{"orpha":508498,"name":"Intellectual disability-cardiac anomalies-short stature-joint laxity syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Intellectual disability-cardiac anomalies-short stature-joint laxity syndrome due to mutation in PUF60 gene"],"definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by intrauterine and postnatal growth restriction, global developmental delay, intellectual disability, and dysmorphic facial features (such as broad nasal root, anteverted nares, long philtrum, low-set and posteriorly rotated ears, and short neck). Additional reported manifestations are microcephaly, short stature, vertebral abnormalities, joint laxity, ocular, cardiac, and renal defects, and minor limb anomalies. Brain imaging may show hypoplastic corpus callosum, delayed myelination, and cerebral atrophy.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-508498/","orphanet_url":"https://www.orpha.net/en/disease/detail/508498","names":{"fr":{"name":"Syndrome de déficience intellectuelle-cardiopathie congénitale-petite taille-laxité ligamentaire","synonyms":["Syndrome de déficience intellectuelle-cardiopathie congénitale-petite taille-laxité ligamentaire lié à une mutation de PUF60"],"definition":"Anomalies congénitales multiples/syndrome dysmorphique rare d'origine génétique caractérisé par un retard de croissance intra-utérine et postnatale, un retard global du développement, une déficience intellectuelle et une dysmorphie faciale (un pont nasal large, des narines antéversées, un long philtrum, des oreilles à implantation basse et inclinées en arrière, et un cou court). Les autres signes cliniques rapportés sont une microcéphalie, une petite taille, des malformations vertébrales, une laxité articulaire, des malformations oculaires, cardiaques et rénales, et des malformations mineures des membres. L'IRM peut révéler une hypoplasie du corps calleux, un retard de myélinisation et une atrophie cérébrale."},"de":{"name":"Intelligenzminderung-kardiale Anomalien-Kleinwuchs-Gelenkinstabilität-Syndrom","definition":"Ein genetisch bedingtes Dysmorphie-Syndrom, das durch intrauterine und postnatale Wachstumsbeschränkung, globale Entwicklungsverzögerung, Intelligenzminderung und Gesichtsdysmorphien (wie breite Nasenwurzel, antevertierte Nasenlöcher, langes Philtrum, tief angesetzte und nach hinten gedrehte Ohren und kurzer Hals) gekennzeichnet ist. Weitere gemeldete Manifestationen sind Mikrozephalie, Kleinwuchs, Wirbelsäulenanomalien, laxe Gelenke, Augen-, Herz- und Nierenfehler sowie kleinere Anomalien der Gliedmaßen. Die Bildgebung des Gehirns kann ein hypoplastisches Corpus callosum, eine verzögerte Myelinisierung und eine zerebrale Atrophie zeigen."},"es":{"name":"Síndrome de discapacidad intelectual-anomalías cardíacas-talla baja-laxitud articular","synonyms":["Síndrome de discapacidad intelectual-anomalías cardíacas-talla baja-laxitud articular por una mutación en el gen PUF60"],"definition":"Es un síndrome dismórfico/ de múltiples anomalías congénitas de base genética y poco frecuente caracterizado por restricción del crecimiento intrauterino y posnatal, retraso global del desarrollo, discapacidad intelectual y rasgos faciales dismórficos (como raíz nasal ancha, narinas antevertidas, filtrum largo, orejas de implantación baja en rotación posterior y cuello corto). Otras manifestaciones descritas son microcefalia, talla baja, anomalías vertebrales, laxitud articular, defectos oculares, cardíacos y renales y anomalías menores de las extremidades. La neuroimagen puede mostrar hipoplasia del cuerpo calloso, retraso del proceso de mielinización y atrofia cerebral."},"it":{"name":"Sindrome disabilità intellettiva-cardiopatie-bassa statura-lassità articolare","synonyms":["Sindrome disabilità intellettiva-cardiopatie-bassa statura-lassità articolare da mutazione del gene PUF60"],"definition":"Si tratta di una malattia genetica rara da anomalie/dismorfismi congeniti multipli, caratterizzata da ritardo della crescita pre- e postnatale, ritardo dello sviluppo globale, disabilità intellettiva e dismorfismi facciali (sella nasale ampia, narici anteverse, filtro lungo, orecchie a basso impianto ruotate posteriormente, collo corto). I pazienti possono presentare anche microcefalia, bassa statura, anomalie delle vertebre, lassità articolare, difetti oculari, cardiaci e renali, e lievi anomalie degli arti. Le neuroimmagini mostrano ipoplasia del copro calloso, ritardo della mielinizzazione e atrofia cerebrale."},"nl":{"name":"Intellectuele achterstand - hartanomalieën - kleine gestalte - gewrichtslaxiteit-syndroom","definition":"Een zeldzaam, genetisch syndroom met multipele congenitale anomalieën/dysmorfie, gekarakteriseerd door intra-uteriene en postnatale groeirestrictie, algehele ontwikkelingsachterstand, intellectuele achterstand, en dysmorfe gelaatskenmerken (zoals brede neuswortel, anteversie van neusgaten, lang filtrum, laagstaand en naar achteren gedraaide oren, en korte nek). Bijkomende manifestaties die werden gerapporteerd, zijn microcefalie, kleine gestalte, vertebrale anomalieën, gewrichtslaxiteit, defecten van oog, hart en nier, en kleine ledemaatanomalieën. Beeldvorming van hersenen toont mogelijk hypoplastisch corpus callosum, vertraagde myelinisatie, en cerebrale atrofie."},"pt":{"name":"Síndrome de perturbação do desenvolvimento intelectual-anomalias cardíacas-baixa estatura-hipermobilidade articular","synonyms":["Síndrome de perturbação do desenvolvimento intelectual-anomalias cardíacas-baixa estatura-hipermobilidade articular devido a mutação no gene PUF60"]},"pl":{"name":"Zespół niepełnosprawności intelektualnej-wad serca-niskiego wzrostu-niestabilności stawów","synonyms":["Intellectual disability-cardiac anomalies-short stature-joint laxity syndrome due to mutation in PUF60 gene"]},"cs":{"name":"Syndrom zahrnující mentální retardaci, srdeční anomálie, malý vzrůst a hypermobilitu kloubů","synonyms":["Intellectual disability-cardiac anomalies-short stature-joint laxity syndrome due to mutation in PUF60 gene"]},"uk":{"name":"Синдром інтелектуальної недостатності-серцевих аномалій-низькорослості-розхитаності суглобів","definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by intrauterine and postnatal growth restriction, global developmental delay, intellectual disability, and dysmorphic facial features (such as broad nasal root, anteverted nares, long philtrum, low-set and posteriorly rotated ears, and short neck). Additional reported manifestations are microcephaly, short stature, vertebral abnormalities, joint laxity, ocular, cardiac, and renal defects, and minor limb anomalies. Brain imaging may show hypoplastic corpus callosum, delayed myelination, and cerebral atrophy."