{"orpha":289494,"name":"4H leukodystrophy","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["POLR-related leukodystrophy"],"definition":"A rare hypomyelinating leukodystrophy disorder characterized by the association of dental abnormalities (delayed dentition, abnormal order of dentition, hypodontia), hypogonadotropic hypogonadism, and hypomyelinating leukodystrophy manifesting with neurodevelopmental delay or regression and/or progressive cerebellar symptoms.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-289494/","orphanet_url":"https://www.orpha.net/en/disease/detail/289494","names":{"fr":{"name":"Leucodystrophie 4H","synonyms":["Leucodystrophie hypomyélinisante associée à POLR"],"definition":"Leucodystrophie hypomyélinisante rare caractérisée par l'association d'anomalies dentaires (retard d'éruption de dents, anomalies dans l'ordre d'éruption de dents, hypodontie), d'hypogonadisme hypogonadotrope et de leucodystrophie hypomyélinisante se manifestant par un retard neurodéveloppemental avec régression et/ou des signes d'atteinte cérébelleuse progressive."},"de":{"name":"4H-Leukodystrophie","synonyms":["4H-Syndrom","POLR-assoziierte Leukodystrophie"],"definition":"Eine seltene neurologische Erkrankung aus der Gruppe der Leukodystrophien, die durch die Assoziation von Zahnanomalien (verzögertes Gebiss, abnorme Zahnreihenfolge, Hypodontie), hypogonadotropem Hypogonadismus und hypomyelinisierender Leukodystrophie gekennzeichnet ist, die sich in einer Verzögerung oder Regression der neurologischen Entwicklung und/oder progressiven zerebellären Symptomen manifestiert."},"es":{"name":"Leucodistrofia 4H","synonyms":["Leucodistrofia asociada a POLR"],"definition":"Es una leucodistrofia hipomielinizante poco frecuente caracterizada por la asociación de anomalías dentales (retraso en la dentición, orden anómalo de la dentición, hipodontia), hipogonadismo hipogonadotrópico y leucodistrofia hipomielinizante que se manifiesta como retraso o regresión del neurodesarrollo y/o síntomas cerebelosos progresivos."},"it":{"name":"Leucodistrofia 4H","synonyms":["Leucodistrofia Pol III-correlata"],"definition":"Si tratta di una leucodistrofia ipomielinizzante rara, caratterizzata da anomalie dei denti (ritardo della dentizione, anomalie nell'ordine di eruzione dei denti, ipodontia), ipogonadismo ipogonadotropo e leucodistrofia ipomielinizzante che si manifesta con ritardo dello sviluppo neurologico o regressione e/o sintomi cerebellari progressivi."},"nl":{"name":"4H-leukodystrofie","synonyms":["POLR-gerelateerde leukodystrofie"],"definition":"Een zeldzame hypomyeliniserende leukodystrofie, gekarakteriseerd door de associatie van tandanomalieën (vertraagde tanderuptie, abnormale volgorde van tanderuptie, hypodontie), hypogonadotroop hypogonadisme, en hypomyeliniserende leukodystrofie die zich manifesteert met neurologische ontwikkelingsachterstand of -regressie en/of progressieve cerebellaire symptomen."},"pt":{"name":"Leucodistrofia hipomielinizante com ou sem oligondontia e/ou hipogonadismo"},"pl":{"name":"Leukodystrofia hipomielinizująca z lub bez oligodoncji i/lub hipogonadyzmem","synonyms":["Leukodystrofia związna z Pol III"]},"cs":{"name":"Hypomyelinizační leukodystrofie s/bez oligodontie a/nebo hypogonadizmem","synonyms":["Pol III-vázaná leukodystrofie"]},"uk":{"name":"4H лейкодистрофія","synonyms":["POLR-асоційована лейкодистрофія"],"definition":"A rare hypomyelinating leukodystrophy disorder characterized by the association of dental abnormalities (delayed dentition, abnormal order of dentition, hypodontia), hypogonadotropic hypogonadism, and hypomyelinating leukodystrophy manifesting with neurodevelopmental delay or regression and/or progressive cerebellar symptoms."},"zh":{"name":"4H型脑白质营养不良","synonyms":["POLR相关脑白质营养不良"],"definition":"一种罕见的髓鞘脑白质营养不良，其特征是牙齿异常（出牙延迟、牙列顺序异常、缺牙症）、低促性腺素性功能减退症和以神经发育迟缓或退化性和/或进行性小脑症状为表现的髓鞘脑白质营养不良。"},"tr":{"name":"4H lökodistrofi","synonyms":["POLR-ilişkili lökodistrofi"]}},"xrefs":[{"source":"OMIM","code":"607694","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614381","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"616494","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G37.