ORPHA:478
Kallmann syndrome
Synonyms: Congenital hypogonadotropic hypogonadism with anosmia · Olfacto-genital pathological sequence
- Type
- Clinical subtype
- Group
- Subtype of disorder
- Inheritance
- Autosomal dominant, Autosomal recessive, Multigenic/multifactorial, X-linked recessive
- Age of onset
- Adolescent, Childhood
- Status
- active
Kallmann syndrome (KS) is a developmental genetic disorder characterized by the association of congenital hypogonadotropic hypogonadism (CHH) due to gonadotropin-releasing hormone (GnRH) deficiency, and anosmia or hyposmia (with hypoplasia or aplasia of the olfactory bulbs).
1
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Kallmann syndrome | Congenital hypogonadotropic hypogonadism with anosmia · Olfacto-genital pathological sequence |
| fr | Syndrome de Kallmann | Dysplasie olfacto-génitale de Kallmann-De Morsier · Hypogonadisme hypogonadotrope congénital avec anosmie |
| de | Kallmann-Syndrom | Kongenitaler hypogonadotroper Hypogonadismus mit Anosmie · Olfaktogenitales Syndrom |
| es | Síndrome de Kallmann | Hipogonadismo hipogonadotrópico congénito con anosmia · Secuencia patológica olfato-genital |
| it | Sindrome di Kallmann | Ipogonadismo ipogonadotropo congenito con anosmia · Sequenza patologica olfatto-genitale |
| nl | Syndroom van Kallmann | Congenitaal hypogonadotroop hypogonadisme met anosmie · Olfacto-genitale pathologische sequentie |
| pt | Síndrome Kallmann | Sequência patológica olfato-genital · Síndrome de hipogonadismo hipogonadotrópico congénito com anosmia |
| pl | Zespół Kallmanna | Patologiczna sekwencja węchowo-płciowa · Wrodzony hipogonadyzm hipogonadotropowy z anosmią |
| cs | Kallmannův syndrom | Vrozený hypogonadotropní hypogonadismus s anosmií · Olfaktogenitální patologická sekvence |
| uk | Синдром Калмана | Вроджений гіпогонадотропний гіпогонадизм з аносмією · Ольфакто-генітальна патологічна послідовність |
| zh | Kallmann综合征 | 先天性低促性腺激素性功能减退症伴嗅觉丧失 |
| tr | Kallmann sendromu | Olfakto-genital patolojik dizi · Anosmili Doğumsal hipogonadotropik hipogonadizm |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 147950 | NTBT | validated | |
| OMIM | 244200 | BTNT | validated | |
| OMIM | 308700 | BTNT | validated | |
| OMIM | 610628 | BTNT | validated | |
| OMIM | 612370 | BTNT | validated | |
| OMIM | 612702 | BTNT | validated | |
| OMIM | 614837 | BTNT | validated | |
| OMIM | 614838 | BTNT | validated | |
| OMIM | 614840 | BTNT | validated | |
| OMIM | 614858 | BTNT | validated | |
| OMIM | 614880 | BTNT | validated | |
| OMIM | 614897 | BTNT | validated | |
| OMIM | 615266 | BTNT | validated | |
| OMIM | 615267 | BTNT | validated | |
| OMIM | 615269 | BTNT | validated | |
| OMIM | 615270 | BTNT | validated | |
| OMIM | 615271 | BTNT | validated | |
| OMIM | 616030 | BTNT | validated | |
| OMIM | 618841 | BTNT | validated | |
| ICD-10 | E23.0 | NTBT | inclusion | validated |
| ICD-11 | 5A61.2 | NTBT | index | validated |
| MONDO | 0018800 | E | validated | |
| MeSH | D017436 | E | validated | |
| UMLS | C0162809 | E | validated | |
| GARD | 10771 | E | validated | |
| MedDRA | 10053142 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
3
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (1):
- ORPHA:238666Isolated congenital hypogonadotropic hypogonadism
rare genetic diseases; rare endocrine diseases; rare infertility disorders; rare gynecological and obstetric diseases
No children.
