{"orpha":199,"name":"Cornelia de Lange syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Brachmann-de Lange syndrome"],"definition":"A rare multiple congenital anomalies syndrome characterized by facial dysmorphism, hypertrichosis, mild to profound intellectual disability, intrauterine growth restriction (IUGR) and/or postnatal growth restriction, feeding difficulties, abnormalities of the hands and feet (ranging from severe reductional limb abnormalities, oligodactyly, to brachymetacarpia of the first metacarpus). Variable visceral malformations may be present.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-199/","orphanet_url":"https://www.orpha.net/en/disease/detail/199","names":{"fr":{"name":"Syndrome de Cornelia de Lange","synonyms":["Syndrome de Brachmann-de Lange"],"definition":"Syndrome malformatif rare caractérisé par une dysmorphie faciale, une hypertrichose, une déficience intellectuelle légère à profonde, un retard de croissance intra-utérin (RCIU) et/ou postnatal, des difficultés alimentaires, des anomalies des mains et des pieds (allant d'anomalies réductionnelles sévères, d'oligodactylies, à une brachymétacarpie du premier rayon). Diverses malformations d'organes peuvent être présentes."},"de":{"name":"Cornelia de Lange-Syndrom","synonyms":["Brachmann-de Lange-Syndrom"],"definition":"Ein seltenes Syndrom mit multiplen angeborenen Fehlbildungen, gekennzeichnet durch Gesichtsdysmorphien, Hypertrichose, leichte bis schwere Intelligenzminderung, intrauterine und/oder postnatale Wachstumsretardierung, Ernährungsprobleme, Hand- und Fußanomalien (von schweren reduktiven Gliedmaßenanomalien über Oligodaktylie bis zur Brachymetakarpie des ersten Mittelhandknochens). Viszerale Fehlbildungen können unterschiedlich ausgeprägt sein."},"es":{"name":"Síndrome de Cornelia de Lange","definition":"Es un síndrome poco frecuente de múltiples anomalías congénitas caracterizado por dismorfia facial, hipertricosis, discapacidad intelectual de leve a profunda, restricción del crecimiento intrauterino (RCIU) y/o restricción del crecimiento posnatal, dificultades de alimentación, anomalías en las manos y los pies (desde anomalías de reducción grave de las extremidades, u oligodactilia, a braquimetacarpia del primer metacarpo). Pueden estar presentes malformaciones viscerales variables."},"it":{"name":"Sindrome di Cornelia de Lange","synonyms":["Sindrome di Brachmann-de Lange"],"definition":"La sindrome di Cornelia de Lange (CdLS) è una malattia rara da anomalie congenite multiple, caratterizzata da dismorfismi facciali, ipertricosi, disabilità intellettiva lieve-grave, ritardo della crescita prenatale e/o postnatale, difficoltà di alimentazione, anomalie delle mani e dei piedi (difetti gravi in riduzione degli arti, oligodattilia, brachimetacarpia del primo metacarpo). I pazienti possono presentare anche malformazioni viscerali variabili."},"nl":{"name":"Syndroom van Cornelia de Lange","synonyms":["Syndroom van Brachmann-de Lange"],"definition":"Een zeldzaam syndroom met multipele congenitale anomalieën, gekenmerkt door faciale dysmorfie, hypertrichose, milde tot zeer ernstige intellectuele achterstand, intra-uteriene groeirestrictie (IUGR) en/of postnatale groeirestrictie, voedingsproblemen, afwijkingen van handen en voeten (gaande van ernstige reductiedefecten van ledematen en oligodactylie, tot brachymetacarpie van eerste metacarpus). Variabele viscerale malformaties kunnen aanwezig zijn."},"pt":{"name":"Síndrome Cornelia de Lange","synonyms":["Síndrome Brachman-de Lange"],"definition":"Uma síndrome rara de anomalias congénitas múltiplas caracterizada por dismorfismo facial, hipertricose, deficiência intelectual leve a profunda, restrição de crescimento intrauterino (RCIU) e/ou restrição de crescimento pós-natal, dificuldades de alimentação, anomalias nas mãos e pés (variando de anomalias de redução graves nos membros, oligodactilia, a braquimetacarpia do primeiro metacarpo). As malformações viscerais variáveis ​​podem estar presentes."},"pl":{"name":"Zespół Cornelii de Lange","synonyms":["Zespół Brachmanna i de Lange"],"definition":"Zespół Cornelii de Lange (Cornelia de Lange syndrome – CdLS) to wieloukładowe schorzenie ze zmienną ekspresją z charakterystyczną dysmorfią twarzy, niepełnosprawnością intelektualną o zmiennym nasileniu, zanacznym opóźnieniem wzrostu, które rozpoczyna się w okresie prenatalnym (drugi trymestr), nieprawidłowym wyglądem dłoni i stóp (oligodaktylia lub czasami nawet brakiem, ze stałą brachymetakarpią pierwszej kości śródręcza) oraz innymi wadami (serca, nerek itp.)."},"cs":{"name":"Syndrom Cornelie de Langové","synonyms":["Syndrom Brachmannův-de Langeové","Syndrom Brachmann-de Langeové"]},"uk":{"name":"Синдром Корнелії де Ланге","synonyms":["Синдром Брахмана-де-Ланге"],"definition":"A rare multiple congenital anomalies syndrome characterized by facial dysmorphism, hypertrichosis, mild to profound intellectual disability, intrauterine growth restriction (IUGR) and/or postnatal growth restriction, feeding difficulties, abnormalities of the hands and feet (ranging from severe reductional limb abnormalities, oligodactyly, to brachymetacarpia of the first metacarpus). Variable visceral malformations may be present."},"zh":{"name":"德朗热综合征","synonyms":["Brachmann-de Lange综合征"]},"tr":{"name":"Cornelia de Lange sendromu","synonyms":["Brachmann-de Lange sendromu"]}},"xrefs":[{"source":"OMIM","code":"122470","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"300590","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"300882","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"610759","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614701","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620568","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"621570","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.1","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"LD2F.1Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1801560012"},{"source":"MONDO","code":"0016033","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D003635","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0270972","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"10109","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10077707","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":404574,"name":"Genetic syndrome with limb reduction defects","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":138055,"name":"Pierre Robin syndrome associated with bone disease","classifications":[147,156,200,209]},{"orpha":98578,"name":"Rare disorder with ptosis","classifications":[147,156,189]},{"orpha":294955,"name":"Syndrome with limb reduction defects","classifications":[147,199]},{"orpha":108979,"name":"Syndromic diaphragmatic or abdominal wall malformation","classifications":[147,182]},{"orpha":180779,"name":"Syndromic diaphragmatic or thoracic malformation","classifications":[186]}],"children":[],"genes":[{"symbol":"HDAC8","name":"histone deacetylase 8","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"22885700[PMID]","hgnc":"13315","ensembl":"ENSG00000147099","omim":"300269","loci":["Xq13.1"]},{"symbol":"BRD4","name":"bromodomain containing 4","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"29379197[PMID]","hgnc":"13575","ensembl":"ENSG00000141867","omim":"608749","loci":["19p13.12"]},{"symbol":"MAU2","name":"MAU2 sister chromatid cohesion factor","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"32433956[PMID]_37962004[PMID]_41912533[PMID]","hgnc":"29140","ensembl":null,"omim":null,"loci":["19p13.11"]},{"symbol":"NIPBL","name":"NIPBL cohesin loading factor","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301283[PMID]","hgnc":"28862","ensembl":"ENSG00000164190","omim":"608667","loci":["5p13.2"]},{"symbol":"RAD21","name":"RAD21 cohesin complex component","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22633399[PMID]","hgnc":"9811","ensembl":"ENSG00000164754","omim":"606462","loci":["8q24.11"]},{"symbol":"SMC1A","name":"structural maintenance of chromosomes 1A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301283[PMID]","hgnc":"11111","ensembl":"ENSG00000072501","omim":"300040","loci":["Xp11.22"]},{"symbol":"SMC3","name":"structural maintenance of chromosomes 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301283[PMID]","hgnc":"2468","ensembl":"ENSG00000108055","omim":"606062","loci":["10q25.