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"8A44.Z","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1151136209"},{"source":"MONDO","code":"100605","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5679947","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":68356,"name":"Leukodystrophy","classifications":[156,181]}],"children":[{"orpha":137639,"name":"Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome","type":"Clinical subtype"},{"orpha":447893,"name":"Hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome","type":"Clinical subtype"},{"orpha":88637,"name":"Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome","type":"Clinical subtype"},{"orpha":77295,"name":"Odontoleukodystrophy","type":"Clinical subtype"},{"orpha":447896,"name":"Tremor-ataxia-central hypomyelination syndrome","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"POLR1C","name":"RNA polymerase I and III subunit C","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"26151409[PMID]","hgnc":"20194","ensembl":"ENSG00000171453","omim":"610060","loci":["6p21.1"],"via":{"orpha":88637,"name":"Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome"}},{"symbol":"POLR3A","name":"RNA polymerase III subunit A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21855841[PMID]_22855961[PMID]","hgnc":"30074","ensembl":"ENSG00000148606","omim":"614258","loci":["10q22.3"],"via":{"orpha":77295,"name":"Odontoleukodystrophy"}},{"symbol":"POLR3A","name":"RNA polymerase III subunit A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21855841[PMID]_22855961[PMID]","hgnc":"30074","ensembl":"ENSG00000148606","omim":"614258","loci":["10q22.3"],"via":{"orpha":88637,"name":"Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome"}},{"symbol":"POLR3A","name":"RNA polymerase III subunit A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"27506977[PMID]","hgnc":"30074","ensembl":"ENSG00000148606","omim":"614258","loci":["10q22.3"],"via":{"orpha":137639,"name":"Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome"}},{"symbol":"POLR3A","name":"RNA polymerase III subunit A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22036171[PMID]","hgnc":"30074","ensembl":"ENSG00000148606","omim":"614258","loci":["10q22.3"],"via":{"orpha":447893,"name":"Hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome"}},{"symbol":"POLR3A","name":"RNA polymerase III subunit A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20640464[PMID]","hgnc":"30074","ensembl":"ENSG00000148606","omim":"614258","loci":["10q22.3"],"via":{"orpha":447896,"name":"Tremor-ataxia-central hypomyelination syndrome"}},{"symbol":"POLR3B","name":"RNA polymerase III subunit B","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22855961[PMID]_22036172[PMID]","hgnc":"30348","ensembl":"ENSG00000013503","omim":"614366","loci":["12q23.3"],"via":{"orpha":88637,"name":"Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome"}}],"inheritance":[],"onset":["Adolescent","Adult","Childhood","Infancy"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_[EXPERT]"},{"type":"Cases/families","qualification":"Case(s)","class":null,"value":200.0,"area":"Worldwide","status":"Validated","source":"[EXPERT]_22855961[PMID]_25339210[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2021-03-31","source":"22855961[PMID]_33005949[PMID]_31768296[PMID]","terms":[{"hpo":"HP:0000164","label":"Abnormality of the dentition","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0006808","label":"Cerebral hypomyelination","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000668","label":"Hypodontia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000044","label":"Hypogonadotropic hypogonadism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002071","label":"Abnormality of extrapyramidal motor function","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000496","label":"Abnormality of eye movement","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000823","label":"Delayed puberty","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002307","label":"Drooling","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030890","label":"Hyperintensity of cerebral white matter on MRI","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007240","label":"Progressive gait ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001337","label":"Tremor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002493","label":"Upper motor neuron dysfunction","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000570","label":"Abnormal saccadic eye movements","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002926","label":"Abnormality of thyroid physiology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000824","label":"Decreased response to growth hormone stimulation test","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000684","label":"Delayed eruption of teeth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002075","label":"Dysdiadochokinesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001310","label":"Dysmetria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000640","label":"Gaze-evoked nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001268","label":"Mental deterioration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0031206","label":"Striatal T2 hyperintensity","frequency":"Very rare (<4-1%)","criteria":null}]}}