{"orpha":478,"name":"Kallmann syndrome","type":"Clinical subtype","group":"Subtype of disorder","status":"active","flags":[],"synonyms":["Congenital hypogonadotropic hypogonadism with anosmia","Olfacto-genital pathological sequence"],"definition":"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).","note":null,"url":"https://raremap.alftech.space/d/ORPHA-478/","orphanet_url":"https://www.orpha.net/en/disease/detail/478","names":{"fr":{"name":"Syndrome de Kallmann","synonyms":["Dysplasie olfacto-génitale de Kallmann-De Morsier","Hypogonadisme hypogonadotrope congénital avec anosmie"],"definition":"Maladie génétique rare du développement caractérisée par l'association d'un hypogonadisme hypogonadotrope congénital (HHC) par déficit en gonadolibérine (GnRH) et d'une anosmie ou hyposmie (avec hypoplasie ou aplasie des bulbes olfactifs)."},"de":{"name":"Kallmann-Syndrom","synonyms":["Kongenitaler hypogonadotroper Hypogonadismus mit Anosmie","Olfaktogenitales Syndrom"],"definition":"Das Kallmann-Syndrom (KS) ist eine erbliche Entwicklungsstörung mit kongenitalem hypogonadotropem Hypogonadismus (CHH) aufgrund eines Gonadotropin-Releasing-Hormon (GnRH)-Mangels und mit Anosmie oder Hyposmie (bei Hypoplasie oder Aplasie der Riechkolben)."},"es":{"name":"Síndrome de Kallmann","synonyms":["Hipogonadismo hipogonadotrópico congénito con anosmia","Secuencia patológica olfato-genital"],"definition":"El síndrome de Kallmann (KS) es una enfermedad genética del desarrollo que se caracteriza por la asociación de un hipogonadismo hipogonadotrófico (CHH) congénito por déficit de hormona liberadora de gonadotropina (GnRH) y anosmia o hiposmia (con hipoplasia o aplasia de los bulbos olfativos)."},"it":{"name":"Sindrome di Kallmann","synonyms":["Ipogonadismo ipogonadotropo congenito con anosmia","Sequenza patologica olfatto-genitale"],"definition":"La sindrome di Kallmann (KS) è una patologia genetica dello sviluppo, che associa ipogonadismo ipogonadotropo congenito (CHH) da deficit dell'ormone di rilascio delle gonadotropine (GnRH), anosmia o iposmia (con ipoplasia o aplasia dei bulbi olfattivi)."},"nl":{"name":"Syndroom van Kallmann","synonyms":["Congenitaal hypogonadotroop hypogonadisme met anosmie","Olfacto-genitale pathologische sequentie"],"definition":"Kallmansyndroom (KS) is een genetische ontwikkelingsstoornis die gekenmerkt wordt door de associatie van congenitaal hypogonadotropisch hypogonadisme (CHH) als gevolg van gonadotropine-releasing hormoon (GnRH)-deficiëntie, en anosmie of hyposmie (met hypoplasie of aplasie van de bulbus olfactorius)."},"pt":{"name":"Síndrome Kallmann","synonyms":["Sequência patológica olfato-genital","Síndrome de hipogonadismo hipogonadotrópico congénito com anosmia"],"definition":"O síndrome de Kallmann (KS) é uma doença genética congénita caracterizada pela associação de hipogonadismo hipogonadotrófico (HH) por deficiência da hormona libertadora de gonadotropina (GnRH), e anosmia ou hiposmia (com hipoplasia ou aplasia do bolbo olfactivo)."},"pl":{"name":"Zespół Kallmanna","synonyms":["Patologiczna sekwencja węchowo-płciowa","Wrodzony hipogonadyzm hipogonadotropowy z anosmią"]},"cs":{"name":"Kallmannův syndrom","synonyms":["Vrozený hypogonadotropní hypogonadismus s anosmií","Olfaktogenitální patologická sekvence"]},"uk":{"name":"Синдром Калмана","synonyms":["Вроджений гіпогонадотропний гіпогонадизм з аносмією","Ольфакто-генітальна патологічна послідовність"],"definition":"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)."},"zh":{"name":"Kallmann综合征","synonyms":["先天性低促性腺激素性功能减退症伴嗅觉丧失"]},"tr":{"name":"Kallmann sendromu","synonyms":["Olfakto-genital patolojik dizi","Anosmili Doğumsal hipogonadotropik hipogonadizm"]}},"xrefs":[{"source":"OMIM","code":"147950","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"OMIM","code":"244200","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"308700","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"610628","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"612370","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"612702","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614837","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614838","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614840","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614858","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614880","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614897","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"615266","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"615267","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"615269","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"615270","