{"orpha":221139,"name":"Combined immunodeficiency with facio-oculo-skeletal anomalies","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Roifman-Chitayat syndrome"],"definition":"A rare combined immunodeficiency disorder characterized by primary immunodeficiency manifesting with repeated bacterial, viral and fungal infections, in association with neurological manifestations (hypotonia, cerebellar ataxia, myoclonic seizures), developmental delay, optic atrophy, facial dysmorphism (high forehead, hypoplastic supraorbital ridges, palpebral edema, hypertelorism, flat nasal bridge, broad nasal root and tip, anteverted nares, thin lower lip overlapped by upper lip, square chin) and skeletal anomalies (short metacarpals/metatarsals with cone-shaped epiphyses, osteopenia).","note":null,"url":"https://raremap.alftech.space/d/ORPHA-221139/","orphanet_url":"https://www.orpha.net/en/disease/detail/221139","names":{"fr":{"name":"Déficit immunitaire combiné avec anomalies facio-oculo-squelettiques","synonyms":["Syndrome de Roifman-Chitayat"],"definition":"Un syndrome d'immunodéficience combinée extrêmement rare caractérisé par une immunodéficience primaire se manifestant par des infections bactériennes, virales et fongiques répétées, associées à des manifestations neurologiques (hypotonie, ataxie cérébelleuse, convulsions myocloniques), un retard de développement, une atrophie optique, une dysmorphie faciale (front haut, crêtes supraorbitales hypoplasiques, oedème palpébral, hypertélorisme, pont nasal plat, racine et pointe nasales larges, narines antéversées, lèvre inférieure fine superposée par la lèvre supérieure, menton de forme carrée) et des anomalies squelettiques (métacarpes/métatarses courts avec des épiphyses coniques, ostéopénie)."},"de":{"name":"Kombinierter Immundefekt mit fazio-okulo-skelettalen Anomalien","synonyms":["Roifman-Chitayat-Syndrom"],"definition":"Eine seltene Immunstörung, die durch einen primären kombinierten Immundefekt mit wiederholten bakteriellen, viralen und Pilzinfektionen gekennzeichnet ist. Zu den charakteristischen Merkmale gehören neurologischen Manifestationen (Hypotonie, zerebelläre Ataxie, myoklonische Anfälle), Entwicklungsverzögerung, Optikusatrophie, Gesichtsdysmorphien (hohe Stirn, hypoplastische Augenlider, Lidödem, Hypertelorismus), antevertierte Nasenlöcher, dünne Unterlippe, die von der Oberlippe überlappt wird, quadratisches Kinn) und Skelettanomalien (kurze Metakarpophalangeal-/Metatarsalknochen mit konischen Epiphysen, Osteopenie)."},"es":{"name":"Inmunodeficiencia combinada con anomalías facio-óculo-esqueléticas","synonyms":["Síndrome de Roifman-Chitayat"],"definition":"Es una inmunodeficiencia combinada muy poco frecuente caracterizada por inmunodeficiencia primaria que se manifiesta con infecciones bacterianas, virales y fúngicas recurrentes, asociada a manifestaciones neurológicas (hipotonía, ataxia cerebelosa, convulsiones mioclónicas), retraso en el desarrollo, atrofia óptica, atrofia facial, dismorfia facial (frente alta, crestas supraorbitales hipoplásicas, edema palpebral, hipertelorismo, puente nasal plano, raíz y punta nasales anchas, narinas antevertidas, labio superior solapando al labio inferior que es delgado, mentón cuadrado) y anomalías esqueléticas (metacarpianos / metatarsianos cortos con epífisis cónicas, osteopenia)."},"it":{"name":"Immunodeficienza combinata con anomalie facio-oculo-scheletriche","synonyms":["Sindrome di Roifman-Chitayat"],"definition":"L'immunodeficienza combinata con anomalie facio-oculo-scheletriche è un'immunodeficienza combinata molto rara, caratterizzata da immunodeficienza primitiva, che esordisce con infezioni batteriche, virali e fungine recidivanti, associate a sintomi neurologici (ipotonia, atassia cerebellare, crisi miocloniche), ritardo dello sviluppo, atrofia ottica, dismorfismi facciali (fronte alta, arcate sopraorbitali ipoplastiche, edema palpebrale, ipertelorismo, sella nasale piatta, radice e punta nel naso ampie, narici anteverse, labbro inferiore sottile con sovrapposizione del labbro superiore, mento squadrato) e anomalie scheletriche (metacarpi/metatarsi corti con epifisi a cono, osteopenia)."},"nl":{"name":"Gecombineerde immuundeficiëntie met facio-oculoskeletale anomalieën","synonyms":["Syndroom van Roifman-Chitayat"],"definition":"Een zeldzame gecombineerde immuundeficiëntie, gekenmerkt door primaire immuundeficiëntie die zich manifesteert met recidiverende bacteriële, virale en fungale infecties, in associatie met neurologische manifestaties (hypotonie, cerebellaire ataxie, myoclonische insulten), ontwikkelingsachterstand, opticusatrofie, faciale dysmorfie (hoog voorhoofd, hypoplastische supraorbitale randen, oedeem van ooglid, hypertelorisme, platte neusbrug, brede neuswortel en neuspunt, anteversie van neusgaten, dunne onderlip met overlappende bovenlip, vierkante kin) en skeletanomalieën (korte metacarpalen/metatarsalen met kegelvormige epifysen, osteopenie)."