},"zh":{"name":"智力障碍-心脏畸形-身材矮小-关节松弛综合症"},"tr":{"name":"Zihinsel yetersizlik-kardiyak anomaliler-kısa boy-eklem gevşekliği sendromu"}},"xrefs":[{"source":"OMIM","code":"615583","qualifier":"NTBT","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":"attributed","validated":true},{"source":"MONDO","code":"0034989","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5568572","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":183570,"name":"Genetic malformation syndrome with short stature","classifications":[156]},{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":139021,"name":"Malformation syndrome with short stature","classifications":[147]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":156532,"name":"Rare syndrome with cardiac malformations","classifications":[147,148,156]}],"children":[],"genes":[{"symbol":"PUF60","name":"poly(U) binding splicing factor 60","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"27804958[PMID]_28327570[PMID]","hgnc":"17042","ensembl":"ENSG00000179950","omim":"604819","loci":["8q24.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":18.0,"area":"Worldwide","status":"Validated","source":"28327570[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_28327570[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-01-22","source":"28327570[PMID]_30352594[PMID]","terms":[{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0030680","label":"Abnormal cardiovascular system morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011842","label":"Abnormality of skeletal morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001155","label":"Abnormality of the hand","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000589","label":"Coloboma","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002761","label":"Generalized joint hypermobility","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000998","label":"Hypertrichosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000308","label":"Microretrognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000219","label":"Thin upper lip vermilion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004691","label":"2-3 toe syndactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000733","label":"Abnormal repetitive mannerisms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012795","label":"Abnormality of the optic disc","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001274","label":"Agenesis of corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007874","label":"Almond-shaped palpebral fissure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000646","label":"Amblyopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001659","label":"Aortic regurgitation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006712","label":"Aplasia/Hypoplasia of the ribs","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006695","label":"Atrioventricular canal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000729","label":"Autistic behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001647","label":"Bicuspid aortic valve","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010055","label":"Broad hallux","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006009","label":"Broad phalanx","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011304","label":"Broad thumb","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012487","label":"Cerebellopontine angle arachnoid cyst","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025481","label":"Cervical hemivertebrae","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:0009997","label":"Duplication of phalanx of hand","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000565","label":"Esotropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001738","label":"Exocrine pancreatic insufficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010628","label":"Facial palsy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002949","label":"Fused cervical vertebrae","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002827","label":"Hip dislocation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000085","label":"Horseshoe kidney","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000974","label":"Hyperextensible skin","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000540","label":"Hypermetropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005620","label":"Hypermobility of interphalangeal joints","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000047","label":"Hypospadias","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000612","label":"Iris coloboma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000303","label":"Mandibular prognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000568","label":"Microphthalmia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001052","label":"Nevus flammeus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000609","label":"Optic nerve hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001845","label":"Overlapping toe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000767","label":"Pectus excavatum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000125","label":"Pelvic kidney","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011682","label":"Perimembranous ventricular septal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006970","label":"Periventricular leukomalacia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001763","label":"Pes planus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001177","label":"Preaxial hand polydactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000104","label":"Renal agenesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000089","label":"Renal hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000480","label":"Retinal coloboma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009237","label":"Short 5th finger","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004279","label":"Short palm","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012745","label":"Short palpebral fissure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003835","label":"Shoulder subluxation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002360","label":"Sleep abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002414","label":"Spina bifida","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001636","label":"Tetralogy of Fallot","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008467","label":"Thoracic hemivertebrae","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002942","label":"Thoracic kyphosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002943","label":"Thoracic scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001660","label":"Truncus arteriosus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007687","label":"Unilateral ptosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001629","label":"Ventricular septal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null}]}}