{"orpha":2254,"name":"Pontocerebellar hypoplasia type 1","type":"Clinical subtype","group":"Subtype of disorder","status":"active","flags":[],"synonyms":["Norman disease","PCH1"],"definition":"A severe, genetic form of pontocerebellar hypoplasia (PCH) characterized by spinal cord anterior horn cell degeneration in addition to pontocerebellar hypoplasia. Clinically, patients manifest with a severe global development deficit that is evident early on from difficulties in feeding and swallowing","note":null,"url":"https://raremap.alftech.space/d/ORPHA-2254/","orphanet_url":"https://www.orpha.net/en/disease/detail/2254","names":{"fr":{"name":"Hypoplasie pontocérébelleuse type 1","synonyms":["HPC1","PCH1"],"definition":"Forme génétique sévère d'hypoplasie pontocérébelleuse (PCH) caractérisée par une dégénérescence des cellules de la corne antérieure de la moelle épinière associée à une hypoplasie pontocérébelleuse. Sur le plan clinique, les patients présentent un grave retard global de développement qui se manifeste très tôt par des troubles de la déglutition entraînant des difficultés à s'alimenter."},"de":{"name":"Pontozerebelläre Hypoplasie Typ 1","synonyms":["Norman-Krankheit","PCH1"],"definition":"Eine schwere genetisch bedingte Form der pontozerebellären Hypoplasie (PCH), die durch eine Degeneration der anterioren Hornzellen des Rückenmarks zusätzlich zur pontozerebellären Hypoplasie gekennzeichnet ist. Klinisch zeigen die Patienten eine schwere globale Entwicklungsverzögerung, die sich früh durch Schwierigkeiten bei der Nahrungsaufnahme und beim Schlucken bemerkbar macht."},"es":{"name":"Hipoplasia pontocerebelosa tipo 1","synonyms":["Enfermedad de Norman","HPC1"],"definition":"Es una forma genética grave de hipoplasia pontocerebelosa (HPC) caracterizada por la degeneración de las células del asta anterior de la médula espinal acompañada de hipoplasia pontocerebelosa. Clínicamente, los pacientes presentan un grave déficit del desarrollo global que se manifiesta precozmente como dificultades en la alimentación y la deglución."},"it":{"name":"Ipoplasia pontocerebellare, tipo 1","synonyms":["Malattia di Norman","PCH1"],"definition":"L'ipoplasia pontocerebellare tipo 1 (PCH1) è una forma genetica grave di ipoplasia pontocerebellare (PCH), caratterizzata dalla degenerazione delle cellule delle corna anteriori del midollo spinale, associata ad ipoplasia pontocerebellare. Dal punto di vista clinico, i pazienti presentano un grave deficit dello sviluppo globale, che si manifesta precocemente con difficoltà di alimentazione e deglutizione."},"nl":{"name":"Pontocerebellaire hypoplasie type 1","synonyms":["PCH1","Ziekte van Norman"],"definition":"Een ernstige, genetische vorm van pontocerebellaire hypoplasie (PCH), gekenmerkt door degeneratie van voorhoorncellen van ruggenmerg, bovenop pontocerebellaire hypoplasie. Klinisch vertonen patiënten ernstige algehele ontwikkelingsachterstand die al vroeg merkbaar is door problemen met voedings- en slikproblemen."},"pt":{"name":"Hipoplasia pontocerebelosa tipo 1"},"pl":{"name":"Hipolplazja mostu i móżdżku typu 1","synonyms":["Choroba Normana","PCH1"]},"cs":{"name":"Pontocerebelární hypoplázie, typ 1","synonyms":["Normanova nemoc","PCH1"]},"uk":{"name":"Гіпоплазія мозочка, тип 1","synonyms":["Хвороба Нормана","PCH1"],"definition":"A severe, genetic form of pontocerebellar hypoplasia (PCH) characterized by spinal cord anterior horn cell degeneration in addition to pontocerebellar hypoplasia. Clinically, patients manifest with a severe global development deficit that is evident early on from difficulties in feeding and swallowing"},"zh":{"name":"脑桥小脑发育不全1型","synonyms":["Norman 病"]},"tr":{"name":"Pontoserebellar hipoplazi tip 1","synonyms":["PCH1","Norman hastalığı"]}},"xrefs":[{"source":"OMIM","code":"607596","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614678","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"616081","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618065","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"619303","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"619304","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q04.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD20.01","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1227773923"},{"source":"MONDO","code":"0016396","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C548069","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5442006","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"10704","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":98523,"name":"Pontocerebellar hypoplasia","classifications":[147,156,181]},{"orpha":207012,"name":"Spinal muscular atrophy associated with central nervous system anomaly","classifications":[156,181]}],"children":[],"genes":[{"symbol":"SLC25A46","name":"solute carrier family 25 member 46","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"28637197[PMID]","hgnc":"25198","ensembl":"ENSG00000164209","omim":"610826","loci":["5q22.1"]},{"symbol":"AGTPBP1","name":"ATP/GTP binding carboxypeptidase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"30976113[PMID]","hgnc":"17258","ensembl":"ENSG00000135049","omim":"606830","loci":["9q21.33"]},{"symbol":"EXOSC3","name":"exosome component 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22544365[PMID]_25144110[PMID]","hgnc":"17944","ensembl":"ENSG00000107371","omim":"606489","loci":["9p13.2"]},{"symbol":"EXOSC8","name":"exosome component 8","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24989451[PMID]","hgnc":"17035","ensembl":"ENSG00000120699","omim":"606019","loci":["13q13.3"]},{"symbol":"EXOSC9","name":"exosome component 9","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"29727687[PMID]","hgnc":"9137","ensembl":"ENSG00000123737","omim":"606180","loci":["4q27"]},{"symbol":"VRK1","name":"VRK serine/threonine kinase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"19646678[PMID]","hgnc":"12718","ensembl":"ENSG00000100749","omim":"602168","loci":["14q32.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Family(ies)","class":null,"value":40.0,"area":"Worldwide","status":"Validated","source":"[EXPERT]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2022-09-16","source":"29656927[PMID]_35893425[PMID]_35852507[PMID]_24989451[PMID]","terms":[{"hpo":"HP:0007360","label":"Aplasia/Hypoplasia of the cerebellum","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002398","label":"Degeneration of anterior horn cells","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001265","label":"Hyporeflexia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003202","label":"Skeletal muscle atrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012110","label":"Hypoplasia of the pons","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000253","label":"Progressive microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000529","label":"Progressive visual loss","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002350","label":"Cerebellar cyst","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004886","label":"Congenital laryngeal stridor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003477","label":"Peripheral axonal neuropathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0033725","label":"Thin corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001308","label":"Tongue fasciculations","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002804","label":"Arthrogryposis multiplex congenita","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000565","label":"Esotropia","frequency":"Very rare (<4-1%)","criteria":null}]}}