MCID: HYP513
MIFTS: 40

Hypogonadotropic Hypogonadism 1 with or Without Anosmia

Categories: Genetic diseases, Rare diseases, Smell/Taste diseases, Endocrine diseases

Aliases & Classifications for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

MalaCards integrated aliases for Hypogonadotropic Hypogonadism 1 with or Without Anosmia:

Name: Hypogonadotropic Hypogonadism 1 with or Without Anosmia 53 12 71 13
Kallmann Syndrome 1 53 49 71 28 69
Dysplasia Olfactogenitalis of De Morsier 53 12 71
Kal1 53 49 71
Hypogonadotropic Hypogonadism and Anosmia 53 71
Anosmic Hypogonadism 53 71
Kms 53 71
Hh1 53 71
Hha 53 71
Hypogonadotropic Hypogonadism and Anosmia; Hha 53
Kallmann Syndrome, Type 1, X-Linked 49
Kallmann Syndrome, X-Linked 49
Kallmann Syndrome 1; Kal1 53
Kallmann Syndrome 69

Characteristics:

OMIM:

53
Inheritance:
x-linked recessive

Miscellaneous:
heterozygous females may be susceptible to functional hypothalamic amenorrhea


HPO:

31
hypogonadotropic hypogonadism 1 with or without anosmia:
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

OMIM : 53 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.' For information on the autosomal forms of hypogonadotropic hypogonadism with or without anosmia, see 147950. (308700)

MalaCards based summary : Hypogonadotropic Hypogonadism 1 with or Without Anosmia, also known as kallmann syndrome 1, is related to kabuki syndrome 1 and hemangioma-thrombocytopenia syndrome, and has symptoms including ataxia, anosmia and high palate. An important gene associated with Hypogonadotropic Hypogonadism 1 with or Without Anosmia is ANOS1 (Anosmin 1). The drugs rituximab and Antibodies have been mentioned in the context of this disorder. Affiliated tissues include pituitary, olfactory bulb and kidney.

Disease Ontology : 12 A hypogonadotropic hypogonadism that has material basis in mutation in the KAL1 gene on chromosome Xp22.3, sometimes in association with mutation in another gene.

NIH Rare Diseases : 49 Kallmann syndrome 1 is an inherited disorder characterized by delayed or absent puberty and an impaired sense of smell. Other symptoms may include color blindness, cleft lip or palate, abnormal eye movements, hearing loss, failure of one of the kidneys to develop, mirror image hand movements, abnormalities of tooth development, and infertility. This disorder is a form of hypogonadotropic hypogonadism. Affected males are usually born with a small penis and undescended testicles. Affected females usually do not begin menstruating at puberty and have little or no breast development. Kallmann syndrome 1 is the most common type of Kallmann syndrome (there are four types identified at this time). It is caused by mutations in the KAL1 gene and is inherited in an X-linked recessive fashion.   Last updated: 12/22/2011

UniProtKB/Swiss-Prot : 71 Hypogonadotropic hypogonadism 1 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 1 with or Without Anosmia

Graphical network of the top 20 diseases related to Hypogonadotropic Hypogonadism 1 with or Without Anosmia:



Diseases related to Hypogonadotropic Hypogonadism 1 with or Without Anosmia

Symptoms & Phenotypes for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

Symptoms via clinical synopsis from OMIM:

53
Genitourinary Internal Genitalia Male:
azoospermia
small testes
cryptorchidism, unilateral or bilateral

Endocrine Features:
hypogonadotropic hypogonadism
low testosterone levels
failure of spontaneous puberty
low luteinizing hormone (lh) levels
apulsatile lh secretion
more
Head And Neck Nose:
anosmia or hyposmia

Genitourinary Kidneys:
unilateral renal aplasia (in some patients)

Genitourinary External Genitalia Male:
micropenis

Head And Neck Face:
facial asymmetry (in some patients)

Genitourinary Internal Genitalia Female:
hypothalamic amenorrhea, functional (in some carrier females)

Neurologic Central Nervous System:
aplasia or hypoplasia of olfactory bulbs
bimanual synkinesia (mirror movements of the hands, in some patients)


Clinical features from OMIM:

