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

Search GEO for disease gene expression data for Hypogonadotropic Hypogonadism 3 with or Without Anosmia.

Pathways for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

GO Terms for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

Sources for Hypogonadotropic Hypogonadism 3 with or Without Anosmia

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