{"orpha":3071,"name":"Costello syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["FCS syndrome","Faciocutaneoskeletal syndrome"],"definition":"A rare syndrome with intellectual disability, characterized by failure to thrive, short stature, joint laxity, soft skin, and distinctive facial features. Cardiac and neurological involvement is common and there is an increased lifetime risk of certain tumors. Costello syndrome belongs to the RASopathies, a group of conditions resulting from germline derived point mutations affecting the RAS-mitogen activated protein kinase pathway.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-3071/","orphanet_url":"https://www.orpha.net/en/disease/detail/3071","names":{"fr":{"name":"Syndrome de Costello","synonyms":["Syndrome FCS","Syndrome facio-cutanéo-squelettique"],"definition":"Syndrome de déficience intellectuelle rare caractérisé par un retard de croissance, une petite taille, une hyperlaxité articulaire, une peau lâche et une dysmorphie faciale typique. Une atteinte cardiaque et neurologique est fréquente, et les patients sont à plus haut risque de tumeurs tout au long de leur vie. Le syndrome de Costello fait partie des RASopathies, un groupe de maladies dues à des mutations ponctuelles dérivées de lignées germinales qui touchent la voie RAS/MAP kinases."},"de":{"name":"Costello-Syndrom","synonyms":["FCS-Syndrom","Fazio-kutano-skelettales Syndrom"],"definition":"Ein seltenes Syndrom mit Intelligenzminderung, gekennzeichnet durch Gedeihstörung, Kleinwuchs, Gelenklaxität, weiche Haut und ausgeprägte Gesichtszüge. Eine kardiale und neurologische Beteiligung ist häufig und es besteht ein erhöhtes Lebenszeitrisiko für bestimmte Tumore. Das Costello-Syndrom gehört zu den RASopathien, einer Gruppe von Erkrankungen, die aus Keimbahn-Punktmutationen resultieren, die den RAS-Mitogen-aktivierten Proteinkinase-Signalweg betreffen."},"es":{"name":"Síndrome de Costello","synonyms":["Síndrome FCS","Síndrome facio-cutáneo-esquelético"],"definition":"Es un síndrome poco frecuente con discapacidad intelectual caracterizado por fallo de medro, talla baja, laxitud articular, piel suave y rasgos faciales distintivos. La afectación cardíaca y neurológica es común y existe un mayor riesgo de por vida de desarrollar ciertos tumores. El síndrome de Costello pertenece a las RASopatías, un grupo de afecciones resultantes de mutaciones puntuales en la línea germinal que afectan a la vía RAS de las proteín quinasas activada por mitógenos."},"it":{"name":"Sindrome di Costello","synonyms":["Sindrome FCS","Sindrome facio-cutaneo-scheletrica"],"definition":"La sindrome di Costello (CS) è una malattia rara associata a disabilità intellettiva, caratterizzata da ritardo della crescita, bassa statura, lassità articolare, cute soffice e dismorfismi facciali caratteristici. Sono comuni l'interessamento cardiaco e neurologico. Per tutta la vita, i pazienti presentano un aumento del rischio di alcuni tipi di tumore. La CS appartiene al gruppo delle RASopatie, malattie causate da mutazioni puntiformi derivate dalla linea germinale che interessano la via della MAP-chinasi attivata da RAS."},"nl":{"name":"Syndroom van Costello","synonyms":["FCS-syndroom","Faciocutaneoskeletaal syndroom"],"definition":"Een zeldzaam syndroom met intellectuele achterstand, gekarakteriseerd door groeifalen, kleine gestalte, gewrichtslaxiteit, zachte huid, en typische gelaatskenmerken. Cardiale en neurologische betrokkenheid is gangbaar en er is een levenslang verhoogd risico op bepaalde tumoren. Syndroom van Costello behoort tot de RASopathieën, een groep van condities die het gevolg zijn van puntmutaties afkomstig van kiembaancellen die de RAS-mitogeen geactiveerde proteïnekinase signaalweg beïnvloeden."},"pt":{"name":"Síndrome Costello","synonyms":["Perturbação do desenvolvimento intelectual-papilomas nasais","Síndrome FCS","Síndrome facio-cutâneo-esquelético"]},"pl":{"name":"Zespół Costello","synonyms":["Zespół FCS","Zespół twarzowo-skórno-szkieletowy"],"definition":"Rzadki zespół niepełnosprawności intelektualnej, charakteryzujący się brakiem prawidłowego rozwoju, niskim wzrostem, wiotkością stawów, miękką skórą i charakterystycznymi rysami twarzy. Często występują zmiany kardiologiczne i neurologiczne, a ryzyko wystąpienia niektórych nowotworów w ciągu całego życia jest zwiększone. Zespół Costello należy do RASopatii, grupy schorzeń związanych z germinalnymi mutacjami punktowymi wpływających na szlak kinazy białkowej aktywowanej mitogenami RAS."},"cs":{"name":"Costellův syndrom","synonyms":["FCS syndrom","Faciokutaneoskeletální syndrom"]},"uk":{"name":"Синдром Костелло","synonyms":["Лицево-кишково-суглобовий синдром","Синдром FCS"],"definition":"A rare syndrome with intellectual disability, characterized by failure to thrive, short stature, joint laxity, soft skin, and distinctive facial features. Cardiac and neurological involvement is common and there is an increased lifetime risk of certain tumors. Costello syndrome belongs to the RASopathies, a group of conditions resulting from germline derived point mutations affecting the RAS-mitogen activated protein kinase pathway."