{"orpha":500150,"name":"ZTTK syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Facial dysmorphism-brain malformations-musculoskeletal abnormalities-intellectual disability syndrome","Zhu-Tokita-Takenouchi-Kim syndrome"],"definition":"A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by developmental delay, intellectual disability and mild to moderate facial dysmorphism in association with variable brain malformations (including abnormal gyration patterns, ventriculomegaly, white matter abnormalities, hypoplasia of the corpus callosum and cerebellar hemispheres), musculoskeletal abnormalities (including hemivertebrae, scoliosis or kyphosis, contractures, and joint laxity), ocular involvement (strabismus, hypermetropia and cortical visual impairment) and hypotonia. Additional clinical manifestations may include seizures, short stature urogenital malformations, heart defects and gastrointestinal malformations.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-500150/","orphanet_url":"https://www.orpha.net/en/disease/detail/500150","names":{"fr":{"name":"Syndrome ZTTK","synonyms":["Syndrome de Zhu-Tokita-Takenouchi-Kim","Syndrome de dysmorphie faciale-malformations cérébrales-anomalies musculosquelettiques-déficience intellectuelle"],"definition":"Anomalies congénitales multiples/syndrome dysmorphique rare d'origine génétique caractérisé par un retard de développement, une déficience intellectuelle et une dysmorphie faciale légère à modérée en association avec des malformations cérébrales variables (y compris, anomalies de la gyration, ventriculomégalie, anomalies de la substance blanche, hypoplasie du corps calleux et des hémisphères cérébelleux), des anomalies musculosquelettiques (y compris, hémivertèbres, scoliose ou cyphose, contractures et laxité articulaire), une atteinte oculaire (strabisme, hypermétropie et déficience visuelle corticale) et une hypotonie. Les autres manifestations cliniques peuvent inclure des crises d'épilepsie, une petite taille, des malformations urogénitales, cardiaques et gastro-intestinales."},"de":{"name":"ZTTK-Syndrom","synonyms":["Zhu-Tokita-Takenouchi-Kim-Syndrom","Hirnfehlbildung-muskuloskelettale Anomalien-Gesichtsdysmorphie-Intelligenzminderung-Syndrom"],"definition":"Ein genetisch bedingtes Dysmorphie-Syndrom, das durch Entwicklungsverzögerung, Intelligenzminderung und leichte bis mittelschwere Gesichtsdysmorphien in Verbindung mit variablen Fehlbildungen des Gehirns (einschließlich anormaler Gyrationsmuster, Ventrikulomegalie, Anomalien der weißen Substanz, Hypoplasie des Corpus callosum und der Kleinhirnhemisphären), Muskel-Skelett-Anomalien (einschließlich Halbwirbel, Skoliose oder Kyphose, Kontrakturen und Gelenkhypermobilität), Augenbeteiligung (Strabismus, Hypermetropie und kortikale Sehstörungen) und Hypotonie. Weitere klinische Manifestationen können Krampfanfälle, Kleinwuchs, urogenitale Fehlbildungen, Herzfehler und gastrointestinale Fehlbildungen sein."},"es":{"name":"Síndrome ZTTK","synonyms":["Síndrome de Zhu-Tokita-Takenouchi-Kim","Síndrome de dismorfia facial-malformaciones cerebrales-anomalías musculoesqueléticas-discapacidad intelectual"],"definition":"Es un síndrome dismórfico/con múltiples anomalías congénitas, de origen genético y poco frecuente caracterizado por retraso psicomotor, discapacidad intelectual y dismorfia facial de leve a moderada asociado a malformaciones cerebrales variables (incluyendo patrón giral anómalo, ventriculomegalia, anomalías de la sustancia blanca e hipoplasia del cuerpo calloso y de los hemisferios cerebelosos), anomalías musculoesqueléticas (tales como hemivértebras, escoliosis o cifosis, contracturas y laxitud articular), afectación ocular (estrabismo, hipermetropía y afectación visual cortical) e hipotonía. Otras manifestaciones clínicas son: crisis epilépticas, malformaciones urogenitales, talla baja, defectos cardíacos y malformaciones gastrointestinales."},"it":{"name":"Sindrome ZTTX","synonyms":["Sindrome Zhu-Tokita-Takenouchi-Kim","Sindrome dismorfismi facciali-malformazioni cerebrali-anomalie muscoloscheletriche-disabilità intellettiva"],"definition":"Si tratta di una malattia genetica rara da anomalie/dismorfismi congeniti multipli, caratterizzata da ritardo dello sviluppo, disabilità intellettiva e dismorfismi facciali lievi-moderati associati a malformazioni cerebrali variabili (anomalie delle circonvoluzioni, ventricolomegalia, anomalie della sostanza bianca, ipoplasia del corpo calloso e degli emisferi cerebellari), anomalie muscoloscheletriche (emivertebre, scoliosi o cifosi, contratture e lassità articolare), coinvolgimento oculare (strabismo, ipermetropia, compromissione della vista di origine corticale) e ipotonia. I pazienti possono presentare anche crisi epilettiche, bassa statura, malformazioni urogenitali, cardiopatie e malformazioni gastrointestinali."},"nl":{"name":"ZTTK-syndroom","synonyms":["Faciale dysmorfie - hersenmalformaties - musculoskeletale afwijkingen - intellectuele achterstand-syndroom","Syndroom van Zhu-Tokita-Takenouchi-Kim"],"definition":"Een zeldzaam, genetisch syndroom met multipele congenitale anomalieën/dysmorfie, gekenmerkt door ontwikkelingsachterstand, intellectuele achterstand, en milde tot matige faciale dysmorfie, in associatie met variabele hersenmalformaties (waaronder abnormale gyratiepatronen, ventriculomegalie, afwijkingen van witte stof, hypoplasie van corpus callosum en cerebellaire hemisferen), musculoskeletale afwijkingen (waaronder hemivertebrae, scoliose of kyfose, contracturen, en gewrichtslaxiteit), oculaire betrokkenheid (strabisme, hypermetropie en corticale visuele stoornis), en hypotonie. Mogelijke bijkomende klinische manifestaties zijn onder meer insulten, kleine gestalte, urogenitale malformaties, hartdefecten, en gastro-intestinale malformaties."