HH21
MCID: HYP817
MIFTS: 26

Hypogonadotropic Hypogonadism 21 with or Without Anosmia (HH21)

Categories: Cardiovascular diseases, Ear diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Hypogonadotropic Hypogonadism 21 with or Without Anosmia

MalaCards integrated aliases for Hypogonadotropic Hypogonadism 21 with or Without Anosmia:

Name: Hypogonadotropic Hypogonadism 21 with or Without Anosmia 57 12 72 29 6 70
Hh21 57 72
Hypogonadotropic Hypogonadism 21 with Anosmia, Susceptibility to 6
Hypogonadism, Hypogonadotropic, Type 21 with/without Anosmia 39
Hypogonadotropic Hypogonadism 21 with Anosmia 57

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant (see miscellaneous below)

Miscellaneous:
phenotypic variability within families and among patients carrying the same mutation appears to be due to the oligogenic nature of the disorder, with some patients having mutations in more than 1 neuroendocrine-related gene


HPO:

31
hypogonadotropic hypogonadism 21 with or without anosmia:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0090093
OMIM® 57 615271
OMIM Phenotypic Series 57 PS147950
MeSH 44 D007006
ICD10 32 E23.0
UMLS 70 C3808986

Summaries for Hypogonadotropic Hypogonadism 21 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 hypogonadotropic hypogonadism with or without anosmia as well as a discussion of oligogenicity of this disorder, see 147950. (615271) (Updated 05-Apr-2021)

MalaCards based summary : Hypogonadotropic Hypogonadism 21 with or Without Anosmia, is also known as hh21. An important gene associated with Hypogonadotropic Hypogonadism 21 with or Without Anosmia is FLRT3 (Fibronectin Leucine Rich Transmembrane Protein 3). Affiliated tissues include pituitary and heart, and related phenotypes are osteopenia and hearing impairment

Disease Ontology : 12 A hypogonadotropic hypogonadism that has material basis in heterozygous mutation in the FLRT3 gene on 20p11, sometimes in association with mutations in other genes.

UniProtKB/Swiss-Prot : 72 Hypogonadotropic hypogonadism 21 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 21 with or Without Anosmia

Symptoms & Phenotypes for Hypogonadotropic Hypogonadism 21 with or Without Anosmia

Human phenotypes related to Hypogonadotropic Hypogonadism 21 with or Without Anosmia:

31
# Description HPO Frequency HPO Source Accession
1 osteopenia 31 occasional (7.5%) HP:0000938
2 hearing impairment 31 occasional (7.5%) HP:0000365
3 osteoporosis 31 occasional (7.5%) HP:0000939

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal:
osteopenia (in some patients)
osteoporosis (in some patients)
fractures (in some patients)

Endocrine Features:
delayed or absent puberty

Neurologic Central Nervous System:
hyposmia/anosmia (in some patients)

Head And Neck Mouth:
cleft lip and/or palate (in some patients)

Genitourinary:
delayed or absent puberty

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

Head And Neck Ears:
hearing loss (in some patients)

Clinical features from OMIM®:

615271 (Updated 05-Apr-2021)

Drugs & Therapeutics for Hypogonadotropic Hypogonadism 21 with or Without Anosmia

Search Clinical Trials , NIH Clinical Center for Hypogonadotropic Hypogonadism 21 with or Without Anosmia

Genetic Tests for Hypogonadotropic Hypogonadism 21 with or Without Anosmia

Genetic tests related to Hypogonadotropic Hypogonadism 21 with or Without Anosmia:

# Genetic test Affiliating Genes
1 Hypogonadotropic Hypogonadism 21 with or Without Anosmia 29 FLRT3

Anatomical Context for Hypogonadotropic Hypogonadism 21 with or Without Anosmia

MalaCards organs/tissues related to Hypogonadotropic Hypogonadism 21 with or Without Anosmia:

40
Pituitary, Heart

Publications for Hypogonadotropic Hypogonadism 21 with or Without Anosmia

Articles related to Hypogonadotropic Hypogonadism 21 with or Without Anosmia:

