{"orpha":3301,"name":"Tetraamelia-multiple malformations syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["PAPPA syndrome","PAPPAS","Zimmer phocomelia"],"definition":"An extremely rare mostly lethal congenital disorder characterized by absence of all four limbs and frequent associated major malformations involving the head, face, eyes, skeleton, heart, lungs, anus, urogenital, and central nervous systems. The syndrome has been described in fewer than 20 patients mainly of middle Eastern descent.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-3301/","orphanet_url":"https://www.orpha.net/en/disease/detail/3301","names":{"fr":{"name":"Syndrome de tetra-amélie-malformations multiples","synonyms":["PAPPAS","Phocomélie de Zimmer","Syndrome PAPPA"],"definition":"Maladie congénitale extrêmement rare, généralement létale, caractérisée par l'absence des quatre membres et de fréquentes malformations majeures associées affectant la tête, le visage, les yeux, le squelette, le coeur, les poumons, l'anus, le système urogénital et le système nerveux central. Le syndrome a été décrit chez moins de vingt patients, principalement originaire du Moyen-Orient."},"de":{"name":"Syndrom der Tetraamelie mit multiplen Fehlbildungen","synonyms":["PAPPA-Syndrom","PAPPAS","PAPPAS-Syndrom","Zimmer-Phokomelie"],"definition":"Eine äußerst seltene, meist letale angeborene Störung, die durch das Fehlen aller vier Gliedmaßen gekennzeichnet ist und häufig mit schweren Fehlbildungen von Kopf, Gesicht, Augen, Skelett, Herz, Lunge, Anus, Urogenitaltrakt und zentralem Nervensystem einhergeht. Das Syndrom wurde bei weniger als 20 Patienten, hauptsächlich mit nahöstlicher Abstammung, beschrieben."},"es":{"name":"Síndrome de tetraamelia-malformaciones múltiples","synonyms":["Focomelia de Zimmer","PAPPAS","Síndrome PAPPA"],"definition":"Es un trastorno congénito muy poco frecuente, generalmente letal, que se caracteriza por la ausencia de las cuatro extremidades y que está con frecuencia asociado a malformaciones mayores que afectan a cabeza, cara, ojos, esqueleto, corazón, pulmones, ano, y a los sistemas urogenital y nervioso central. El síndrome ha sido descrito en menos de 20 pacientes, principalmente con origen en Oriente Medio."},"it":{"name":"Sindrome tetra-amelia-malformazioni multiple","synonyms":["Sindrome di PAPPA","PAPPAS","Focomelia di Zimmer"],"definition":"La tetraamelia - malformazioni multiple è un difetto congenito estremamente raro, per lo più letale, caratterizzato dall'assenza dei quattro arti e, spesso, significative malformazioni correlate, che interessano la testa, la faccia, gli occhi, lo scheletro, il cuore, i polmoni, l'ano, l'apparato urogenitale e il sistema nervoso centrale. La sindrome è stata descritta in meno di 20 pazienti, in particolare originari del Medio Oriente."},"nl":{"name":"Tetra-amelie - multipele malformaties-syndroom","synonyms":["Focomelie van Zimmer","PAPPA-syndroom","PAPPAS"],"definition":"Een uiterst zeldzame, meestal letale congenitale aandoening, gekenmerkt door afwezigheid van alle vier de ledematen, en vaak associatie van ernstige malformaties met betrokkenheid van hoofd, gelaat, ogen, skelet, hart, longen, anus, urogenitaal stelsel, en centraal zenuwstelsel. Het syndroom werd beschreven bij minder dan 20 patiënten, vooral van Midden-Oosterse afkomst."},"pt":{"name":"Síndrome de tetra-amelia-malformações múltiplas","synonyms":["Focomelia Zimmer","PAPPAS","Síndrome PAPPA"]},"pl":{"name":"Tetraamelia - mnogie malformacje","synonyms":["Fokomelia Zimmera"]},"cs":{"name":"Syndrom zahrnující tetraamelii a mnohočetné malformace","synonyms":["Zimmerova fokomelie"]},"uk":{"name":"Синдром тетраамелії - множинних вад розвитку","synonyms":["Фокомелія Циммера"],"definition":"An extremely rare mostly lethal congenital disorder characterized by absence of all four limbs and frequent associated major malformations involving the head, face, eyes, skeleton, heart, lungs, anus, urogenital, and central nervous systems. The syndrome has been described in fewer than 20 patients mainly of middle Eastern descent."