ORPHA:199
Cornelia de Lange syndrome
Synonyms: Brachmann-de Lange syndrome
- Type
- Malformation syndrome
- Group
- Disorder
- Inheritance
- Autosomal dominant, Not applicable, X-linked recessive
- Age of onset
- Antenatal, Neonatal
- Status
- active
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.
1
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Cornelia de Lange syndrome | Brachmann-de Lange syndrome |
| fr | Syndrome de Cornelia de Lange | Syndrome de Brachmann-de Lange |
| de | Cornelia de Lange-Syndrom | Brachmann-de Lange-Syndrom |
| es | Síndrome de Cornelia de Lange | |
| it | Sindrome di Cornelia de Lange | Sindrome di Brachmann-de Lange |
| nl | Syndroom van Cornelia de Lange | Syndroom van Brachmann-de Lange |
| pt | Síndrome Cornelia de Lange | Síndrome Brachman-de Lange |
| pl | Zespół Cornelii de Lange | Zespół Brachmanna i de Lange |
| cs | Syndrom Cornelie de Langové | Syndrom Brachmannův-de Langeové · Syndrom Brachmann-de Langeové |
| uk | Синдром Корнелії де Ланге | Синдром Брахмана-де-Ланге |
| zh | 德朗热综合征 | Brachmann-de Lange综合征 |
| tr | Cornelia de Lange sendromu | Brachmann-de Lange sendromu |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 122470 | E | validated | |
| OMIM | 300590 | BTNT | validated | |
| OMIM | 300882 | BTNT | validated | |
| OMIM | 610759 | BTNT | validated | |
| OMIM | 614701 | BTNT | validated | |
| OMIM | 620568 | BTNT | validated | |
| OMIM | 621570 | BTNT | validated | |
| ICD-10 | Q87.1 | NTBT | inclusion | validated |
| ICD-11 | LD2F.1Y | NTBT | index | validated |
| MONDO | 0016033 | E | validated | |
| MeSH | D003635 | E | validated | |
| UMLS | C0270972 | E | validated | |
| GARD | 10109 | E | validated | |
| MedDRA | 10077707 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
3
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (10):
- ORPHA:183570Genetic malformation syndrome with short stature
rare genetic diseases - ORPHA:611327Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare genetic diseases - ORPHA:404574Genetic syndrome with limb reduction defects
rare genetic diseases - ORPHA:139021Malformation syndrome with short stature
rare developmental anomalies during embryogenesis - ORPHA:102283Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare developmental anomalies during embryogenesis; rare neurological diseases - ORPHA:138055Pierre Robin syndrome associated with bone disease
rare developmental anomalies during embryogenesis; rare genetic diseases; rare otorhinolaryngological diseases; rare surgical maxillo-facial diseases - ORPHA:98578Rare disorder with ptosis
rare developmental anomalies during embryogenesis; rare genetic diseases; rare ophthalmic disorders - ORPHA:294955Syndrome with limb reduction defects
rare developmental anomalies during embryogenesis; rare bone diseases - ORPHA:108979Syndromic diaphragmatic or abdominal wall malformation
rare developmental anomalies during embryogenesis; rare abdominal surgical diseases - ORPHA:180779Syndromic diaphragmatic or thoracic malformation
rare surgical thoracic diseases
No children.
4
Genes
7 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| HDAC8 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:13315 | ENSG00000147099 | 300269 | Xq13.1 | histone deacetylase 8 | 22885700[PMID] |
| BRD4 | Disease-causing germline mutation(s) in | Assessed | HGNC:13575 | ENSG00000141867 | 608749 | 19p13.12 | bromodomain containing 4 | 29379197[PMID] |
| MAU2 | Disease-causing germline mutation(s) in | Assessed | HGNC:29140 | 19p13.11 | MAU2 sister chromatid cohesion factor | 32433956[PMID]_37962004[PMID]_41912533[PMID] | ||
| NIPBL | Disease-causing germline mutation(s) in | Assessed | HGNC:28862 | ENSG00000164190 | 608667 | 5p13.2 | NIPBL cohesin loading factor | 20301283[PMID] |
| RAD21 | Disease-causing germline mutation(s) in | Assessed | HGNC:9811 | ENSG00000164754 | 606462 | 8q24.11 | RAD21 cohesin complex component | 22633399[PMID] |
| SMC1A | Disease-causing germline mutation(s) in | Assessed | HGNC:11111 | ENSG00000072501 | 300040 | Xp11.22 | structural maintenance of chromosomes 1A | 20301283[PMID] |
| SMC3 | Disease-causing germline mutation(s) in | Assessed | HGNC:2468 | ENSG00000108055 | 606062 | 10q25.2 | structural maintenance of chromosomes 3 | 20301283[PMID] |
5
Prevalence and incidence
3 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Prevalence at birth | 1-9 / 100 000 | 1.24 / 100 000 | Europe | Value and class | Validated | 18074387[PMID] |
