{"orpha":638,"name":"Neurofibromatosis-Noonan syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["NFNS","Neurofibromatosis type 1-Noonan syndrome"],"definition":"Neurofibromatosis-Noonan syndrome (NFNS) is a RASopathy and a variant of neurofibromatosis type 1 (NF1) characterized by the combination of features of NF1, such as café-au-lait spots, iris Lisch nodules, axillary and inguinal freckling, optic nerve glioma and multiple neurofibromas, and Noonan syndrome (NS), such as short stature, typical facial features (hypertelorism, ptosis, downslanting palpebral fissures, low-set posteriorly rotated ears with a thickened helix, and a broad forehead), congenital heart defects and unusual pectus deformity. As these three entities have significant phenotypic overlap, molecular genetic testing is often necessary for a correct diagnosis (such as when café-au-lait spots are present in patients diagnosed with NS).","note":null,"url":"https://raremap.alftech.space/d/ORPHA-638/","orphanet_url":"https://www.orpha.net/en/disease/detail/638","names":{"fr":{"name":"Neurofibromatose-syndrome de Noonan","synonyms":["NFNS","Neurofibromatose type 1-syndrome de Noonan"],"definition":"RASopathie et variante de la neurofibromatose type 1 (NF1) caractérisée par l'association des caractéristiques de la NF1, à savoir taches café-au-lait, nodules de Lisch dans l'iris, taches de rousseur axillaires et inguinales, gliome du nerf optique et neurofibromes multiples, et du syndrome de Noonan (SN), à savoir petite taille, dysmorphie faciale typique (hypertélorisme, ptosis, fentes palpébrales orientées vers le bas, oreilles d'implantation basse, orientées vers l'arrière avec un hélix épaissi et un front large), malformations cardiaques congénitales et déformation inhabituelle du thorax. Compte tenu d'importants similarités phénotypiques entre ces trois entités, un test génétique moléculaire est souvent nécessaire pour établir un diagnostic exact (par exemple lorsque les taches café-au-lait sont présentes chez des patients ayant reçu un diagnostic de SN)."},"de":{"name":"Neurofibromatose-Noonan-Syndrom","synonyms":["NFNS","Neurofibromatose Typ 1-Noonan-Syndrom"]},"es":{"name":"Neurofibromatosis-síndrome de Noonan","synonyms":["NFNS","Neurofibromatosis tipo 1-síndrome de Noonan"],"definition":"Es una rasopatía y una variante de la neurofibromatosis tipo 1 (NF1) caracterizada por la combinación de características de la NF1, tales como manchas café con leche, nódulos de Lisch en el iris, pecas axilares e inguinales, glioma del nervio óptico y neurofibromas múltiples, y del síndrome de Noonan (SN), tales como talla baja, rasgos faciales característicos (hipertelorismo, ptosis, fisuras palpebrales inclinadas hacia abajo, orejas rotadas posteriormente y de baja implantación, con un hélix engrosado y frente ancha), cardiopatías congénitas y malformación del tórax. Dado que estas tres entidades tienen una importante superposición fenotípica, a menudo es necesario realizar pruebas genéticas moleculares para un diagnóstico correcto (por ejemplo, cuando hay manchas café con leche en pacientes diagnosticados de SN)."},"it":{"name":"Sindrome neurofibromatosi-Noonan","synonyms":["NFNS","Sindrome neurofibromatosi 1-Noonan"],"definition":"La sindrome neurofibromatosi - Noonan (NFNS) è una RASopatia, una variante della neurofibromatosi tipo 1 (NF1). È caratterizzata dall'associazione tra i segni clinici caratteristici della NF1 (macchie caffè-latte, noduli di Lisch nell'iride, lentigginosi ascellare e inguinale, glioma del nervo ottico e neurofibromi multipli) e quelli tipici della sindrome di Noonan (NS), come la bassa statura, i dismorfismi facciali caratteristici (ipertelorismo, ptosi, rime palpebrali oblique verso il basso, orecchie a basso impianto e ruotate posteriormente con ispessimento dell'elice e fronte ampia), le cardiopatie congenite e la deformità atipica del torace. Dato che queste malattie presentano una significativa sovrapposizione fenotipica, per una corretta diagnosi spesso si rendono necessari i test molecolari (ad esempio quando i pazienti con diagnosi di NS presentano macchie caffè-latte)."