},"pt":{"name":"Malformação cerebral - anormalidades musculoesqueléticas - dismorfismo facial - síndrome da deficiência intelectual"},"pl":{"name":"Zespół ZTTK","synonyms":["Zespół Zhu,Tokita, Takenouchi i Kima"]},"cs":{"name":"Syndrom vrozených vad mozku, muskuloskeletálních abnormalit, faciálního dysmorfismu a intelektové nedostatečnosti","synonyms":["Facial dysmorphism-brain malformations-musculoskeletal abnormalities-intellectual disability syndrome","Zhu-Tokita-Takenouchi-Kim syndrome"]},"uk":{"name":"Синдром вад розвитку головного мозку-аномалій опорно-рухового апарату-дисморфізму обличчя-інтелектуальної недостатності","synonyms":["Синдром Чжу-Токіта-Такеноучі-Кіма","Синдром ZTTK"],"definition":"A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by developmental delay, intellectual disability and mild to moderate facial dysmorphism in association with variable brain malformations (including abnormal gyration patterns, ventriculomegaly, white matter abnormalities, hypoplasia of the corpus callosum and cerebellar hemispheres), musculoskeletal abnormalities (including hemivertebrae, scoliosis or kyphosis, contractures, and joint laxity), ocular involvement (strabismus, hypermetropia and cortical visual impairment) and hypotonia. Additional clinical manifestations may include seizures, short stature urogenital malformations, heart defects and gastrointestinal malformations."},"zh":{"name":"脑畸形-肌肉骨骼异常-面部畸形-智力障碍综合征","synonyms":["Zhu-Tokita-Takenouchi-Kim综合征"],"definition":"一种罕见的遗传性多发性先天异常/畸形综合征，其特点是发育迟缓和智力障碍，与大脑畸形有关（包括脑回异常、脑室肥大、白质异常以及胼胝体和小脑半球发育不全）。面部畸形（包括面部不对称、中面部后缩、眼睛深陷、下睑裂、低位耳、鼻梁宽而凹陷、短人中）和肌肉骨骼异常（包括半椎体、脊柱侧凸或后凸、挛缩和关节松弛）。其他临床表现包括癫痫发作、斜视、视力下降、泌尿生殖系统畸形、心脏缺陷和身材矮小。"},"tr":{"name":"Beyin malformasyonları-kas-iskelet sistemi anormallikleri-yüz dismorfizmi-zihinsel yetersizlik sendromu","synonyms":["ZTTK sendromu","Zhu-Tokita-Takenouchi-Kim sendromu"]}},"xrefs":[{"source":"OMIM","code":"617140","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0014936","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4310696","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"13489","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10081208","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":269564,"name":"Genetic syndrome with a central nervous system malformation as a major feature","classifications":[156]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":269531,"name":"Other syndrome with a central nervous system malformation as a major feature","classifications":[147,181]}],"children":[],"genes":[{"symbol":"SON","name":"SON DNA and RNA binding protein","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"27545680[PMID]_27545676[PMID]_27256762[PMID]","hgnc":"11183","ensembl":"ENSG00000159140","omim":"182465","loci":["21q22.11"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":33.0,"area":"Worldwide","status":"Validated","source":"32926520[PMID]_27545680[PMID]_27545676[PMID]_27256762[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_27545680[PMID]_27545676[PMID]_27256762[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-02-08","source":"25590979[PMID]_27545676[PMID]_27545680[PMID]_27256762[PMID]","terms":[{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012443","label":"Abnormality of brain morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002538","label":"Abnormality of the cerebral cortex","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000119","label":"Abnormality of the genitourinary system","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000729","label":"Autistic behavior","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001531","label":"Failure to thrive in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002197","label":"Generalized-onset seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000540","label":"Hypermetropia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003508","label":"Proportionate short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002500","label":"Abnormal cerebral white matter morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0430021","label":"Abnormal common carotid artery morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001627","label":"Abnormal heart morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011467","label":"Absent gallbladder","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009777","label":"Absent thumb","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001166","label":"Arachnodactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100702","label":"Arachnoid cyst","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001631","label":"Atrial septal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008765","label":"Auditory hallucinations","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000193","label":"Bifid uvula","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012582","label":"Bilateral renal dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000592","label":"Blue sclerae","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007933","label":"Broad lateral