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"615271","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"616030","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618841","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E23.0","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"5A61.2","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1409526590"},{"source":"MONDO","code":"0018800","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D017436","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0162809","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"10771","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10053142","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":97978,"name":"Rare endocrine disease"},"parents":[{"orpha":238666,"name":"Isolated congenital hypogonadotropic hypogonadism","classifications":[156,193,201,205]}],"children":[],"genes":[{"symbol":"ANOS1","name":"anosmin 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"21168128[PMID]","hgnc":"6211","ensembl":"ENSG00000011201","omim":"300836","loci":["Xp22.31"]},{"symbol":"DCC","name":"DCC netrin 1 receptor","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"29202173[PMID]","hgnc":"2701","ensembl":"ENSG00000187323","omim":"120470","loci":["18q21.2"]},{"symbol":"FEZF1","name":"FEZ family zinc finger 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"25192046[PMID]","hgnc":"22788","ensembl":"ENSG00000128610","omim":"613301","loci":["7q31.32"]},{"symbol":"FGF8","name":"fibroblast growth factor 8","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"18596921[PMID]_20463092[PMID]","hgnc":"3686","ensembl":"ENSG00000107831","omim":"600483","loci":["10q24.32"]},{"symbol":"FGFR1","name":"fibroblast growth factor receptor 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"17235395[PMID]","hgnc":"3688","ensembl":"ENSG00000077782","omim":"136350","loci":["8p11.23"]},{"symbol":"HS6ST1","name":"heparan sulfate 6-O-sulfotransferase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"21700882[PMID]_23997646[PMID]","hgnc":"5201","ensembl":"ENSG00000136720","omim":"604846","loci":["2q14.3"]},{"symbol":"PROK2","name":"prokineticin 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"18682503[PMID]","hgnc":"18455","ensembl":"ENSG00000163421","omim":"607002","loci":["3p13"]},{"symbol":"PROKR2","name":"prokineticin receptor 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"18682503[PMID]","hgnc":"15836","ensembl":"ENSG00000101292","omim":"607123","loci":["20p12.3"]},{"symbol":"SEMA3A","name":"semaphorin 3A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"22416012[PMID]","hgnc":"10723","ensembl":"ENSG00000075213","omim":"603961","loci":["7q21.11"]},{"symbol":"SOX10","name":"SRY-box transcription factor 10","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"23643381[PMID]","hgnc":"11190","ensembl":"ENSG00000100146","omim":"602229","loci":["22q13.1"]},{"symbol":"CCDC141","name":"coiled-coil domain containing 141","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"28324054[PMID]","hgnc":"26821","ensembl":"ENSG00000163492","omim":"616031","loci":["2q31.2"]},{"symbol":"CHD7","name":"chromodomain helicase DNA binding protein 7","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"18834967[PMID]","hgnc":"20626","ensembl":"ENSG00000171316","omim":"608892","loci":["8q12.2"]},{"symbol":"DUSP6","name":"dual specificity phosphatase 6","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23643382[PMID]","hgnc":"3072","ensembl":"ENSG00000139318","omim":"602748","loci":["12q21.33"]},{"symbol":"EMX2","name":"empty spiracles homeobox 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"41765865[PMID]","hgnc":"3341","ensembl":"ENSG00000170370","omim":"600035","loci":["10q26.11"]},{"symbol":"FGF17","name":"fibroblast growth factor 17","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23643382[PMID]","hgnc":"3673","ensembl":"ENSG00000158815","omim":"603725","loci":["8p21.3"]},{"symbol":"FLRT3","name":"fibronectin leucine rich transmembrane protein 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23643382[PMID]","hgnc":"3762","ensembl":"ENSG00000125848","omim":"604808","loci":["20p12.1"]},{"symbol":"HESX1","name":"HESX homeobox 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23465708[PMID]","hgnc":"4877","ensembl":"ENSG00000163666","omim":"601802","loci":["3p14.3"]},{"symbol":"IL17RD","name":"interleukin 17 receptor D","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23643382[PMID]","hgnc":"17616","ensembl":"ENSG00000144730","omim":"606807","loci":["3p14.3"]},{"symbol":"NDNF","name":"neuron derived neurotrophic factor","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"31883645[PMID]","hgnc":"26256","ensembl":"ENSG00000173376","omim":"616506","loci":["4q27"]},{"symbol":"SPRY4","name":"sprouty