4
Genes
23 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| ANOS1 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:6211 | ENSG00000011201 | 300836 | Xp22.31 | anosmin 1 | 21168128[PMID] |
| DCC | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:2701 | ENSG00000187323 | 120470 | 18q21.2 | DCC netrin 1 receptor | 29202173[PMID] |
| FEZF1 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:22788 | ENSG00000128610 | 613301 | 7q31.32 | FEZ family zinc finger 1 | 25192046[PMID] |
| FGF8 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:3686 | ENSG00000107831 | 600483 | 10q24.32 | fibroblast growth factor 8 | 18596921[PMID]_20463092[PMID] |
| FGFR1 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:3688 | ENSG00000077782 | 136350 | 8p11.23 | fibroblast growth factor receptor 1 | 17235395[PMID] |
| HS6ST1 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:5201 | ENSG00000136720 | 604846 | 2q14.3 | heparan sulfate 6-O-sulfotransferase 1 | 21700882[PMID]_23997646[PMID] |
| PROK2 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:18455 | ENSG00000163421 | 607002 | 3p13 | prokineticin 2 | 18682503[PMID] |
| PROKR2 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:15836 | ENSG00000101292 | 607123 | 20p12.3 | prokineticin receptor 2 | 18682503[PMID] |
| SEMA3A | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:10723 | ENSG00000075213 | 603961 | 7q21.11 | semaphorin 3A | 22416012[PMID] |
| SOX10 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:11190 | ENSG00000100146 | 602229 | 22q13.1 | SRY-box transcription factor 10 | 23643381[PMID] |
| CCDC141 | Disease-causing germline mutation(s) in | Assessed | HGNC:26821 | ENSG00000163492 | 616031 | 2q31.2 | coiled-coil domain containing 141 | 28324054[PMID] |
| CHD7 | Disease-causing germline mutation(s) in | Assessed | HGNC:20626 | ENSG00000171316 | 608892 | 8q12.2 | chromodomain helicase DNA binding protein 7 | 18834967[PMID] |
| DUSP6 | Disease-causing germline mutation(s) in | Assessed | HGNC:3072 | ENSG00000139318 | 602748 | 12q21.33 | dual specificity phosphatase 6 | 23643382[PMID] |
| EMX2 | Disease-causing germline mutation(s) in | Assessed | HGNC:3341 | ENSG00000170370 | 600035 | 10q26.11 | empty spiracles homeobox 2 | 41765865[PMID] |
| FGF17 | Disease-causing germline mutation(s) in | Assessed | HGNC:3673 | ENSG00000158815 | 603725 | 8p21.3 | fibroblast growth factor 17 | 23643382[PMID] |
| FLRT3 | Disease-causing germline mutation(s) in | Assessed | HGNC:3762 | ENSG00000125848 | 604808 | 20p12.1 | fibronectin leucine rich transmembrane protein 3 | 23643382[PMID] |
| HESX1 | Disease-causing germline mutation(s) in | Assessed | HGNC:4877 | ENSG00000163666 | 601802 | 3p14.3 | HESX homeobox 1 | 23465708[PMID] |
| IL17RD | Disease-causing germline mutation(s) in | Assessed | HGNC:17616 | ENSG00000144730 | 606807 | 3p14.3 | interleukin 17 receptor D | 23643382[PMID] |
| NDNF | Disease-causing germline mutation(s) in | Assessed | HGNC:26256 | ENSG00000173376 | 616506 | 4q27 | neuron derived neurotrophic factor | 31883645[PMID] |
| SPRY4 | Disease-causing germline mutation(s) in | Assessed | HGNC:15533 | ENSG00000187678 | 607984 | 5q31.3 | sprouty RTK signaling antagonist 4 | 23643382[PMID] |
| TACR3 | Disease-causing germline mutation(s) in | Assessed | HGNC:11528 | ENSG00000169836 | 162332 | 4q24 | tachykinin receptor 3 | 23643382[PMID]_19079066[PMID] |
| WDR11 | Disease-causing germline mutation(s) in | Assessed | HGNC:13831 | ENSG00000120008 | 606417 | 10q26.12 | WD repeat domain 11 | 20887964[PMID] |
| CCDC141 | Major susceptibility factor in | Assessed | HGNC:26821 | ENSG00000163492 | 616031 | 2q31.2 | coiled-coil domain containing 141 | 28324054[PMID] |
5
Prevalence and incidence
4 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Point prevalence | 1-9 / 100 000 | 3.75 / 100 000 | Europe | Value and class | Validated | [EXPERT] |
| Annual incidence | 1-9 / 100 000 | 5 / 100 000 | France | Value and class | Validated | 4147392[PMID] |
| Annual incidence | 1-9 / 100 000 | 2.1 / 100 000 | Finland | Value and class | Validated | 21682876[PMID] |
| Annual incidence | 1-9 / 1 000 000 | 0.6 / 100 000 | Specific population | Value and class | Validated | 3791676[PMID] |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
6
HPO phenotypes
44 annotations · validated 2016-06-01| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0000458 | Anosmia | |
| HP:0000830 | Anterior hypopituitarism | |
| HP:0000144 | Decreased fertility | |
| HP:0008734 | Decreased testicular size | |
| HP:0000823 | Delayed puberty | |
| HP:0100639 | Erectile dysfunction | |
| HP:0000044 | Hypogonadotropic hypogonadism | |
| HP:0008736 | Hypoplasia of penis | |
| HP:0004409 | Hyposmia | |
| HP:0003164 | Hypothalamic gonadotropin-releasing hormone (GNRH) deficiency | |
| HP:0000054 | Micropenis | |
| Frequent (79-30%) | ||
| HP:0001608 | Abnormality of the voice | |
| HP:0003187 | Breast hypoplasia | |
| HP:0000028 | Cryptorchidism | |
| HP:0004349 | Reduced bone mineral density | |
| Occasional (29-5%) | ||
| HP:0030680 | Abnormal cardiovascular system morphology | |
| HP:0000008 | Abnormal morphology of female internal genitalia | |
| HP:0001251 | Ataxia | |
| HP:0001335 | Bimanual synkinesia | |
| HP:0000175 | Cleft palate | |
| HP:0000551 | Color vision defect | |
| HP:0002750 | Delayed skeletal maturation | |
| HP:0001260 | Dysarthria | |
| HP:0030016 | Dyspareunia | |
| HP:0001288 | Gait disturbance | |
| HP:0000771 | Gynecomastia | |
| HP:0001252 | Hypotonia | |
| HP:0008064 | Ichthyosis | |
| HP:0001324 | Muscle weakness | |
| HP:0000639 | Nystagmus | |
| HP:0001513 | Obesity | |
| HP:0010550 | Paraplegia | |
| HP:0001761 | Pes cavus | |
| HP:0001763 | Pes planus | |
| HP:0000786 | Primary amenorrhea | |
| HP:0000508 | Ptosis | |
| HP:0002757 | Recurrent fractures | |
| HP:0000104 | Renal agenesis | |
| HP:0001250 | Seizure | |
| HP:0000407 | Sensorineural hearing impairment | |
| HP:0002652 | Skeletal dysplasia | |
| HP:0009804 | Tooth agenesis | |
| HP:0001337 | Tremor | |
| HP:0000505 | Visual impairment | |
Run the differential on the 11 obligate / very frequent terms
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/478
- This record as JSON: /data/d/478.json