{"orpha":487796,"name":"Takenouchi-Kosaki syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome"],"definition":"A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability characterized by global developmental delay, intellectual disability, macrothrombocytopenia, lymphedema, and dysmorphic facial features (like synophrys, ptosis, eversion of the lateral portion of the lower eyelid, and thin upper lip, among others). Additional reported manifestations include cardiac and genitourinary anomalies, sensorineural hearing loss, ophthalmologic abnormalities, skeletal anomalies, and immunodeficiency. Brain imaging may show enlarged ventricles, cerebellar atrophy, or white matter changes.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-487796/","orphanet_url":"https://www.orpha.net/en/disease/detail/487796","names":{"fr":{"name":"Syndrome Takenouchi-Kosaki","synonyms":["Syndrome de macrothrombocytopénie-lymphoedème-retard de développement-dysmorphie faciale-camptodactylie"],"definition":"Anomalies congénitales multiples/syndrome dysmorphique rare avec déficience intellectuelle, caractérisé par un retard global du développement, une déficience intellectuelle, une macrothrombocytopénie, un lymphoedème et une dysmorphie faciale (à savoir, synophridie, ptosis, éversion de la partie latérale de la paupière inférieure et lèvre supérieure fine). Les autres signes cliniques observés sont des malformations cardiaques et génito-urinaires, une surdité de perception, des anomalies ophtalmologiques, des malformations squelettiques et une immunodéficience. L'IRM met en évidence une hypertrophie des ventricules, une atrophie cérébelleuse ou des modifications de la substance blanche."},"de":{"name":"Takenouchi-Kosaki-Syndrom","definition":"Ein seltenes Fehlbildungssyndrom mit multiplen kongenitalen Anomalien/Dysmorphien, das gekennzeichnet ist durch eine globale Entwicklungsverzögerung, eine Intelligenzminderung, Makrothrombozytopenie, Lymphödeme und dysmorphe Gesichtszüge (u. a. Synophrie, Ptosis, Eversion des seitlichen Teils des Unterlids und dünne Oberlippe) Zu den weiteren berichteten Manifestationen gehören Herz- und Urogenitalanomalien, sensorineurale Schwerhörigkeit, ophthalmologische Anomalien, Skelettanomalien und Immunschwäche. Die Bildgebung des Gehirns kann vergrößerte Ventrikel, Kleinhirnatrophie oder Veränderungen der weißen Substanz zeigen."},"es":{"name":"Síndrome de Takenouchi-Kosaki","definition":"Es un síndrome dismórfico/ de múltiples anomalías congénitas poco frecuente asociado a discapacidad intelectual y caracterizado por retraso global del desarrollo, macrotrombocitopenia, linfedema y rasgos faciales dismórficos (como sinofridia, ptosis, eversión de la porción lateral del párpado inferior y labio superior fino, entre otros). Otras manifestaciones descritas incluyen anomalías cardíacas y genitourinarias, hipoacusia neurosensorial, anomalías oftalmológicas, anomalías esqueléticas e inmunodeficiencia. Las imágenes cerebrales pueden mostrar ventrículos agrandados, atrofia cerebelosa o cambios en la sustancia blanca."},"it":{"name":"Sindrome di Takenouchi-Kosaki","synonyms":["Sindrome macrotrombocitopenia-linfedema-ritardo dello sviluppo-dismorfismi facciali-camptodattilia"],"definition":"Si tratta di una malattia rara da anomalie/dismorfismi congeniti multipli associata alla disabilità intellettiva, caratterizzata da ritardo dello sviluppo globale, disabilità intellettiva, macrotrombocitopenia, linfedema e dismorfismi facciali (sinofria, ptosi, anteversione della porzione laterale della palpebra inferiore e labbro superiore sottile). I pazienti possono presentare anche cardiopatie, anomalie genitourinarie, sordità neurosensoriale, anomalie oculari e scheletriche, e immunodeficienza. Le neuroimmagini mostrano ventricoli dilatati, atrofia cerebellare o alterazioni della sostanza bianca."},"nl":{"name":"Syndroom van Takenouchi-Kosaki","definition":"Een zeldzaam meervoudige congenitale anomalieën/dysmorfie-syndroom met intellectuele achterstand, gekarakteriseerd door algehele ontwikkelingsachterstand, intellectuele beperking, macrotrombocytopenie, lymfoedeem, en dysmorfe gelaatskenmerken (zoals onder meer synophrys, ptose, eversie van lateraal deel van onderste ooglid, en dunne bovenlip). Bijkomend gerapporteerde manifestaties zijn onder meer cardiale en urogenitale anomalieën, sensorineuraal gehoorverlies, oftalmologische afwijkingen, skeletanomalieën, en immuundeficiëntie. Beeldvorming van hersenen toont mogelijk vergrote ventrikels, cerebellaire atrofie, of veranderingen van witte stof."},"pt":{"name":"Síndrome Takenouchi-Kosaki","synonyms":["Deficiência CDC42"]},"pl":{"name":"Zespół makrotrombocytopenii, obrzęku limfatycznego, opóźnienia rozwoju, dysmorfii twarzy I przykurczów palców","synonyms":["Zespół Takenouchiego i Kosakiego"]},"cs":{"name":"Syndrom zahrnující makrotrombocytopenii, lymfedém, opoždění vývoje, faciální dysmorfismus a kamptodaktylii","synonyms":["Takenouchiho-Kosakiho syndrom","Takenouchi-Kosakiho syndrom"]},"uk":{"name":"Синдром Такенучі-Косакі","synonyms":["Синдром макротромбоцитопенії-лімфедеми-затримки розвитку-дизморфізму обличчя- камптодактилії"],"definition":"A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability characterized by global developmental delay, intellectual disability, macrothrombocytopenia, lymphedema, and dysmorphic facial features (like synophrys, ptosis, eversion of the lateral portion of the lower eyelid, and thin upper lip, among others). Additional reported manifestations include cardiac and genitourinary anomalies, sensorineural hearing loss, ophthalmologic abnormalities, skeletal anomalies, and immunodeficiency. Brain imaging may show enlarged ventricles, cerebellar atrophy, or white matter changes."},"zh":{"name":"巨血小板减少-淋巴水肿-发育迟缓-面部畸形-先天性指屈曲综合征","synonyms":["Takenouchi-Kosaki综合征"],"definition":"一种罕见的多发性先天性异常/畸形综合征，伴有智力障碍，其特点是全面发育迟缓、智力障碍、巨血小板减少、淋巴水肿和面部畸形（如连眉、上睑下垂、下眼睑外侧部分外翻、上唇薄等）。