RTK signaling antagonist 4","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23643382[PMID]","hgnc":"15533","ensembl":"ENSG00000187678","omim":"607984","loci":["5q31.3"]},{"symbol":"TACR3","name":"tachykinin receptor 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23643382[PMID]_19079066[PMID]","hgnc":"11528","ensembl":"ENSG00000169836","omim":"162332","loci":["4q24"]},{"symbol":"WDR11","name":"WD repeat domain 11","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20887964[PMID]","hgnc":"13831","ensembl":"ENSG00000120008","omim":"606417","loci":["10q26.12"]},{"symbol":"CCDC141","name":"coiled-coil domain containing 141","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Assessed","source":"28324054[PMID]","hgnc":"26821","ensembl":"ENSG00000163492","omim":"616031","loci":["2q31.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant","Autosomal recessive","Multigenic/multifactorial","X-linked recessive"],"onset":["Adolescent","Childhood"],"prevalence":[{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 100 000","value":3.75,"area":"Europe","status":"Validated","source":"[EXPERT]"},{"type":"Annual incidence","qualification":"Value and class","class":"1-9 / 100 000","value":5.0,"area":"France","status":"Validated","source":"4147392[PMID]"},{"type":"Annual incidence","qualification":"Value and class","class":"1-9 / 100 000","value":2.1,"area":"Finland","status":"Validated","source":"21682876[PMID]"},{"type":"Annual incidence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.6,"area":"Specific population","status":"Validated","source":"3791676[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0000458","label":"Anosmia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000830","label":"Anterior hypopituitarism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000144","label":"Decreased fertility","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008734","label":"Decreased testicular size","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000823","label":"Delayed puberty","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0100639","label":"Erectile dysfunction","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000044","label":"Hypogonadotropic hypogonadism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008736","label":"Hypoplasia of penis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004409","label":"Hyposmia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003164","label":"Hypothalamic gonadotropin-releasing hormone (GNRH) deficiency","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000054","label":"Micropenis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001608","label":"Abnormality of the voice","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003187","label":"Breast hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004349","label":"Reduced bone mineral density","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030680","label":"Abnormal cardiovascular system morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000008","label":"Abnormal morphology of female internal genitalia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001335","label":"Bimanual synkinesia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000175","label":"Cleft palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000551","label":"Color vision defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002750","label":"Delayed skeletal maturation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030016","label":"Dyspareunia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000771","label":"Gynecomastia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008064","label":"Ichthyosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001513","label":"Obesity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010550","label":"Paraplegia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001761","label":"Pes cavus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001763","label":"Pes planus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000786","label":"Primary amenorrhea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002757","label":"Recurrent fractures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000104","label":"Renal agenesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002652","label":"Skeletal dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009804","label":"Tooth agenesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001337","label":"Tremor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000505","label":"Visual impairment","frequency":"Occasional (29-5%)","criteria":null}]}}