},"nl":{"name":"Neurofibromatose - syndroom van Noonan","synonyms":["NFNS","Neurofibromatose type 1 - syndroom van Noonan"],"definition":"Neurofibromatose - syndroom van Noonan (NFNS) is een RASopathie en een variant van neurofibromatose type 1 (NF1), gekarakteriseerd door de combinatie van kenmerken van NF1, zoals café-au-lait vlekken, Lisch noduli op de iris, sproetvorming in de oksel- en liesstreek, glioom van de oogzenuw en multipele neurofibromen, en kenmerken van syndroom van Noonan (NS), zoals kleine gestalte, typische gelaatskenmerken (hypertelorisme, ptose, schuin naar beneden hellende ooglidspleten, laagstaande en naar achteren gedraaide oren met een verdikte helix, en een breed voorhoofd), congenitale hartdefecten en ongewone misvorming van de pectus. Aangezien deze drie entiteiten significante fenotypische overlap vertonen, vereist een correcte diagnose vaak moleculair genetisch testen (zoals wanneer café-au-lait vlekken aanwezig zijn bij patiënten gediagnosticeerd met NS)."},"pt":{"name":"Síndrome de neurofibromatose-Noonan"},"pl":{"name":"Neurofibromatoza - zespół Noonan","synonyms":["Nerwiakowłókniakowatość typu 1-zespół Noonan","NFNS"]},"cs":{"name":"Neurofibromatóza-Noonanové syndrom","synonyms":["NFNS","Neurofibromatóza, typ I, a Noonanové syndrom","NF1-Noonanové syndrom"]},"uk":{"name":"Синдром нейрофіброматозу-Нунана","synonyms":["Нейрофіброматоз типу 1 - синдром Нуннана","NFNS"],"definition":"Neurofibromatosis-Noonan syndrome (NFNS) is a RASopathy and a variant of neurofibromatosis type 1 (NF1) characterized by the combination of features of NF1, such as café-au-lait spots, iris Lisch nodules, axillary and inguinal freckling, optic nerve glioma and multiple neurofibromas, and Noonan syndrome (NS), such as short stature, typical facial features (hypertelorism, ptosis, downslanting palpebral fissures, low-set posteriorly rotated ears with a thickened helix, and a broad forehead), congenital heart defects and unusual pectus deformity. As these three entities have significant phenotypic overlap, molecular genetic testing is often necessary for a correct diagnosis (such as when café-au-lait spots are present in patients diagnosed with NS)."},"zh":{"name":"神经纤维瘤病-努南综合征","synonyms":["神经纤维瘤病1型-努南综合征"]},"tr":{"name":"Nörofibromatoz-Noonan sendromu","synonyms":["NFNS","Nörofibromatozis tip 1-Noonan sendromu"]}},"xrefs":[{"source":"OMIM","code":"601321","qualifier":"E","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":"679913930"},{"source":"MONDO","code":"0011035","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C537393","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C2931482","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"372","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":183487,"name":"Genetic skin tumor or hamartoma","classifications":[156]},{"orpha":79375,"name":"Hyperpigmentation of the skin","classifications":[187]},{"orpha":140162,"name":"Inherited cancer-predisposing syndrome","classifications":[156,202]},{"orpha":98196,"name":"Malformation syndrome with hamartosis","classifications":[147,156]},{"orpha":98733,"name":"Noonan syndrome and Noonan-related syndrome","classifications":[147,148,156]},{"orpha":79386,"name":"Rare skin tumor or hamartoma","classifications":[187,202]}],"children":[],"genes":[{"symbol":"MAP2K2","name":"mitogen-activated protein kinase kinase 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24311457[PMID]","hgnc":"6842","ensembl":"ENSG00000126934","omim":"601263","loci":["19p13.3"]},{"symbol":"NF1","name":"neurofibromin 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22847776[PMID]","hgnc":"7765","ensembl":"ENSG00000196712","omim":"613113","loci":["17q11.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Not yet validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0009023","label":"Abdominal wall muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011039","label":"Abnormal helix morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000271","label":"Abnormality of the face","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","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:0007565","label":"Multiple cafe-au-lait spots","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001642","label":"Pulmonic stenosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001328","label":"Specific learning disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000465","label":"Webbed neck","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000765","label":"Abnormal thorax morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100763","label":"Abnormality of the lymphatic system","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003010","label":"Prolonged bleeding time","frequency":"Frequent (79-30%)","criteria":null}]}}