HH6
MCID: HYP552
MIFTS: 28

Hypogonadotropic Hypogonadism 6 with or Without Anosmia (HH6)

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

Aliases & Classifications for Hypogonadotropic Hypogonadism 6 with or Without Anosmia

MalaCards integrated aliases for Hypogonadotropic Hypogonadism 6 with or Without Anosmia:

Name: Hypogonadotropic Hypogonadism 6 with or Without Anosmia 57 12 72 29 13 6
Kallmann Syndrome 6 72 70
Hh6 57 72
Hypogonadotropic Hypogonadism, Type 6 with/without Anosmia 39
Kal6 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
intrafamilial phenotypic variability


HPO:

31
hypogonadotropic hypogonadism 6 with or without anosmia:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0090086
OMIM® 57 612702
OMIM Phenotypic Series 57 PS147950
MeSH 44 D017436
ICD10 32 E23.0
UMLS 70 C2675188

Summaries for Hypogonadotropic Hypogonadism 6 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. (612702) (Updated 20-May-2021)

MalaCards based summary : Hypogonadotropic Hypogonadism 6 with or Without Anosmia, also known as kallmann syndrome 6, is related to kallmann syndrome 6. An important gene associated with Hypogonadotropic Hypogonadism 6 with or Without Anosmia is FGF8 (Fibroblast Growth Factor 8). Affiliated tissues include pituitary, bone and uterus, and related phenotypes are anosmia and hyposmia

Disease Ontology : 12 A hypogonadotropic hypogonadism that is characterized by autosomal dominant inheritance and has material basis in heterozygous mutation in the FGF8 gene on chromosome 10q24, sometimes in association with mutation in another gene.

UniProtKB/Swiss-Prot : 72 Hypogonadotropic hypogonadism 6 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 6 with or Without Anosmia

Diseases in the Hypogonadotropic Hypogonadism 7 with or Without Anosmia family:

Hypogonadotropic Hypogonadism 2 with or Without Anosmia Hypogonadotropic Hypogonadism 23 Without Anosmia
Hypogonadotropic Hypogonadism 24 Without Anosmia Hypogonadotropic Hypogonadism 3 with or Without Anosmia
Hypogonadotropic Hypogonadism 1 with or Without Anosmia Hypogonadotropic Hypogonadism 4 with or Without Anosmia
Hypogonadotropic Hypogonadism 5 with or Without Anosmia Hypogonadotropic Hypogonadism 6 with or Without Anosmia
Hypogonadotropic Hypogonadism 8 with or Without Anosmia Hypogonadotropic Hypogonadism 9 with or Without Anosmia
Hypogonadotropic Hypogonadism 10 with or Without Anosmia Hypogonadotropic Hypogonadism 11 with or Without Anosmia
Hypogonadotropic Hypogonadism 12 with or Without Anosmia Hypogonadotropic Hypogonadism 13 with or Without Anosmia
Hypogonadotropic Hypogonadism 14 with or Without Anosmia Hypogonadotropic Hypogonadism 15 with or Without Anosmia
Hypogonadotropic Hypogonadism 16 with or Without Anosmia Hypogonadotropic Hypogonadism 17 with or Without Anosmia
Hypogonadotropic Hypogonadism 18 with or Without Anosmia Hypogonadotropic Hypogonadism 19 with or Without Anosmia
Hypogonadotropic Hypogonadism 20 with or Without Anosmia Hypogonadotropic Hypogonadism 21 with or Without Anosmia
Hypogonadotropic Hypogonadism 22 with or Without Anosmia

Diseases related to Hypogonadotropic Hypogonadism 6 with or Without Anosmia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 kallmann syndrome 6 11.5

Symptoms & Phenotypes for Hypogonadotropic Hypogonadism 6 with or Without Anosmia

Human phenotypes related to Hypogonadotropic Hypogonadism 6 with or Without Anosmia:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 anosmia 31 occasional (7.5%) HP:0000458
2 hyposmia 31 occasional (7.5%) HP:0004409
3 high palate 31 HP:0000218
4 delayed skeletal maturation 31 HP:0002750
5 cryptorchidism 31 HP:0000028
6 primary amenorrhea 31 HP:0000786
7 micropenis 31 HP:0000054
8 small pituitary gland 31 HP:0012506
9 cleft lip 31 HP:0410030
10 hypogonadotropic hypogonadism 31 HP:0000044

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Genitourinary Internal Genitalia Female:
primary amenorrhea
small ovaries
prepubertal uterus

Neurologic Central Nervous System:
small pituitary gland
partial empty sella
hypoplastic olfactory bulbs and tracts (in some patients)

Skeletal:
delayed bone age
low bone density

Genitourinary Internal Genitalia Male:
undescended testes
low testicular volume

Chest Breasts:
no breast development

Skeletal Hands:
hyperlaxity of digits

Genitourinary External Genitalia Male:
micropenis
hypogonadism

Head And Neck Mouth:
high-arched palate
cleft lip and palate

Endocrine Features:
delayed or absent puberty
low or undetectable serum estradiol (e2) levels
apulsatile luteinizing hormone (lh) secretion pattern
undetectable lh levels
low or undetectable follicle-stimulating hormone (fsh) levels
more
Head And Neck Nose:
anosmia (in some patients)
hyposmia (in some patients)

Skeletal Limbs:
eunuchoidal proportions

Clinical features from OMIM®:

612702 (Updated 20-May-2021)

Drugs & Therapeutics for Hypogonadotropic Hypogonadism 6 with or Without Anosmia

Search Clinical Trials , NIH Clinical Center for Hypogonadotropic Hypogonadism 6 with or Without Anosmia

