{"orpha":2268,"name":"ICF syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Immunodeficiency-centromeric instability-facial anomalies syndrome","Immunodeficiency-centromeric instability-facial dysmorphism syndrome"],"definition":"A rare autosomal recessive syndrome with combined immunodeficiency characterized by the clinical triad of immunodeficiency, centromeric instability and facial anomalies (abbreviated ICF syndrome). The immunodeficiency is with panhypogammaglobulinemia, and a lack of memory (CD19+CD27+) B cells in the peripheral blood, although B and T-cell counts are normal. Anomalies and rearrangements associated with DNA hypomethylation in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9, in mitogen-stimulated lymphocytes, is a hallmark of the syndrome. The typical facial anomalies include hypertelorism, low-set ears, epicanthus and macroglossia.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-2268/","orphanet_url":"https://www.orpha.net/en/disease/detail/2268","names":{"fr":{"name":"Syndrome ICF","synonyms":["Syndrome d'instabilité centromérique-immunodéficience-dysmorphie faciale","Syndrome d'instabilité de l'hétérochromatine paracentromérique-immunodéficience combinée-dysmorphie faciale"],"definition":"Syndrome autosomique récessif rare avec déficit immunitaire combiné caractérisé par la triade associant immunodéficience, instabilité centromérique et dysmorphie faciale (en abrégé syndrome ICF). Le déficit immunitaire se traduit par une panhypogammaglobulinémie et un manque de lymphocytes B mémoires (CD19+CD27+) dans le sang périphérique, bien que les numérations des lymphocytes B et T soient normales. Les anomalies et les réarrangements associés à l'hypométhylation de l'ADN à proximité des centromères (hétérochromatine juxtacentromérique) des chromosomes 1 et 16 et parfois 9, dans les lymphocytes stimulés par des mitogènes, sont caractéristiques du syndrome. La dysmorphie faciale caractéristique est à type d'hypertélorisme, d'oreilles d'implantation basse, d'épicanthus et de macroglossie."},"de":{"name":"ICF-Syndrom","synonyms":["Immunodefizienz-Zentromerinstabilität-faziale Anomalien-Syndrom"],"definition":"Ein seltenes autosomal-rezessives Syndrom mit kombiniertem Immundefekt, das durch die klinische Trias von Immundefizienz, Zentromer-Instabilität und Gesichtsanomalien gekennzeichnet ist (abgekürzt ICF-Syndrom). Der Immundefekt geht mit einer Panhypogammaglobulinämie und einem Mangel an B-Gedächtniszellen (CD19+CD27+) im peripheren Blut einher, obwohl die Anzahl der B- und T-Zellen normal ist. Anomalien und Umlagerungen in Verbindung mit einer DNA-Hypomethylierung in der Nähe der Zentromere (dem juxtazentromerischen Heterochromatin) der Chromosomen 1 und 16 und manchmal 9 in mitogen stimulierten Lymphozyten sind ein Markenzeichen des Syndroms. Zu den typischen Gesichtsanomalien gehören Hypertelorismus, tief angesetzte Ohren, Epikanthus und Makroglossie."},"es":{"name":"Síndrome ICF","synonyms":["Síndrome de inmunodeficiencia-inestabilidad centromérica-anomalías faciales","Síndrome de inmunodeficiencia-inestabilidad centromérica-dismorfia facial"],"definition":"Es un síndrome autosómico recesivo poco frecuente con inmunodeficiencia combinada caracterizado por la tríada clínica de inmunodeficiencia, inestabilidad centromérica y anomalías faciales (síndrome ICF, por sus siglas en inglés). La inmunodeficiencia se presenta con panhipogammaglobulinemia y linfopenia de células B de memoria (CD19+CD27+) en sangre periférica, aunque los recuentos de células B y T son normales. Las anomalías y reordenamientos asociados a hipometilación del ADN en la proximidad de los centrómeros (heterocromatina yuxtacentromérica) de los cromosomas 1 y 16 y, en ocasiones, del 9, en linfocitos estimulados por mitógenos, son un sello distintivo del síndrome. Las anomalías faciales típicas incluyen hipertelorismo, orejas de implantación baja, epicanto y macroglosia."},"it":{"name":"Sindrome ICF","synonyms":["Instabilità centromerica - immunodeficienza - dismorfismi","Sindrome immunodeficienza-instabilità centromerica-anomalie facciali","Sindrome immunodeficienza-instabilità centromerica-dismorfismi facciali"]},"nl":{"name":"ICF-syndroom","synonyms":["Immuundeficiëntie - centromeerinstabiliteit - faciale anomalieën-syndroom","Immuundeficiëntie - centromeerinstabiliteit - faciale dysmorfie-syndroom"],"definition":"Een zeldzaam autosomaal recessief syndroom met gecombineerde immuundeficiëntie, gekenmerkt door de klinische triade van immuundeficiëntie, centromeerinstabiliteit en faciale anomalieën (afgekort als ICF-syndroom). De immuundeficiëntie omvat panhypogammaglobulinemie en gebrek aan B-geheugencellen (CD19+CD27+) in perifeer bloed, hoewel het aantal B- en T-cellen normaal is. Anomalieën en herschikkingen geassocieerd met DNA-hypomethylatie nabij de centromeren (juxtacentromeer heterochromatine) van chromosomen 1 en 16, en soms 9, in mitogeen-gestimuleerde lymfocyten is een typisch kenmerk van het syndroom. De typische gelaatsanomalieën zijn hypertelorisme, laagstaande oren, epicanthus en macroglossie."