{"orpha":3322,"name":"Hoyeraal-Hreidarsson syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Progressive pancytopenia-immunodeficiency-cerebellar hypoplasia syndrome"],"definition":"A rare X-linked syndromic intellectual disability considered to be a severe variant of dyskeratosis congenita characterized by intrauterine growth retardation, microcephaly, cerebellar hypoplasia, progressive combined immune deficiency and aplastic anemia.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-3322/","orphanet_url":"https://www.orpha.net/en/disease/detail/3322","names":{"fr":{"name":"Syndrome de Hoyeraal-Hreidarsson","synonyms":["Syndrome de pancytopénie progressive-déficit immunitaire-hypoplasie cérébelleuse"],"definition":"Déficience intellectuelle syndromique rare liée à l'X considérée comme une variante sévère de la dyskératose congénitale caractérisée par un retard de croissance intra-utérin, une microcéphalie, une hypoplasie cérébelleuse, un déficit immunitaire combiné progressif et une anémie aplasique."},"de":{"name":"Hoyeraal-Hreidarsson-Syndrom","synonyms":["Panzytopenie, progressive - Immundefekt - Kleinhirnhypoplasie"],"definition":"Eine seltene X-chromosomale syndromale Form der Intelligenzminderung, die als schwere Variante der Dyskeratosis congenita gilt und durch intrauterine Wachstumsverzögerung, Mikrozephalie, Kleinhirnhypoplasie, progressive kombinierte Immundefekte und aplastische Anämie gekennzeichnet ist."},"es":{"name":"Síndrome de Hoyeraal-Hreidarsson","synonyms":["Pancitopenia progresiva-inmunodeficiencia-hipoplasia cerebelosa"],"definition":"Es una discapacidad intelectual sindrómica poco frecuente ligada al cromosoma X considerada como una variante grave de la disqueratosis congénita y caracterizada por retraso del crecimiento intrauterino, microcefalia, hipoplasia cerebelosa, inmunodeficiencia combinada progresiva y anemia aplásica."},"it":{"name":"Sindrome di Hoyeraal-Hreidarsson","synonyms":["Pancitopenia progressiva - immunodeficienza - ipoplasia cerebellare"],"definition":"La sindrome di Hoyeraal-Hreidarsson (HHS) è una disabilità intellettiva sindromica legata all'X, ed è considerata la variante grave della discheratosi congenita. È caratterizzata da ritardo della crescita prenatale, microcefalia, ipoplasia cerebellare, immunodeficienza combinata progressiva ed anemia aplastica."},"nl":{"name":"Syndroom van Hoyeraal-Hreidarsson","synonyms":["Progressieve pancytopenie - immuundeficiëntie - cerebellaire hypoplasie-syndroom"],"definition":"Een zeldzame X-gebonden syndromale intellectuele achterstand die beschouwd wordt als een ernstige variant van dyskeratosis congenita, gekenmerkt door intra-uteriene groeiretardatie, microcefalie, cerebellaire hypoplasie, progressieve gecombineerde immuundeficiëntie, en aplastische anemie."},"pt":{"name":"Síndrome Hoyeraal-Hreidarsson","synonyms":["Síndrome de pancitopenia-imunodeficiência-hipoplasia cerebelosa"]},"pl":{"name":"Zespół Hoyeraala i Hreidarssona","synonyms":["Postępująca pancytopenia - Niedobór odporności - hipoplazja móżdżku"],"definition":"Rzadki zespół niepełnosprawności intelektualnej sprzężonej z chromosomem X, uważany za ciężki wariant wrodzonej dyskeratozy, charakteryzujący się opóźnieniem wzrostu wewnątrzmacicznego, małogłowiem, hipoplazją móżdżku, postępującym złożonym niedoborem odporności i niedokrwistością aplastyczną."},"cs":{"name":"Hoyeraalův-Hreidarssonův syndrom","synonyms":["Syndrom zahrnující progresivní pancytopenii, imunodeficienci a mozečkovou hypoplázii","Hoyeraal-Hreidarssonův syndrom"]},"uk":{"name":"Синдром Хойерала-Грейдарссона","synonyms":["Синдром прогресуючої панцитопенії-імунодефіциту-гіпоплазії мозочка"],"definition":"A rare X-linked syndromic intellectual disability considered to be a severe variant of dyskeratosis congenita characterized by intrauterine growth retardation, microcephaly, cerebellar hypoplasia, progressive combined immune deficiency and aplastic anemia."},"zh":{"name":"Hoyeraal-Hriedarsson综合征","synonyms":["进行性全血细胞减少-免疫缺陷-小脑发育不全综合征"]},"tr":{"name":"Hoyeraal-Hreidarsson sendromu","synonyms":["ilerleyici pansitopeni-immün yetmezlik-serebellar hipoplazi sendromu"]}},"xrefs":[{"source":"OMIM","code":"305000","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"OMIM","code":"613990","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614742","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614743","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"615190","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"616353","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"616553","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q82.