其他报道的表现包括心脏和泌尿生殖系统异常、感音神经性听力损失、眼科异常、骨骼异常和免疫缺陷。脑影像学检查可显示脑室扩大、小脑萎缩或白质变化。"},"tr":{"name":"Makro trombositopeni-lenfödem-gelişme geriliği-fasiyal dismorfizm-kamptodaktili sendromu","synonyms":["Takenouchi-Kosaki sendromu"]}},"xrefs":[{"source":"OMIM","code":"616737","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.1","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0014757","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4225222","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":97992,"name":"Rare hematologic disease"},"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":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":717877,"name":"Rare miscellaneous disease with inflammatory bowel disease","classifications":[152,156,233]},{"orpha":477794,"name":"Syndromic constitutional thrombocytopenia","classifications":[156,194]}],"children":[],"genes":[{"symbol":"CDC42","name":"cell division cycle 42","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"26386261[PMID]_26708094[PMID]","hgnc":"1736","ensembl":"ENSG00000070831","omim":"116952","loci":["1p36.12"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":2.0,"area":"Worldwide","status":"Validated","source":"26708094[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_26708094[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-01-09","source":"26708094[PMID]_26386261[PMID]_29394990[PMID]","terms":[{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0410263","label":"Brain imaging abnormality","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001627","label":"Abnormal heart morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002518","label":"Abnormal periventricular white matter morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000766","label":"Abnormal sternum morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000818","label":"Abnormality of the endocrine system","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000119","label":"Abnormality of the genitourinary system","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011877","label":"Increased mean platelet volume","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008897","label":"Postnatal growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002719","label":"Recurrent infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001873","label":"Thrombocytopenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100763","label":"Abnormality of the lymphatic system","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000924","label":"Abnormality of the skeletal system","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000414","label":"Bulbous nose","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012385","label":"Camptodactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007033","label":"Cerebellar dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030084","label":"Clinodactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001305","label":"Dandy-Walker malformation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000689","label":"Dental malocclusion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002714","label":"Downturned corners of mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007655","label":"Eversion of lateral third of lower eyelids","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000577","label":"Exotropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000454","label":"Flared nostrils","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001371","label":"Flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002553","label":"Highly arched eyebrow","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000126","label":"Hydronephrosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000047","label":"Hypospadias","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002721","label":"Immunodeficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000023","label":"Inguinal hernia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001004","label":"Lymphedema","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011800","label":"Midface retrusion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000341","label":"Narrow forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003764","label":"Nevus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001845","label":"Overlapping toe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001643","label":"Patent ductus arteriosus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011220","label":"Prominent forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009623","label":"Proximal placement of thumb","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007663","label":"Reduced visual acuity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000322","label":"Short philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000319","label":"Smooth philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0045075","label":"Sparse eyebrow","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000664","label":"Synophrys","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001182","label":"Tapered finger","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010804","label":"Tented upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000219","label":"Thin upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005160","label":"Total anomalous pulmonary venous return","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000122","label":"Unilateral renal agenesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000465","label":"Webbed neck","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000154","label":"Wide mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000687","label":"Widely spaced teeth","frequency":"Occasional (29-5%)","criteria":null}]}}