},"pt":{"name":"Síndrome ICF","synonyms":["Síndrome de imunodeficiência-instabilidade centromérica-anomalias faciais","Síndrome de imunodeficiência-instabilidade centromérica-dismorfia facial","Síndrome de instabilidade centromérica-imunodeficiência"],"definition":"Síndrome autossómica recessiva rara com imunodeficiência combinada caracterizada pela tríade clínica de imunodeficiência, instabilidade centromérica e anomalias faciais (abreviada síndrome ICF). A imunodeficiência é com pan-hipogamaglobulinemia e uma falta de células B de memória (CD19+CD27+) no sangue periférico, embora as contagens de células B e T sejam normais. Anomalias e rearranjos associados à hipometilação do DNA na vizinhança dos centrómeros (a heterocromatina justacentromérica) dos cromossomas 1 e 16 e às vezes 9, em linfócitos estimulados por mitógenos, são uma característica da síndrome. As anomalias faciais típicas incluem hipertelorismo, orelhas de implantação baixa, epicanto e macroglossia."},"pl":{"name":"Zespół ICF","synonyms":["Niedobór odporności - niestabilność centromeryczna - anomalie twarzy"]},"cs":{"name":"ICF syndrom","synonyms":["Imunodeficience spojená s centromerickou nestabilitou a faciálním dysmorfismem","ICF"]},"uk":{"name":"Синдром ICF","synonyms":["Синдром імунодефіциту-центромерної нестабільності-лицьових аномалій","Синдром імунодефіциту-центромерної нестабільності-лицевого дисморфізму"],"definition":"A rare autosomal recessive syndrome with combined immunodeficiency characterized by the clinical triad of immunodeficiency, centromeric instability and facial anomalies (abbreviated ICF syndrome). The immunodeficiency is with panhypogammaglobulinemia, and a lack of memory (CD19+CD27+) B cells in the peripheral blood, although B and T-cell counts are normal. Anomalies and rearrangements associated with DNA hypomethylation in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9, in mitogen-stimulated lymphocytes, is a hallmark of the syndrome. The typical facial anomalies include hypertelorism, low-set ears, epicanthus and macroglossia."},"zh":{"name":"ICF综合征","synonyms":["免疫缺陷-着丝粒不稳定-面部异常综合征"]},"tr":{"name":"ICF sendromu","synonyms":["İmmün yetmezlik-sentromerik instabilite-fasiyal anomalileri sendromu"]}},"xrefs":[{"source":"OMIM","code":"242860","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614069","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"616910","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"616911","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"D84.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"4A01.00","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1446083793"},{"source":"MONDO","code":"0000133","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0398788","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"2945","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98004,"name":"Rare immune disease"},"parents":[{"orpha":169346,"name":"DNA repair defect other than combined T-cell and B-cell immunodeficiencies","classifications":[156,195,233]},{"orpha":717757,"name":"Rare immune 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]}],"children":[],"genes":[{"symbol":"CDCA7","name":"cell division cycle associated 7","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"26216346[PMID]","hgnc":"14628","ensembl":"ENSG00000144354","omim":"609937","loci":["2q31.1"]},{"symbol":"DNMT3B","name":"DNA methyltransferase 3 beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"10588719[PMID]","hgnc":"2979","ensembl":"ENSG00000088305","omim":"602900","loci":["20q11.21"]},{"symbol":"HELLS","name":"helicase, lymphoid specific","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"26216346[PMID]","hgnc":"4861","ensembl":"ENSG00000119969","omim":"603946","loci":["10q23.33"]},{"symbol":"UHRF1","name":"ubiquitin like with PHD and ring finger domains 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"36458887[PMID]","hgnc":"12556","ensembl":"ENSG00000276043","omim":"607990","loci":["19p13.3"]},{"symbol":"ZBTB24","name":"zinc finger and BTB domain containing 24","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21906047[PMID]","hgnc":"21143","ensembl":"ENSG00000112365","omim":"614064","loci":["6q21"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Childhood"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":66.0,"area":"Worldwide","status":"Validated","source":"23486536[PMID]"},{"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":"2016-06-01","source":null,"terms":[{"hpo":"HP:0003220","label":"Abnormality of chromosome stability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004313","label":"Decreased circulating antibody level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002721","label":"Immunodeficiency","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002205","label":"Recurrent respiratory infections","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001874","label":"Abnormality of neutrophils","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001903","label":"Anemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005374","label":"Cellular immunodeficiency","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001334","label":"Communicating hydrocephalus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005280","label":"Depressed nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001888","label":"Lymphopenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000256","label":"Macrocephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002024","label":"Malabsorption","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012368","label":"Flat face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000158","label":"Macroglossia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010808","label":"Protruding tongue","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001537","label":"Umbilical hernia","frequency":"Occasional (29-5%)","criteria":null}]}}