{"orpha":261494,"name":"Kleefstra syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare genetic, intellectual disability syndrome characterized by intellectual disability, childhood hypotonia, severe expressive speech delay, autism spectrum disorder, and a distinctive facial appearance with a spectrum of additional clinical features.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-261494/","orphanet_url":"https://www.orpha.net/en/disease/detail/261494","names":{"fr":{"name":"Syndrome de Kleefstra","definition":"Syndrome rare de déficience intellectuelle d'origine génétique, caractérisé par une déficience intellectuelle, une hypotonie infantile, un retard sévère de langage expressif, un trouble du spectre autistique et une dysmorphie faciale caractéristique, associés à d'autres signes cliniques."},"de":{"name":"Kleefstra-Syndrom","definition":"Ein genetisch bedingtes Syndrom mit Intelligenzminderung, das durch intellektuelle Beeinträchtigung, Hypotonie im Kindesalter, schwere expressive Sprachentwicklungsstörung, Autismus-Spektrum-Störungen und ein charakteristisches Gesichtsbild mit einer Reihe zusätzlicher klinischer Merkmale gekennzeichnet ist."},"es":{"name":"Síndrome de Kleefstra","definition":"Es un síndrome de discapacidad intelectual, de origen genético y poco frecuente, caracterizado por discapacidad intelectual, hipotonía infantil, grave retraso del lenguaje expresivo, trastorno del espectro autista y una apariencia facial distintiva con un espectro de rasgos clínicos adicionales."},"it":{"name":"Sindrome di Kleefstra","definition":"La sindrome di Kleefstra (KS) è una malattia genetica rara da disabilità intellettiva, caratterizzata da disabilità intellettiva, ipotonia infantile, grave ritardo nel linguaggio espressivo, disturbi dello spettro autistico, facies tipica e una serie di altri segni clinici."},"nl":{"name":"Syndroom van Kleefstra","definition":"Een zeldzaam, genetisch syndroom van intellectuele achterstand, gekenmerkt door intellectuele achterstand, in de kindertijd optredende hypotonie, ernstige expressieve taalachterstand, autismespectrumstoornis, en typische gelaatstrekken, met een spectrum van bijkomende klinische kenmerken."},"pt":{"name":"Síndrome de Kleefstra","definition":"A síndrome Kleefstra (KS) é uma doença genética caracterizada por défice intelectual, hipotonia na infância, grave atraso de linguagem expressiva e uma aparência facial característica, com um espectro de outras características clínicas adicionais."},"pl":{"name":"Zespół Kleefstra"},"cs":{"name":"Kleefstrové syndrom"},"uk":{"name":"Синдром Клефстри","definition":"A rare genetic, intellectual disability syndrome characterized by intellectual disability, childhood hypotonia, severe expressive speech delay, autism spectrum disorder, and a distinctive facial appearance with a spectrum of additional clinical features."},"zh":{"name":"Kleefstra综合征","definition":"Kleefstra综合征(Kleefstra syndrome，KS)是一种遗传性疾病，特征是智力障碍、儿童期肌张力低下、严重的语言表达延迟和独特的面部外观，并有一系列额外的临床特征。"},"tr":{"name":"Kleefstra sendromu"}},"xrefs":[{"source":"OMIM","code":"610253","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":"1997337437"},{"source":"MONDO","code":"0012455","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4551771","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"8672","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10079365","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":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]}],"children":[{"orpha":96147,"name":"Kleefstra syndrome due to 9q34 microdeletion","type":"Etiological subtype"},{"orpha":261652,"name":"Kleefstra syndrome due to a point mutation","type":"Etiological subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"EHMT1","name":"euchromatic histone lysine methyltransferase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20945554[PMID]","hgnc":"24650","ensembl":"ENSG00000181090","omim":"607001","loci":["9q34.3"],"via":{"orpha":261652,"name":"Kleefstra syndrome due to a point mutation"}},{"symbol":"KMT2C","name":"lysine methyltransferase 2C","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"29069077[PMID]","hgnc":"13726","ensembl":"ENSG00000055609","omim":"606833","loci":["7q36.1"],"via":{"orpha":261652,"name":"Kleefstra syndrome due to a point mutation"}},{"symbol":"EHMT1","name":"euchromatic histone lysine methyltransferase 1","gene_type":"gene with protein product","association":"Role in the phenotype of","status":"Assessed","source":"20945554[PMID]","hgnc":"24650","ensembl":"ENSG00000181090","omim":"607001","loci":["9q34.3"],"via":{"orpha":96147,"name":"Kleefstra syndrome due to 9q34 microdeletion"}}],"inheritance":["Autosomal dominant"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":114.0,"area":"Worldwide","status":"Validated","source":"22670141[PMID]_[EXPERT]"},{"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":"2018-01-17","source":null,"terms":[{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000280","label":"Coarse facial features","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000232","label":"Everted lower lip vermilion","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002263","label":"Exaggerated cupid's bow","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000272","label":"Malar flattening","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003196","label":"Short nose","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010804","label":"Tented upper lip vermilion","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000718","label":"Aggressive behavior","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011675","label":"Arrhythmia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000729","label":"Autistic behavior","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001647","label":"Bicuspid aortic valve","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000248","label":"Brachycephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000337","label":"Broad forehead","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000389","label":"Chronic otitis media","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001680","label":"Coarctation of aorta","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002019","label":"Constipation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002553","label":"Highly arched eyebrow","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000158","label":"Macroglossia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000303","label":"Mandibular prognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001513","label":"Obesity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000742","label":"Self-mutilation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002360","label":"Sleep abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000664","label":"Synophrys","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000391","label":"Thickened helices","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001629","label":"Ventricular septal defect","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000733","label":"Abnormal repetitive mannerisms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006288","label":"Advanced eruption of teeth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001274","label":"Agenesis of corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002607","label":"Bowel incontinence","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000684","label":"Delayed eruption of teeth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002714","label":"Downturned corners of mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002094","label":"Dyspnea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000324","label":"Facial asymmetry","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100790","label":"Hernia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000126","label":"Hydronephrosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008736","label":"Hypoplasia of penis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000047","label":"Hypospadias","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001376","label":"Limitation of joint mobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000054","label":"Micropenis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004415","label":"Pulmonary artery stenosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002021","label":"Pyloric stenosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002205","label":"Recurrent respiratory infections","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000107","label":"Renal cyst","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000083","label":"Renal insufficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100716","label":"Self-injurious behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002558","label":"Supernumerary nipple","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001762","label":"Talipes equinovarus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001636","label":"Tetralogy of Fallot","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002779","label":"Tracheomalacia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000076","label":"Vesicoureteral reflux","frequency":"Occasional (29-5%)","criteria":null}]}}