},"pt":{"name":"Imunodeficiência combinada com anomalias facio-oculo-esqueléticas"},"pl":{"name":"Złożony niedobór odporności z anomaliami twarzowo-oczno-szkieletowymi","synonyms":["Zespół Roifmana i Chitayat"],"definition":"*Złożony niedobór odporności z wadami twarzowo-oczno-szkieletowymi jest niezwykle rzadkim, złożonym zespołem z niedoborem odporności, który charakteryzuje się pierwotnym niedoborem odporności z nawracającymi zakażeniami bakteryjnymi, wirusowymi i grzybiczymi, z towarzyszącymi objawami neurologicznymi (hipotonia, ataksja móżdżkowa, drgawki miokloniczne), opóźnieniem rozwoju, zanikiem nerwu wzrokowego, dysmorfią twarzy (wysokie czoło, hipoplastyczne krawędzie nadoczodołowe, obrzęk powiek, hiperteloryzm, płaski grzbiet nosa, szeroka nasada i czubek nosa, odwrócone nozdrza, wąska dolna warga z zachodzącą na nią górną wargą, kwadratowy podbródek) i wadami szkieletowymi (krótkie śródręcza/śródstopia z nasadami w kształcie stożka, osteopenia)."},"cs":{"name":"Kombinovaná imunodeficience s facio-okulo-skeletálními anomáliemi","synonyms":["Roifmanův-Chitayatův syndrom","Roifman-Chitayatův syndrom"]},"uk":{"name":"Комбінований імунодефіцит з лицьово-окуло-скелетними аномаліями","synonyms":["Синдром Ройфмана-Чітаята"],"definition":"A rare combined immunodeficiency disorder characterized by primary immunodeficiency manifesting with repeated bacterial, viral and fungal infections, in association with neurological manifestations (hypotonia, cerebellar ataxia, myoclonic seizures), developmental delay, optic atrophy, facial dysmorphism (high forehead, hypoplastic supraorbital ridges, palpebral edema, hypertelorism, flat nasal bridge, broad nasal root and tip, anteverted nares, thin lower lip overlapped by upper lip, square chin) and skeletal anomalies (short metacarpals/metatarsals with cone-shaped epiphyses, osteopenia)."},"zh":{"name":"联合免疫缺陷伴面-眼-骨骼异常","synonyms":["Roifman-Chitayat综合征"],"definition":"联合免疫缺陷伴面颈部畸形是一种极罕见的联合免疫缺陷疾病，其特征是原发性免疫缺陷，表现为反复的细菌、病毒和真菌感染，并伴有神经系统症状（肌张力低下、小脑共济失调、肌阵挛发作）、发育迟缓，视神经萎缩、面部畸形（高额头、眶上嵴发育不全、眼睑水肿、斜视、鼻梁扁平、鼻根和鼻尖较宽、鼻孔前倾、下唇薄并与上唇交叠，方下巴），骨骼异常（掌骨/跖骨短，骨骺呈锥形，骨量减少）。"},"tr":{"name":"Fasiyo-okülo-iskelet anomalileri ile seyreden kombine immün yetmezlik","synonyms":["Roifman-Chitayat sendromu"]}},"xrefs":[{"source":"OMIM","code":"613328","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"4A01.1Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"233206593"},{"source":"MONDO","code":"0013226","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C567641","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C2750068","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":404574,"name":"Genetic syndrome with limb reduction defects","classifications":[156]},{"orpha":169349,"name":"Immuno-osseous dysplasia","classifications":[156,195]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":506219,"name":"Rare disorder potentially indicated for hematopoietic stem cell transplant","classifications":[233]},{"orpha":294955,"name":"Syndrome with limb reduction defects","classifications":[147,199]}],"children":[],"genes":[{"symbol":"KNSTRN","name":"kinetochore localized astrin (SPAG5) binding protein","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"29180244[PMID]","hgnc":"30767","ensembl":"ENSG00000128944","omim":"614718","loci":["15q15.1"]},{"symbol":"PIK3CD","name":"phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"29180244[PMID]","hgnc":"8977","ensembl":"ENSG00000171608","omim":"602839","loci":["1p36.22"]}],"genes_via_subtypes":[],"inheritance":["Multigenic/multifactorial"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":2.0,"area":"Worldwide","status":"Validated","source":"19863561[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_19863561[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-06-17","source":"29180244[PMID]_19863561[PMID]","terms":[{"hpo":"HP:0025540","label":"Abnormal T cell subset distribution","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000306","label":"Abnormality of the chin","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000924","label":"Abnormality of the skeletal system","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031014","label":"Arteria lusoria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001369","label":"Arthritis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009844","label":"Broad middle phalanx of finger","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000455","label":"Broad nasal tip","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009098","label":"Chronic oral candidiasis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040022","label":"Clinodactyly of the 2nd finger","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040024","label":"Clinodactyly