| Prevalence at birth | 1-9 / 1 000 000 | 0.65 / 100 000 | France | Value and class | Validated | 22925539[PMID] |
| Point prevalence | 1-9 / 1 000 000 | 0.5 / 100 000 | Denmark | Value and class | Validated | 961413[PMID] |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
6
HPO phenotypes
100 annotations · validated 2016-06-01| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0010300 | Abnormally low-pitched voice | |
| HP:0000463 | Anteverted nares | |
| HP:0000413 | Atresia of the external auditory canal | |
| HP:0000248 | Brachycephaly | |
| HP:0007665 | Curly eyelashes | |
| HP:0000684 | Delayed eruption of teeth | |
| HP:0002750 | Delayed skeletal maturation | |
| HP:0005280 | Depressed nasal bridge | |
| HP:0002714 | Downturned corners of mouth | |
| HP:0002020 | Gastroesophageal reflux | |
| HP:0002230 | Generalized hirsutism | |
| HP:0000218 | High palate | |
| HP:0002553 | Highly arched eyebrow | |
| HP:0001276 | Hypertonia | |
| HP:0001249 | Intellectual disability | |
| HP:0010864 | Intellectual disability, severe | |
| HP:0000527 | Long eyelashes | |
| HP:0000343 | Long philtrum | |
| HP:0000294 | Low anterior hairline | |
| HP:0002162 | Low posterior hairline | |
| HP:0000252 | Microcephaly | |
| HP:0000347 | Micrognathia | |
| HP:0002983 | Micromelia | |
| HP:0009623 | Proximal placement of thumb | |
| HP:0010034 | Short 1st metacarpal | |
| HP:0001773 | Short foot | |
| HP:0000470 | Short neck | |
| HP:0003196 | Short nose | |
| HP:0004322 | Short stature | |
| HP:0200055 | Small hand | |
| HP:0000664 | Synophrys | |
| HP:0000574 | Thick eyebrow | |
| HP:0000233 | Thin vermilion border | |
| HP:0001770 | Toe syndactyly | |
| HP:0000687 | Widely spaced teeth | |
| Frequent (79-30%) | ||
| HP:0002167 | Abnormality of speech or vocalization | |
| HP:0000739 | Anxiety | |
| HP:0007018 | Attention deficit hyperactivity disorder | |
| HP:0007598 | Bilateral single transverse palmar creases | |
| HP:0000498 | Blepharitis | |
| HP:0004209 | Clinodactyly of the 5th finger | |
| HP:0000722 | Compulsive behaviors | |
| HP:0000405 | Conductive hearing impairment | |
| HP:0000028 | Cryptorchidism | |
| HP:0000965 | Cutis marmorata | |
| HP:0003042 | Elbow dislocation | |
| HP:0001508 | Failure to thrive | |
| HP:0008872 | Feeding difficulties in infancy | |
| HP:0008736 | Hypoplasia of penis | |
| HP:0000059 | Hypoplastic labia majora | |
| HP:0002557 | Hypoplastic nipples | |
| HP:0000047 | Hypospadias | |
| HP:0001511 | Intrauterine growth retardation | |
| HP:0001387 | Joint stiffness | |
| HP:0000482 | Microcornea | |
| HP:0000003 | Multicystic kidney dysplasia | |
| HP:0000545 | Myopia | |
| HP:0000667 | Phthisis bulbi | |
| HP:0000358 | Posteriorly rotated ears | |
| HP:0001622 | Premature birth | |
| HP:0000508 | Ptosis | |
| HP:0002974 | Radioulnar synostosis | |
| HP:0000407 | Sensorineural hearing impairment | |
| HP:0008850 | Severe postnatal growth retardation | |
| HP:0002360 | Sleep abnormality | |
| HP:0000076 | Vesicoureteral reflux | |
| Occasional (29-5%) | ||
| HP:0030680 | Abnormal cardiovascular system morphology | |
| HP:0040071 | Abnormal morphology of ulna | |
| HP:0000130 | Abnormality of the uterus | |
| HP:0007360 | Aplasia/Hypoplasia of the cerebellum | |
| HP:0001631 | Atrial septal defect | |
| HP:0000717 | Autism | |
| HP:0000518 | Cataract | |
| HP:0002120 | Cerebral cortical atrophy | |
| HP:0000453 | Choanal atresia | |
| HP:0000175 | Cleft palate | |
| HP:0000776 | Congenital diaphragmatic hernia | |
| HP:0000823 | Delayed puberty | |
| HP:0000501 | Glaucoma | |
| HP:0002827 | Hip dislocation | |
| HP:0001385 | Hip dysplasia | |
| HP:0001252 | Hypotonia | |
| HP:0010880 | Increased nuchal translucency | |
| HP:0002566 | Intestinal malrotation | |
| HP:0000400 | Macrotia | |
| HP:0000639 | Nystagmus | |
| HP:0012165 | Oligodactyly | |
| HP:0000767 | Pectus excavatum | |
| HP:0009830 | Peripheral neuropathy | |
| HP:0001557 | Prenatal movement abnormality | |
| HP:0000786 | Primary amenorrhea | |
| HP:0002021 | Pyloric stenosis | |
| HP:0000083 | Renal insufficiency | |
| HP:0001250 | Seizure | |
| HP:0000486 | Strabismus | |
| HP:0001883 | Talipes | |
| HP:0001956 | Truncal obesity | |
| HP:0001629 | Ventricular septal defect | |
| HP:0002119 | Ventriculomegaly | |
| HP:0002580 | Volvulus | |
Run the differential on the 12 obligate / very frequent terms
7
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/199
- This record as JSON: /data/d/199.json