},"zh":{"name":"Costello综合征","synonyms":["面皮肤骨骼综合征"]},"tr":{"name":"Costello sendromu","synonyms":["FCS sendromu","Fasiyokütanoskeletal sendrom"]}},"xrefs":[{"source":"OMIM","code":"218040","qualifier":"E","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":"1946512039"},{"source":"MONDO","code":"0009026","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D056685","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0587248","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"1550","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10067380","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":228215,"name":"Genetic dermis elastic tissue disorder","classifications":[156,187]},{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"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":139027,"name":"Rare developmental defect with skin/mucosae involvement","classifications":[147,156]},{"orpha":477771,"name":"Rare disorder with a moyamoya angiopathy","classifications":[156,181]},{"orpha":217595,"name":"Syndrome associated with hypertrophic cardiomyopathy","classifications":[146,156,233]}],"children":[],"genes":[{"symbol":"HRAS","name":"HRas proto-oncogene, GTPase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (gain of function) in","status":"Assessed","source":"20301680[PMID]","hgnc":"5173","ensembl":"ENSG00000174775","omim":"190020","loci":["11p15.5"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant","Not applicable"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":300.0,"area":"Worldwide","status":"Validated","source":"20301680[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"<1 / 1 000 000","value":0.08,"area":"Japan","status":"Validated","source":"22495831[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":"2025-12-03","source":"40116115[PMID]","terms":[{"hpo":"HP:0001231","label":"Abnormal fingernail morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000951","label":"Abnormality of the skin","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000956","label":"Acanthosis nigricans","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001598","label":"Concave nail","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001814","label":"Deep-set nails","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002750","label":"Delayed skeletal maturation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0005280","label":"Depressed nasal bridge","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001531","label":"Failure to thrive in infancy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000962","label":"Hyperkeratosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0100679","label":"Lack of skin elasticity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000256","label":"Macrocephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000189","label":"Narrow palate","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:0001582","label":"Redundant skin","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001629","label":"Ventricular septal defect","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002224","label":"Woolly hair","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007477","label":"Abnormal dermatoglyphics","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000682","label":"Abnormality of dental enamel","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000164","label":"Abnormality of the dentition","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000483","label":"Astigmatism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000293","label":"Full cheeks","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001639","label":"Hypertrophic cardiomyopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001800","label":"Hypoplastic toenails","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000563","label":"Keratoconus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000158","label":"Macroglossia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001634","label":"Mitral valve prolapse","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000543","label":"Optic disc pallor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012740","label":"Papilloma","frequency":"Frequent 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hyperpigmentation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000540","label":"Hypermetropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009748","label":"Large earlobe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100729","label":"Large face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002033","label":"Poor suck","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Occasional (29-5%)","criteria":null}]}}