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant","Not applicable","X-linked recessive"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":1.24,"area":"Europe","status":"Validated","source":"18074387[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.65,"area":"France","status":"Validated","source":"22925539[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.5,"area":"Denmark","status":"Validated","source":"961413[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0010300","label":"Abnormally low-pitched voice","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000413","label":"Atresia of the external auditory canal","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000248","label":"Brachycephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007665","label":"Curly eyelashes","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000684","label":"Delayed eruption of teeth","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:0002714","label":"Downturned corners of mouth","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002230","label":"Generalized hirsutism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002553","label":"Highly arched eyebrow","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000527","label":"Long eyelashes","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000294","label":"Low anterior hairline","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002162","label":"Low posterior hairline","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002983","label":"Micromelia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0009623","label":"Proximal placement of thumb","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010034","label":"Short 1st metacarpal","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001773","label":"Short foot","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003196","label":"Short nose","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0200055","label":"Small hand","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000664","label":"Synophrys","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000574","label":"Thick eyebrow","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000233","label":"Thin vermilion border","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001770","label":"Toe syndactyly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000687","label":"Widely spaced teeth","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002167","label":"Abnormality of speech or vocalization","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000739","label":"Anxiety","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007018","label":"Attention deficit hyperactivity disorder","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007598","label":"Bilateral single transverse palmar creases","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000498","label":"Blepharitis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004209","label":"Clinodactyly of the 5th finger","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000722","label":"Compulsive behaviors","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000405","label":"Conductive hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000965","label":"Cutis marmorata","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003042","label":"Elbow dislocation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008736","label":"Hypoplasia of penis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000059","label":"Hypoplastic labia majora","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002557","label":"Hypoplastic nipples","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000047","label":"Hypospadias","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001387","label":"Joint stiffness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000482","label":"Microcornea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000003","label":"Multicystic kidney dysplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000667","label":"Phthisis bulbi","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001622","label":"Premature birth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002974","label":"Radioulnar synostosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008850","label":"Severe postnatal growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002360","label":"Sleep abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000076","label":"Vesicoureteral reflux","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030680","label":"Abnormal cardiovascular system morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0040071","label":"Abnormal morphology of ulna","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000130","label":"Abnormality of the uterus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007360","label":"Aplasia/Hypoplasia of the cerebellum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001631","label":"Atrial septal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000717","label":"Autism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000453","label":"Choanal atresia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000175","label":"Cleft palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000776","label":"Congenital diaphragmatic hernia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000823","label":"Delayed puberty","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000501","label":"Glaucoma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002827","label":"Hip dislocation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001385","label":"Hip dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010880","label":"Increased nuchal translucency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002566","label":"Intestinal malrotation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000400","label":"Macrotia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012165","label":"Oligodactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000767","label":"Pectus excavatum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009830","label":"Peripheral neuropathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001557","label":"Prenatal movement abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000786","label":"Primary amenorrhea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002021","label":"Pyloric stenosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000083","label":"Renal insufficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001883","label":"Talipes","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001956","label":"Truncal obesity","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},{"hpo":"HP:0002580","label":"Volvulus","frequency":"Occasional (29-5%)","criteria":null}]}}