Genetic Tests for Hypogonadotropic Hypogonadism 6 with or Without Anosmia

Genetic tests related to Hypogonadotropic Hypogonadism 6 with or Without Anosmia:

# Genetic test Affiliating Genes
1 Hypogonadotropic Hypogonadism 6 with or Without Anosmia 29 FGF8

Anatomical Context for Hypogonadotropic Hypogonadism 6 with or Without Anosmia

MalaCards organs/tissues related to Hypogonadotropic Hypogonadism 6 with or Without Anosmia:

40
Pituitary, Bone, Uterus, Testes, Breast

Publications for Hypogonadotropic Hypogonadism 6 with or Without Anosmia

Articles related to Hypogonadotropic Hypogonadism 6 with or Without Anosmia:

# Title Authors PMID Year
1
Nonsense mutations in FGF8 gene causing different degrees of human gonadotropin-releasing deficiency. 6 57
20463092 2010
2
Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice. 6 57
18596921 2008
3
Prioritizing genetic testing in patients with Kallmann syndrome using clinical phenotypes. 6
23533228 2013
4
Reversal of idiopathic hypogonadotropic hypogonadism. 57
17761590 2007
5
Treatment situation of male hypogonadotropic hypogonadism in pediatrics and proposal of testosterone and gonadotropins replacement therapy protocols. 61
26019400 2015
6
Congenital heart disease associated with sporadic Kallmann syndrome. 61
8322819 1993

Variations for Hypogonadotropic Hypogonadism 6 with or Without Anosmia

ClinVar genetic disease variations for Hypogonadotropic Hypogonadism 6 with or Without Anosmia:

6 (show all 14)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FGF8 NM_033163.4(FGF8):c.77C>T (p.Pro26Leu) SNV Pathogenic 9122 rs137852660 GRCh37: 10:103534966-103534966
GRCh38: 10:101775209-101775209
2 FGF8 NM_001206389.1(FGF8):c.-153C>A SNV Pathogenic 9121 rs137852659 GRCh37: 10:103535526-103535526
GRCh38: 10:101775769-101775769
3 FGF8 NM_006119.5(FGF8):c.70-256T>C SNV Pathogenic 9123 rs137852661 GRCh37: 10:103534925-103534925
GRCh38: 10:101775168-101775168
4 FGF8 NM_001206389.1(FGF8):c.-15A>G SNV Pathogenic 9124 rs137852662 GRCh37: 10:103534528-103534528
GRCh38: 10:101774771-101774771
5 FGF8 NM_033163.4(FGF8):c.379C>T (p.Arg127Ter) SNV Pathogenic 599013 rs137852663 GRCh37: 10:103531285-103531285
GRCh38: 10:101771528-101771528
6 FGF8 NM_033163.4(FGF8):c.385C>T (p.Arg129Ter) SNV Pathogenic 235082 rs876661330 GRCh37: 10:103531279-103531279
GRCh38: 10:101771522-101771522
7 FGF8 NM_006119.5(FGF8):c.292C>G (p.Arg98Gly) SNV Pathogenic 9125 rs137852663 GRCh37: 10:103531285-103531285
GRCh38: 10:101771528-101771528
8 FGF8 NM_001206389.1(FGF8):c.-76C>G SNV Likely pathogenic 140613 rs606231408 GRCh37: 10:103534589-103534589
GRCh38: 10:101774832-101774832
9 FGF8 NM_033163.4(FGF8):c.628_629dup (p.His211fs) Duplication Likely pathogenic 435185 rs1554834303 GRCh37: 10:103530191-103530192
GRCh38: 10:101770434-101770435
10 FGF8 NM_033163.5(FGF8):c.335_337+2del Deletion Uncertain significance 1031556 GRCh37: 10:103534487-103534491
GRCh38: 10:101774730-101774734
11 FGF8 NM_006119.5(FGF8):c.599C>T (p.Thr200Met) SNV Uncertain significance 9126 rs137852664 GRCh37: 10:103530135-103530135
GRCh38: 10:101770378-101770378
12 FGF8 NM_033163.4(FGF8):c.451G>A (p.Gly151Ser) SNV Uncertain significance 140612 rs606231407 GRCh37: 10:103530370-103530370
GRCh38: 10:101770613-101770613
13 FGF8 NM_033163.5(FGF8):c.157-6C>G SNV Uncertain significance 983051 GRCh37: 10:103534675-103534675
GRCh38: 10:101774918-101774918
14 FGF8 NM_033163.4(FGF8):c.445-62G>A SNV Benign 218825 rs3218238 GRCh37: 10:103530438-103530438
GRCh38: 10:101770681-101770681

UniProtKB/Swiss-Prot genetic disease variations for Hypogonadotropic Hypogonadism 6 with or Without Anosmia:

72
# Symbol AA change Variation ID SNP ID
1 FGF8 p.His14Asn VAR_057962 rs137852659
2 FGF8 p.Pro26Leu VAR_057963 rs137852660
3 FGF8 p.Phe40Leu VAR_057964 rs137852661
4 FGF8 p.Lys89Glu VAR_057965 rs137852662
5 FGF8 p.Arg116Gly VAR_057966 rs137852663
6 FGF8 p.Thr218Met VAR_057967 rs137852664

Expression for Hypogonadotropic Hypogonadism 6 with or Without Anosmia

Search GEO for disease gene expression data for Hypogonadotropic Hypogonadism 6 with or Without Anosmia.

Pathways for Hypogonadotropic Hypogonadism 6 with or Without Anosmia

GO Terms for Hypogonadotropic Hypogonadism 6 with or Without Anosmia

Sources for Hypogonadotropic Hypogonadism 6 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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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