{"orpha":500,"name":"Noonan syndrome with multiple lentigines","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Cardiomyopathic lentiginosis","Familial multiple lentigines syndrome","LEOPARD syndrome"],"definition":"A rare multisystem genetic disorder characterized by cutaneous lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-500/","orphanet_url":"https://www.orpha.net/en/disease/detail/500","names":{"fr":{"name":"Syndrome de Noonan avec lentigines multiples","synonyms":["Lentiginose cardiomyopathique","Syndrome LEOPARD","Syndrome des lentigines multiples familial"],"definition":"Maladie génétique multisystémique rare caractérisée par des lentigines cutanées, une cardiomyopathie hypertrophique, une petite taille, une déformation du thorax et une dysmorphie faciale."},"de":{"name":"Noonan-Syndrom mit multiplen Lentigines","synonyms":["Familiäres multiples Lentigines-Syndrom","LEOPARD-Syndrom","Lentiginose, kardiomyopathische"],"definition":"Eine seltene genetische Multisystemerkrankung, die durch kutane Lentigines, hypertrophe Kardiomyopathie, Kleinwuchs, Pektusfehlbildung und dysmorphe Gesichtszüge gekennzeichnet ist."},"es":{"name":"Síndrome de Noonan con léntigos múltiples","synonyms":["Lentiginosis cardiomiopática","Síndrome LEOPARD","Síndrome familiar de léntigos múltiples"],"definition":"Es un trastorno genético multisistémico poco frecuente caracterizado por léntigos cutáneos, miocardiopatía hipertrófica, talla baja, malformaciones torácicas y rasgos faciales dismórficos."},"it":{"name":"Sindrome di Noonan con lentiggini multiple","synonyms":["Lentigginosi cardiomiopatica","Sindrome LEOPARD","Sindrome familiare da lentiggini multiple"],"definition":"La Sindrome di Noonan con lentiggini multiple (NSML) è una malattia genetica multisistemica rara, caratterizzata da lentiggini cutanee, cardiomiopatia ipertrofica, bassa statura, deformità del torace e dismorfismi facciali."},"nl":{"name":"Syndroom van Noonan met meervoudige lentigines","synonyms":["Cardiomyopathische lentiginose","Familiale meervoudige lentigines-syndroom","LEOPARD-syndroom"],"definition":"Een zeldzame, multisystemische, genetische aandoening, gekarakteriseerd door cutane lentigines, hypertrofische cardiomyopathie, kleine gestalte, misvorming van borstwand, en dysmorfe gelaatskenmerken."},"pt":{"name":"Síndrome Noonan com lentigos múltiplos","synonyms":["Lentiginose cardiomiopática","Síndrome LEOPARD"],"definition":"A síndrome de LEOPARD (LS) é uma doença congénita rara, caracterizada principalmente por múltiplas anomalias cutâneas, faciais e cardíacas. LEOPARD é um acrónimo para as características mais importantes desta doença, incluindo Lentigos múltiplos, anomalias de condução no ECG, hipertelorismo ocular, estenose pulmonar, anomalias genitais, atraso de crescimento e surdez neurossensorial."},"pl":{"name":"Zespół Noonan z mnogimi plamami soczewicowatymi","synonyms":["Mnogie plamy soczewicowate i kardiomiopatia","Rodzinny zespół mnogich plam soczewicowatych","Zespół LEOPARD"]},"cs":{"name":"Noonanové syndrom s mnohočetnými lentiginózními pigmentacemi","synonyms":["Kardiomyopatická lentiginóza","LEOPARD syndrom","Familiární syndrom mnohočetných lenitginózních névů"]},"uk":{"name":"Синдром Нунана з множинними пігментними плямами","synonyms":["Кардіоміопатичний лентигіноз","Сімейний синдром множинного лентігінозу","Синдром LEOPARD"],"definition":"A rare multisystem genetic disorder characterized by cutaneous lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features."},"zh":{"name":"努南综合征伴多发雀斑样痣","synonyms":["家族性多发性雀斑样痣综合征"]},"tr":{"name":"Çoklu lentijinler ile Noonan sendromu","synonyms":["LEOPARD sendromu","Kardiyomiyopatik lentiginoz","Ailesel multi lentijin sendromu"]}},"xrefs":[{"source":"OMIM","code":"151100","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"611554","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"613707","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.1","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD2F.1Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"939197023"},{"source":"MONDO","code":"0007893","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D044542","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0175704","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"1100","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10062901","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":183466,"name":"Genetic hyperpigmentation of the skin","classifications":[156]},{"orpha":330206,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual disability","classifications":[156]},{"orpha":79375,"name":"Hyperpigmentation of the skin","classifications":[187]},{"orpha":619340,"name":"Inherited hematologic cancer-predisposing syndrome","classifications":[156,202]},{"orpha":98196,"name":"Malformation syndrome with hamartosis","classifications":[147,156]},{"orpha":102285,"name":"Multiple congenital anomalies/dysmorphic syndrome without intellectual disability","classifications":[147]},{"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":139027,"name":"Rare developmental defect with skin/mucosae involvement","classifications":[147,156]},{"orpha":90642,"name":"Rare syndromic genetic deafness","classifications":[147,156,200]},{"orpha":217595,"name":"Syndrome associated with hypertrophic cardiomyopathy","classifications":[146,156,233]}],"children":[],"genes":[{"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) in","status":"Assessed","source":"20301557[PMID]","hgnc":"9829","ensembl":"ENSG00000132155","omim":"164760","loci":["3p25.2"]},{"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":"20301557[PMID]","hgnc":"1097","ensembl":"ENSG00000157764","omim":"164757","loci":["7q34"]},{"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":"20301557[PMID]","hgnc":"9644","ensembl":"ENSG00000179295","omim":"176876","loci":["12q24.13"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":296.0,"area":"Worldwide","status":"Validated","source":"21500339[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:0001641","label":"Abnormal pulmonary valve morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000078","label":"Abnormality of the genital system","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004414","label":"Abnormality of the pulmonary artery","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011675","label":"Arrhythmia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011710","label":"Bundle branch block","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001480","label":"Freckling","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000974","label":"Hyperextensible skin","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001639","label":"Hypertrophic cardiomyopathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000995","label":"Melanocytic nevus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001003","label":"Multiple lentigines","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001642","label":"Pulmonic stenosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008625","label":"Severe sensorineural hearing impairment","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0030680","label":"Abnormal cardiovascular system morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001633","label":"Abnormal mitral valve morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000271","label":"Abnormality of the face","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006695","label":"Atrioventricular canal defect","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000144","label":"Decreased fertility","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001634","label":"Mitral valve prolapse","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000768","label":"Pectus carinatum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000767","label":"Pectus excavatum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003691","label":"Scapular winging","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000912","label":"Sprengel anomaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000465","label":"Webbed neck","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100542","label":"Abnormal localization of kidney","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004306","label":"Abnormality of the endocardium","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001608","label":"Abnormality of the voice","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010318","label":"Aplasia/Hypoplasia of the abdominal wall musculature","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000248","label":"Brachycephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002617","label":"Dilatation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007392","label":"Excessive wrinkled skin","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000047","label":"Hypospadias","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001256","label":"Intellectual disability, mild","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002861","label":"Melanoma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002863","label":"Myelodysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001658","label":"Myocardial infarction","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003006","label":"Neuroblastoma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003298","label":"Spina bifida occulta","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001482","label":"Subcutaneous nodule","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000325","label":"Triangular face","frequency":"Occasional (29-5%)","criteria":null}]}}