of the 3rd finger","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040025","label":"Clinodactyly of the 4th finger","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005387","label":"Combined immunodeficiency","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010579","label":"Cone-shaped epiphysis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004313","label":"Decreased circulating antibody level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003460","label":"Decreased circulating total IgA","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0032132","label":"Decreased circulating total IgG","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002850","label":"Decreased circulating total IgM","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031382","label":"Decreased lymphocyte proliferation in response to anti-CD3","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031381","label":"Decreased lymphocyte proliferation in response to mitogen","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0032218","label":"Decreased proportion of CD4-positive T cells","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0032140","label":"Decreased specific antibody response to vaccination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010976","label":"Decreased total B cell count","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000490","label":"Deeply set eye","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005280","label":"Depressed nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010750","label":"Dermatochalasis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002123","label":"Generalized myoclonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000348","label":"High forehead","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003307","label":"Hyperlordosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000953","label":"Hyperpigmentation of the skin","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000998","label":"Hypertrichosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002080","label":"Intention tremor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007678","label":"Lacrimal duct stenosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002162","label":"Low posterior hairline","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002058","label":"Myopathic facies","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040288","label":"Nasogastric tube feeding","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001319","label":"Neonatal hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002643","label":"Neonatal respiratory distress","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000609","label":"Optic nerve hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000938","label":"Osteopenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100540","label":"Palpebral edema","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001761","label":"Pes cavus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002403","label":"Positive Romberg sign","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000411","label":"Protruding ear","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003765","label":"Psoriasiform dermatitis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002100","label":"Recurrent aspiration pneumonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002718","label":"Recurrent bacterial infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0410018","label":"Recurrent ear infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002841","label":"Recurrent fungal infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000010","label":"Recurrent urinary tract infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004429","label":"Recurrent viral infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040218","label":"Reduced natural killer cell count","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009650","label":"Short distal phalanx of the thumb","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010282","label":"Thin lower lip vermilion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001537","label":"Umbilical hernia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009891","label":"Underdeveloped supraorbital ridges","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000122","label":"Unilateral renal agenesis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006610","label":"Wide intermamillary distance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002014","label":"Diarrhea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004425","label":"Flat forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002007","label":"Frontal bossing","frequency":"Occasional (29-5%)","criteria":null}]}}