{"orpha":447896,"name":"Tremor-ataxia-central hypomyelination syndrome","type":"Clinical subtype","group":"Subtype of disorder","status":"active","flags":[],"synonyms":["TACH syndrome"],"definition":null,"note":"This disease is described under 4H leukodystrophy","url":"https://raremap.alftech.space/d/ORPHA-447896/","orphanet_url":"https://www.orpha.net/en/disease/detail/447896","names":{"fr":{"name":"Syndrome de tremblement-ataxie-hypomyélinisation centrale","synonyms":["Syndrome TACH"]},"de":{"name":"Tremor-Ataxie-zentrale Hypomyelinisierung-Syndrom","synonyms":["TACH"]},"es":{"name":"Síndrome de temblor-ataxia-hipomielinización central","synonyms":["TACH"]},"it":{"name":"Sindrome tremore-atassia-ipomielinizzazione centrale","synonyms":["TACH"]},"nl":{"name":"Tremor - ataxie - centrale hypomyelinisatie-syndroom","synonyms":["TACH"]},"pt":{"name":"Síndrome de tremor – ataxia – hipomielinização central"},"pl":{"name":"Zespół drżenia, ataksji i hipomielinizacji ośrodkowej","synonyms":["TACH"]},"cs":{"name":"Syndrom zahrnující tremor, ataxii a centrální hypomyelinizaci","synonyms":["TACH syndrom"]},"uk":{"name":"Синдром тремору-атаксії-центральної гіпомієлінізації","synonyms":["Синдром тахікардії"]},"zh":{"name":"震颤性共济失调伴中枢性髓鞘发育落后综合征","synonyms":["TACH综合征"]},"tr":{"name":"Tremor-ataksi-santral hipomiyelinasyon sendromu","synonyms":["TACH sendromu"]}},"xrefs":[{"source":"OMIM","code":"607694","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E75.2","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0018656","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5680067","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":289494,"name":"4H leukodystrophy","classifications":[156,181]},{"orpha":183518,"name":"Hereditary ataxia","classifications":[156,181]},{"orpha":441434,"name":"Syndromic hereditary optic neuropathy","classifications":[156,189]}],"children":[],"genes":[{"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"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Childhood","Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":7.0,"area":"Worldwide","status":"Validated","source":"20640464[PMID]_22384513[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_20640464[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2018-05-02","source":"20640464[PMID]_17159124[PMID]_22036171[PMID]_17712733[PMID]_15851747[PMID]_12605447[PMID]","terms":[{"hpo":"HP:0002134","label":"Abnormal basal ganglia morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000617","label":"Abnormality of ocular smooth pursuit","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005341","label":"Autonomic bladder dysfunction","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003487","label":"Babinski sign","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003429","label":"CNS hypomyelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002312","label":"Clumsiness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000684","label":"Delayed eruption of teeth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000823","label":"Delayed puberty","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001310","label":"Dysmetria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025460","label":"High myoinositol in brain by MRS","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000668","label":"Hypodontia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000044","label":"Hypogonadotropic hypogonadism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001256","label":"Intellectual disability, mild","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002080","label":"Intention tremor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002415","label":"Leukodystrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000677","label":"Oligodontia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002403","label":"Positive Romberg sign","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002174","label":"Postural tremor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002464","label":"Spastic dysarthria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002493","label":"Upper motor neuron dysfunction","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000511","label":"Vertical supranuclear gaze palsy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002307","label":"Drooling","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006858","label":"Impaired distal proprioception","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002166","label":"Impaired vibration sensation in the lower limbs","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009830","label":"Peripheral neuropathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000490","label":"Deeply set eye","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0007359","label":"Focal-onset seizure","frequency":"Very rare (<4-1%)","criteria":null}]}}