308700

Human phenotypes related to Hypogonadotropic Hypogonadism 1 with or Without Anosmia:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 HP:0001251
2 anosmia 31 HP:0000458
3 high palate 31 HP:0000218
4 cryptorchidism 31 HP:0000028
5 pes cavus 31 HP:0001761
6 hypogonadotrophic hypogonadism 31 HP:0000044
7 testicular atrophy 31 HP:0000029
8 decreased testicular size 31 HP:0008734
9 azoospermia 31 HP:0000027
10 gynecomastia 31 HP:0000771
11 facial asymmetry 31 occasional (7.5%) HP:0000324
12 micropenis 31 HP:0000054
13 unilateral renal agenesis 31 HP:0000122
14 sparse pubic hair 31 HP:0002225
15 decreased circulating follicle stimulating hormone level 31 HP:0030341
16 decreased circulating luteinizing hormone level 31 HP:0030344
17 eunuchoid habitus 31 HP:0003782
18 bimanual synkinesia 31 HP:0001335
19 olfactory lobe agenesis 31 HP:0001341
20 leydig cell insensitivity to gonadotropin 31 HP:0002929
21 hypothalamic gonadotropin-releasing hormone deficiency 31 HP:0003164

Drugs & Therapeutics for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

Drugs for Hypogonadotropic Hypogonadism 1 with or Without Anosmia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
rituximab Approved Phase 1 174722-31-7 10201696
2 Antibodies Phase 1
3 Immunoglobulins Phase 1
4
Lopinavir Approved 192725-17-0 92727
5
Ritonavir Approved, Investigational 155213-67-5 392622
6 Anti-HIV Agents
7 Anti-Infective Agents
8 Anti-Retroviral Agents
9 Antiviral Agents
10 Cytochrome P-450 CYP3A Inhibitors
11 Cytochrome P-450 Enzyme Inhibitors
12 HIV Protease Inhibitors
13
protease inhibitors

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Clinical Management of Hereditary Hemochromatosis: Phlebotomy vs. Erythrocytoapheresis Completed NCT00440986 Phase 2, Phase 3
2 Study of Betalutin for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma (LYMRIT-37-05) Recruiting NCT02658968 Phase 1 Betalutin
3 Dosimetry Study of Betalutin for Treatment of Relapsed Non-Hodgkin Lymphoma (LYMRIT-37-02) Not yet recruiting NCT02657447 Phase 1 Betalutin with lilotomab dose 1;Betalutin with lilotomab dose 2
4 A Comparison of CPAP With and Without Humidification: A Pilot Study Completed NCT02423681
5 Long-term Effectiveness and Safety in Hepatitis-co-infected Patients Completed NCT01153269 Lopinavir/Ritonavir (Kaletra)
6 Evaluation of Kaletra Therapy Over the Long-term Completed NCT01083810 Lopinavir/Ritonavir (Kaletra)

Search NIH Clinical Center for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

Genetic Tests for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

Genetic tests related to Hypogonadotropic Hypogonadism 1 with or Without Anosmia:

# Genetic test Affiliating Genes
1 Kallmann Syndrome 1 28 ANOS1

Anatomical Context for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

MalaCards organs/tissues related to Hypogonadotropic Hypogonadism 1 with or Without Anosmia:

38
Pituitary, Olfactory Bulb, Kidney, Eye, Breast, Testes

Publications for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

Articles related to Hypogonadotropic Hypogonadism 1 with or Without Anosmia:

# Title Authors Year
1
ANOS1: a unified nomenclature for Kallmann syndrome 1 gene (KAL1) and anosmin-1. ( 27899353 )
2016
2
Decreased expression of Kallmann syndrome 1 sequence gene (KAL1) contributes to oral squamous cell carcinoma progression and significantly correlates with poorly differentiated grade. ( 25060050 )
2014
3
Kallmann syndrome 1 gene is expressed in the marsupial gonad. ( 21123819 )
2011
4
Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients. ( 15001591 )
2004

Variations for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

UniProtKB/Swiss-Prot genetic disease variations for Hypogonadotropic Hypogonadism 1 with or Without Anosmia:

71 (show all 14)
# Symbol AA change Variation ID SNP ID
1 ANOS1 p.Asn267Lys VAR_007720
2 ANOS1 p.Glu514Lys VAR_012742 rs137852515
3 ANOS1 p.Cys163Tyr VAR_031012
4 ANOS1 p.Cys172Arg VAR_031013
5 ANOS1 p.Arg262Pro VAR_031014
6 ANOS1 p.Asn304Ser VAR_031015 rs140812865
7 ANOS1 p.Ser396Leu VAR_031016 rs137852517
8 ANOS1 p.Phe517Leu VAR_031017
9 ANOS1 p.Trp571Arg VAR_031018
10 ANOS1 p.Cys134Gly VAR_065362
11 ANOS1 p.Cys163Arg VAR_065363
12 ANOS1 p.Glu539Lys VAR_065364 rs144586521
13 ANOS1 p.Val587Leu VAR_069968 rs137900287
14 ANOS1 p.His672Arg VAR_072992 rs199771303

