{"orpha":648,"name":"Noonan syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare, highly variable, multisystemic disorder mainly characterized by short stature, distinctive facial features, congenital heart defects, cardiomyopathy and an increased risk to develop tumors in childhood.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-648/","orphanet_url":"https://www.orpha.net/en/disease/detail/648","names":{"fr":{"name":"Syndrome de Noonan","definition":"Maladie rare, très variable et multisystémique, principalement caractérisée par une petite taille, une dysmorphie faciale caractéristique, des anomalies cardiaques congénitales, une cardiomyopathie et un risque accru de développer des tumeurs pendant l'enfance."},"de":{"name":"Noonan-Syndrom","definition":"Eine seltene, hochvariable, multisystemische Erkrankung, die gekennzeichnet ist durch Kleinwuchs, typische faziale Dysmorphien, angeborene Herzfehler, Kardiomyopathie und ein erhöhtes Risiko, im Kindesalter Tumore zu entwickeln."},"es":{"name":"Síndrome de Noonan","definition":"Es un trastorno multisistémico poco frecuente, altamente variable, caracterizado principalmente por talla baja, rasgos faciales distintivos, cardiopatías congénitas, miocardiopatía y un mayor riesgo de desarrollar tumores en la infancia."},"it":{"name":"Sindrome di Noonan","definition":"La sindrome di Noonan (SN) è una malattia multisistemica rara molto variabile, caratterizzata prevalentemente da bassa statura, dismorfismi facciali caratteristici, cardiopatie congenite, cardiomiopatia e rischio aumentato di sviluppare tumori durante l'infanzia. Di solito la malattia esordisce nel periodo neonatale con difficoltà di alimentazione e ritardo della crescita. Spesso i dismorfismi facciali caratteristici sono maggiormente evidenti nell'infanzia: fronte alta e ampia, ipertelorismo, ptosi palpebrale e rime palpebrali oblique verso il basso, orecchie spesse a impianto basso e ruotate posteriormente, filtro profondo, micrognazia, capelli ricci e collo corto, talvolta con pterigio. Con l'età, il viso diventa triangolare, con pliche cutanee marcate. La cardiopatia congenita più comune è la stenosi della valvola polmonare (50-60%) con displasia della valvola polmonare e diverse malformazioni cardiache (difetti del setto interatriale e interventricolare, ecc.). È comune la cardiomiopatia ipertrofica ad esordio prenatale (20%), che può essere stabile o a progressione rapida. Con l'invecchiamento i pazienti possono sviluppare una dilatazione delle arterie coronarie e la malattia moyamoya."},"nl":{"name":"Syndroom van Noonan","definition":"Een zeldzame, zeer variabele, multisystemische aandoening, vooral gekarakteriseerd door kleine gestalte, typische gelaatskenmerken, congenitale hartdefecten, cardiomyopathie en een verhoogd risico op ontwikkeling van tumoren in de kindertijd."},"pt":{"name":"Síndrome Noonan","synonyms":["Síndrome pseudo-Turner"],"definition":"A síndrome de Noonan (NS) é caracterizada por baixa estatura, dismorfismos faciais típicos e defeitos cardíacos congénitos."},"pl":{"name":"Zespół Noonan","definition":"Rzadka, wieloukładowa choroba o dużej zmienności, charakteryzująca się głównie niskim wzrostem, typowymi rysami twarzy, wrodzonymi wadami serca, kardiomiopatią i zwiększonym ryzykiem rozwoju nowotworów w dzieciństwie."},"cs":{"name":"Syndrom Noonanové"},"uk":{"name":"Синдром Нунана","definition":"A rare, highly variable, multisystemic disorder mainly characterized by short stature, distinctive facial features, congenital heart defects, cardiomyopathy and an increased risk to develop tumors in childhood."},"zh":{"name":"Noonan综合征"},"tr":{"name":"Noonan sendromu"}},"xrefs":[{"source":"OMIM","code":"163950","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"605275","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"609942","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"610733","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"611553","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"613224","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"613706","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"615355","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"616559","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"616564","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618499","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618624","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"619087","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"619745","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.1","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"LD2F.15","qualifier":"E","icd_relation":"specific","validated":true,"icd11_uri":"1044395354"},{"source":"MONDO","code":"0018997","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D009634","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0028326","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"10955","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10029748","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":568047,"name":"Disorder with multisystemic involvement and primary lymphedema","classifications":[147,156,187,198]},{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":619340,"name":"Inherited hematologic cancer-predisposing syndrome","classifications":[156,202]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":98733,"name":"Noonan syndrome and Noonan-related syndrome","classifications":[147,148,156]},{"orpha":183422,"name":"Polymalformative genetic syndrome with increased risk of developing cancer","classifications":[156,202]},{"orpha":477771,"name":"Rare disorder with a moyamoya angiopathy","classifications":[156,181]},{"orpha":181441,"name":"Rare disorder with hypergonadotropic hypogonadism","classifications":[156,193,201]},{"orpha":98578,"name":"Rare disorder with ptosis","classifications":[147,156,189]},{"orpha":217595,"name":"Syndrome associated with hypertrophic cardiomyopathy","classifications":[146,156,233]},{"orpha":139393,"name":"Syndromic craniosynostosis","classifications":[147,156,199]},{"orpha":98576,"name":"Syndromic outer canthal malposition","classifications":[147,156,189]},{"orpha":93547,"name":"Syndromic renal or urinary tract malformation","classifications":[147,156,188,233]}],"children":[],"genes":[{"symbol":"RRAS","name":"RAS related","gene_type":"gene with protein product","association":"Candidate gene tested in","status":"Not yet