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"3A70.0","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"340127408"},{"source":"MONDO","code":"0018045","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C536068","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1846142","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"346","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":97992,"name":"Rare hematologic disease"},"parents":[{"orpha":269567,"name":"Genetic syndrome with a cerebellar malformation as a major feature","classifications":[156]},{"orpha":728475,"name":"Inherited bone marrow failure disorder with immune defect","classifications":[156,195]},{"orpha":68383,"name":"Rare constitutional aplastic anemia","classifications":[156,194,233]},{"orpha":717877,"name":"Rare miscellaneous disease with inflammatory bowel disease","classifications":[152,156,233]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]},{"orpha":269523,"name":"Syndrome with a cerebellar malformation as a major feature","classifications":[147,181]},{"orpha":331217,"name":"Syndrome with combined immunodeficiency","classifications":[156,195]}],"children":[],"genes":[{"symbol":"ACD","name":"ACD shelterin complex subunit and telomerase recruitment factor","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"25233904[PMID]","hgnc":"25070","ensembl":"ENSG00000102977","omim":"609377","loci":["16q22.1"]},{"symbol":"DKC1","name":"dyskerin pseudouridine synthase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"33734615[PMID]","hgnc":"2890","ensembl":"ENSG00000130826","omim":"300126","loci":["Xq28"]},{"symbol":"PARN","name":"poly(A)-specific ribonuclease","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"25893599[PMID]","hgnc":"8609","ensembl":"ENSG00000140694","omim":"604212","loci":["16p13.12"]},{"symbol":"RTEL1","name":"regulator of telomere elongation helicase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23329068[PMID]_23453664[PMID]","hgnc":"15888","ensembl":"ENSG00000258366","omim":"608833","loci":["20q13.33"]},{"symbol":"TERC","name":"telomerase RNA component","gene_type":"Non-coding RNA","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"37037617[PMID]","hgnc":"11727","ensembl":"ENSG00000270141","omim":"602322","loci":["3q26.2"]},{"symbol":"TERT","name":"telomerase reverse transcriptase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"17785587[PMID]_23335200[PMID]","hgnc":"11730","ensembl":"ENSG00000164362","omim":"187270","loci":["5p15.33"]},{"symbol":"TINF2","name":"TERF1 interacting nuclear factor 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22078571[PMID]_21199492[PMID]_18669893[PMID]_20301779[PMID]","hgnc":"11824","ensembl":"ENSG00000092330","omim":"604319","loci":["14q12"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant","Autosomal recessive","X-linked recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"},{"type":"Cases/families","qualification":"Case(s)","class":null,"value":33.0,"area":"Worldwide","status":"Validated","source":"23453664[PMID]_23453664[PMID]_23329068[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004334","label":"Dermal atrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002721","label":"Immunodeficiency","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001873","label":"Thrombocytopenia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001928","label":"Abnormality of coagulation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001903","label":"Anemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007392","label":"Excessive wrinkled skin","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007440","label":"Generalized hyperpigmentation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011358","label":"Generalized hypopigmentation of hair","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008404","label":"Nail dystrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002745","label":"Oral leukoplakia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002216","label":"Premature graying of hair","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002209","label":"Sparse scalp hair","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001881","label":"Abnormal leukocyte morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005528","label":"Bone marrow hypocellularity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002514","label":"Cerebral calcification","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001265","label":"Hyporeflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002664","label":"Neoplasm","frequency":"Occasional (29-5%)","criteria":null}]}}