ClinVar genetic disease variations for Hypogonadotropic Hypogonadism 1 with or Without Anosmia:

6 (show all 22)
# Gene Variation Type Significance SNP ID Assembly Location
1 ANOS1 KAL1, 3,300-BP DEL deletion Pathogenic
2 ANOS1 NM_000216.3(ANOS1): c.711G> A (p.Trp237Ter) single nucleotide variant Pathogenic rs137852512 GRCh37 Chromosome X, 8555850: 8555850
3 ANOS1 NM_000216.3(ANOS1): c.769C> T (p.Arg257Ter) single nucleotide variant Pathogenic rs137852513 GRCh37 Chromosome X, 8553395: 8553395
4 ANOS1 NM_000216.3(ANOS1): c.774G> A (p.Trp258Ter) single nucleotide variant Pathogenic rs137852514 GRCh37 Chromosome X, 8553390: 8553390
5 ANOS1 KAL1, 1-BP DEL, PRO277FS deletion Pathogenic
6 ANOS1 KAL1, EX3-5DEL deletion Pathogenic
7 ANOS1 NM_000216.3(ANOS1): c.1540G> A (p.Glu514Lys) single nucleotide variant Pathogenic rs137852515 GRCh37 Chromosome X, 8504893: 8504893
8 ANOS1 KAL1, EX5DEL deletion Pathogenic
9 ANOS1 KAL1, 11-BP DUP, NT158 duplication Pathogenic
10 ANOS1 NM_000216.3(ANOS1): c.784C> T (p.Arg262Ter) single nucleotide variant Pathogenic rs137852516 GRCh37 Chromosome X, 8553380: 8553380
11 ANOS1 KAL1, EX3-13 DEL deletion Pathogenic
12 ANOS1 NM_000216.3(ANOS1): c.1187C> T (p.Ser396Leu) single nucleotide variant Pathogenic rs137852517 GRCh37 Chromosome X, 8536293: 8536293
13 ANOS1 KAL1, EX3-6 DEL deletion Pathogenic
14 ANOS1 NM_000216.3(ANOS1): c.1062+1G> T single nucleotide variant Pathogenic rs387906427 GRCh37 Chromosome X, 8538539: 8538539
15 ANOS1 NM_000216.3(ANOS1): c.1449+2delT deletion Pathogenic rs397518425 GRCh37 Chromosome X, 8507703: 8507703
16 ANOS1 NM_000216.3(ANOS1): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs606231409 GRCh37 Chromosome X, 8700077: 8700077
17 ANOS1 NM_000216.3(ANOS1): c.1904A> C (p.Gln635Pro) single nucleotide variant Likely pathogenic rs1057519418 GRCh37 Chromosome X, 8502440: 8502440
18 ANOS1 NM_000216.3(ANOS1): c.145T> C (p.Cys49Arg) single nucleotide variant Likely pathogenic rs1057520209 GRCh38 Chromosome X, 8731892: 8731892
19 ANOS1 NM_000216.3(ANOS1): c.33_34insA (p.Leu12Thrfs) insertion Pathogenic rs1057520210 GRCh37 Chromosome X, 8700044: 8700045
20 ANOS1 NM_000216.3(ANOS1): c.255+5G> A single nucleotide variant Likely pathogenic rs773138384 GRCh37 Chromosome X, 8667734: 8667734
21 ANOS1 NM_000216.3(ANOS1): c.109G> T (p.Glu37Ter) single nucleotide variant Pathogenic GRCh38 Chromosome X, 8731928: 8731928
22 ANOS1 NM_000216.3(ANOS1): c.1A> T (p.Met1Leu) single nucleotide variant Pathogenic rs606231409 GRCh38 Chromosome X, 8732036: 8732036

Copy number variations for Hypogonadotropic Hypogonadism 1 with or Without Anosmia from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 257179 X 1 9500000 Microdeletion Kallmann Syndrome 1

Expression for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

Search GEO for disease gene expression data for Hypogonadotropic Hypogonadism 1 with or Without Anosmia.

Pathways for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

GO Terms for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

Sources for Hypogonadotropic Hypogonadism 1 with or Without Anosmia

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