eyebrow","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100307","label":"Cerebellar hemisphere hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100704","label":"Cerebral visual impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000891","label":"Cervical ribs","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002308","label":"Chiari malformation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002028","label":"Chronic diarrhea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000175","label":"Cleft palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002212","label":"Curly hair","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004315","label":"Decreased circulating IgG level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000490","label":"Deeply set eye","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005280","label":"Depressed nasal bridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","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:0002015","label":"Dysphagia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006989","label":"Dysplastic corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002097","label":"Emphysema","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000565","label":"Esotropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000577","label":"Exotropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000324","label":"Facial asymmetry","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025116","label":"Fetal distress","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002007","label":"Frontal bossing","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000293","label":"Full cheeks","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002579","label":"Gastrointestinal dysmotility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002578","label":"Gastroparesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011471","label":"Gastrostomy tube feeding in infancy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002121","label":"Generalized non-motor (absence) seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002283","label":"Global brain atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002937","label":"Hemivertebrae","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000085","label":"Horseshoe kidney","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010485","label":"Hyperextensibility at elbow","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005639","label":"Hyperextensible hand joints","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000327","label":"Hypoplasia of the maxilla","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002140","label":"Ischemic stroke","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002751","label":"Kyphoscoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006956","label":"Lateral ventricle dilatation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002938","label":"Lumbar hyperlordosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011330","label":"Metopic synostosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000341","label":"Narrow forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000609","label":"Optic nerve hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011648","label":"Patent ductus arteriosus after birth at term","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006970","label":"Periventricular leukomalacia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002126","label":"Polymicrogyria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007100","label":"Progressive ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000529","label":"Progressive visual loss","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011220","label":"Prominent forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000411","label":"Protruding ear","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002719","label":"Recurrent infections","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004482","label":"Relative macrocephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000902","label":"Rib fusion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004442","label":"Sagittal craniosynostosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004433","label":"Secretory IgA deficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003196","label":"Short nose","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000322","label":"Short philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009879","label":"Simplified gyral pattern","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003100","label":"Slender long bone","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000319","label":"Smooth philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001027","label":"Soft, doughy skin","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0045075","label":"Sparse eyebrow","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011819","label":"Submucous cleft soft palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000233","label":"Thin vermilion border","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002326","label":"Transient ischemic attack","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030707","label":"Unilateral lung agenesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000122","label":"Unilateral renal agenesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Occasional (29-5%)","criteria":null}]}}