(show all 16)
# Title Authors PMID Year
1
Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. 57 6
23643382 2013
2
Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism. 6 57
21700882 2011
3
The syndrome of anosmia with hypogonadotropic hypogonadism: a genetic study of 18 new families and a review. 57 6
6881209 1983
4
Reversal of idiopathic hypogonadotropic hypogonadism. 57
17761590 2007
5
Effect of left atrial ligation-driven altered inflow hemodynamics on embryonic heart development: clues for prenatal progression of hypoplastic left heart syndrome. 61
33481120 2021
6
Fluid mechanics of the left atrial ligation chick embryonic model of hypoplastic left heart syndrome. 61
33774755 2021
7
Chicken Second Branchial Arch Progenitor Cells Contribute to Heart Musculature in vitro and in vivo. 61
33423027 2021
8
Altered haemodynamics causes aberrations in the epicardium. 61
30882904 2019
9
Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart. 61
28576718 2017
10
Neurovascular anatomy of the embryonic quail hindlimb. 61
19685501 2009
11
Arterial hemodynamics and mechanical properties after circulatory intervention in the chick embryo. 61
15879068 2005
12
Cloning and expression pattern of connexin39, a new member of the gap junction gene family isolated from the neural tube of chicken embryos. 61
15019991 2004
13
Pressure overload alters stress-strain properties of the developing chick heart. 61
12855423 2003
14
The pattern of neurovascular development in the forelimb of the quail embryo. 61
12221008 2002
15
The avian griseum tectale: cytoarchitecture, NOS expression and neurogenesis. 61
11922988 2002
16
Cloning of a pleiotropic gene that positively controls biosynthesis of A-factor, actinorhodin, and prodigiosin in Streptomyces coelicolor A3(2) and Streptomyces lividans. 61
6309746 1983

Variations for Hypogonadotropic Hypogonadism 21 with or Without Anosmia

ClinVar genetic disease variations for Hypogonadotropic Hypogonadism 21 with or Without Anosmia:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FLRT3 , MACROD2 NM_198391.3(FLRT3):c.1016A>G (p.Lys339Arg) SNV Pathogenic 50865 rs398124654 GRCh37: 20:14307137-14307137
GRCh38: 20:14326491-14326491
2 FLRT3 , MACROD2 NM_198391.3(FLRT3):c.290A>G (p.Glu97Gly) SNV risk factor 50862 rs398124651 GRCh37: 20:14307863-14307863
GRCh38: 20:14327217-14327217
3 FLRT3 , MACROD2 NM_198391.3(FLRT3):c.431G>T (p.Ser144Ile) SNV risk factor 50863 rs398124652 GRCh37: 20:14307722-14307722
GRCh38: 20:14327076-14327076
4 FLRT3 , MACROD2 NM_198391.3(FLRT3):c.205C>A (p.Gln69Lys) SNV risk factor 50864 rs398124653 GRCh37: 20:14307948-14307948
GRCh38: 20:14327302-14327302
5 FLRT3 , MACROD2 NM_198391.3(FLRT3):c.1255A>T (p.Thr419Ser) SNV Uncertain significance 1029224 GRCh37: 20:14306898-14306898
GRCh38: 20:14326252-14326252

UniProtKB/Swiss-Prot genetic disease variations for Hypogonadotropic Hypogonadism 21 with or Without Anosmia:

72
# Symbol AA change Variation ID SNP ID
1 FLRT3 p.Gln69Lys VAR_069950 rs398124653
2 FLRT3 p.Glu97Gly VAR_069951 rs398124651
3 FLRT3 p.Ser144Ile VAR_069952 rs398124652
4 FLRT3 p.Lys339Arg VAR_069953 rs398124654

Expression for Hypogonadotropic Hypogonadism 21 with or Without Anosmia

Search GEO for disease gene expression data for Hypogonadotropic Hypogonadism 21 with or Without Anosmia.

Pathways for Hypogonadotropic Hypogonadism 21 with or Without Anosmia

GO Terms for Hypogonadotropic Hypogonadism 21 with or Without Anosmia

Sources for Hypogonadotropic Hypogonadism 21 with or Without Anosmia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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