},"zh":{"name":"无四肢-多发畸形综合征","synonyms":["Zimmer短肢畸形"]},"tr":{"name":"Tetraamelia-çoklu malformasyon sendromu","synonyms":["Zimmer fokomeli"]}},"xrefs":[{"source":"OMIM","code":"273395","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"601360","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618021","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD2F.1Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1919082958"},{"source":"MONDO","code":"0010110","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C536500","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C2931218","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"386","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[{"type":"Moved to","orpha":1027,"name":"Autosomal recessive amelia","status":"inactive"}],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":330206,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual disability","classifications":[156]},{"orpha":404574,"name":"Genetic syndrome with limb reduction defects","classifications":[156]},{"orpha":102285,"name":"Multiple congenital anomalies/dysmorphic syndrome without intellectual disability","classifications":[147]},{"orpha":294955,"name":"Syndrome with limb reduction defects","classifications":[147,199]},{"orpha":98641,"name":"Syndromic cataract","classifications":[189]},{"orpha":522548,"name":"Syndromic genetic cataract","classifications":[156]}],"children":[],"genes":[{"symbol":"WNT3","name":"Wnt family member 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"14872406[PMID]_20301453[PMID]","hgnc":"12782","ensembl":"ENSG00000108379","omim":"165330","loci":["17q21.31-q21.32"]},{"symbol":"RSPO2","name":"R-spondin 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"29769720[PMID]","hgnc":"28583","ensembl":"ENSG00000147655","omim":"610575","loci":["8q23.1"]},{"symbol":"TBX4","name":"T-box transcription factor 4","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"31965066[PMID]","hgnc":"11603","ensembl":"ENSG00000121075","omim":"601719","loci":["17q23.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive","X-linked recessive"],"onset":["Antenatal","Infancy","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_20301453[PMID]"},{"type":"Cases/families","qualification":"Family(ies)","class":null,"value":5.0,"area":"Worldwide","status":"Validated","source":"20301453[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2024-07-18","source":"7625439[PMID]_4076260[PMID]_31761294[PMID]","terms":[{"hpo":"HP:0009924","label":"Aplasia/Hypoplasia involving the nose","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0009103","label":"Aplasia/Hypoplasia involving the pelvis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0006703","label":"Aplasia/Hypoplasia of the lungs","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000238","label":"Hydrocephalus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008551","label":"Microtia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000202","label":"Orofacial cleft","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001561","label":"Polyhydramnios","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003057","label":"Tetraamelia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001671","label":"Abnormal cardiac septum morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002101","label":"Abnormal lung lobation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000772","label":"Abnormal rib morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001600","label":"Abnormality of the larynx","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100569","label":"Abnormally ossified vertebrae","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010494","label":"Acromelia of the lower limbs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001274","label":"Agenesis of corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009812","label":"Amelia involving the upper limbs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002023","label":"Anal atresia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006709","label":"Aplasia/Hypoplasia of the nipples","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000293","label":"Full cheeks","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008736","label":"Hypoplasia of penis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000612","label":"Iris coloboma","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000482","label":"Microcornea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000568","label":"Microphthalmia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000921","label":"Missing ribs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000003","label":"Multicystic kidney dysplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000160","label":"Narrow mouth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100335","label":"Non-midline cleft of the upper lip","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100842","label":"Septo-optic dysplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000046","label":"Small scrotum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002777","label":"Tracheal stenosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000148","label":"Vaginal atresia","frequency":"Frequent (79-30%)","criteria":null}]}}