assessed","source":"24705357[PMID]","hgnc":"10447","ensembl":"ENSG00000126458","omim":"165090","loci":["19q13.33"]},{"symbol":"RAF1","name":"Raf-1 proto-oncogene, serine/threonine kinase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (gain of function) 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in","status":"Assessed","source":"25049390[PMID]","hgnc":"9872","ensembl":"ENSG00000155903","omim":"601589","loci":["3q23"]},{"symbol":"BRAF","name":"B-Raf proto-oncogene, serine/threonine kinase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"19206169[PMID]","hgnc":"1097","ensembl":"ENSG00000157764","omim":"164757","loci":["7q34"]},{"symbol":"CBL","name":"Cbl proto-oncogene","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"25952305[PMID]","hgnc":"1541","ensembl":"ENSG00000110395","omim":"165360","loci":["11q23.3"]},{"symbol":"KRAS","name":"KRAS proto-oncogene, GTPase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"16773572[PMID]","hgnc":"6407","ensembl":"ENSG00000133703","omim":"190070","loci":["12p12.1"]},{"symbol":"LZTR1","name":"leucine zipper like post translational regulator 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"25795793[PMID]","hgnc":"6742","ensembl":"ENSG00000099949","omim":"600574","loci":["22q11.21"]},{"symbol":"MRAS","name":"muscle RAS oncogene homolog","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"28289718[PMID]","hgnc":"7227","ensembl":"ENSG00000158186","omim":"608435","loci":["3q22.3"]},{"symbol":"NRAS","name":"NRAS proto-oncogene, GTPase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"19966803[PMID]","hgnc":"7989","ensembl":"ENSG00000213281","omim":"164790","loci":["1p13.2"]},{"symbol":"PTPN11","name":"protein tyrosine phosphatase non-receptor type 11","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"19760651[PMID]","hgnc":"9644","ensembl":"ENSG00000179295","omim":"176876","loci":["12q24.13"]},{"symbol":"RRAS2","name":"RAS related 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"31130285[PMID]","hgnc":"17271","ensembl":"ENSG00000133818","omim":"600098","loci":["11p15.2"]},{"symbol":"SOS2","name":"SOS Ras/Rho guanine nucleotide exchange factor 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"25795793[PMID]","hgnc":"11188","ensembl":"ENSG00000100485","omim":"601247","loci":["14q21.3"]},{"symbol":"SPRED2","name":"sprouty related EVH1 domain containing 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) 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(99-80%)","criteria":null},{"hpo":"HP:0000044","label":"Hypogonadotropic hypogonadism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011800","label":"Midface retrusion","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000768","label":"Pectus carinatum","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000767","label":"Pectus excavatum","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000520","label":"Proptosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004415","label":"Pulmonary artery stenosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000179","label":"Thick lower lip vermilion","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000391","label":"Thickened helices","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000474","label":"Thickened nuchal skin fold","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000325","label":"Triangular face","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000465","label":"Webbed neck","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0006610","label":"Wide intermamillary distance","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001892","label":"Abnormal bleeding","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007477","label":"Abnormal dermatoglyphics","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011362","label":"Abnormal hair quantity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011869","label":"Abnormal platelet function","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001641","label":"Abnormal pulmonary valve morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001928","label":"Abnormality of coagulation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000078","label":"Abnormality of the genital system","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100763","label":"Abnormality of the lymphatic system","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001743","label":"Abnormality of the spleen","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011675","label":"Arrhythmia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000635","label":"Blue irides","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002208","label":"Coarse hair","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002750","label":"Delayed skeletal maturation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002162","label":"Low posterior hairline","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012758","label":"Neurodevelopmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011381","label":"Aplasia of the semicircular canal","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001631","label":"Atrial septal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001156","label":"Brachydactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000978","label":"Bruising susceptibility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004209","label":"Clinodactyly of the 5th finger","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001680","label":"Coarctation of aorta","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012569","label":"Delayed menarche","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010946","label":"Dilatation of the renal pelvis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001639","label":"Hypertrophic cardiomyopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012209","label":"Juvenile myelomonocytic leukemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001004","label":"Lymphedema","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000995","label":"Melanocytic nevus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000938","label":"Osteopenia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008897","label":"Postnatal growth retardation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002974","label":"Radioulnar synostosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001328","label":"Specific learning disability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001643","label":"Patent ductus arteriosus","frequency":"Very rare (<4-1%)","criteria":null}]}}