CDLS4
MCID: CRN215
MIFTS: 28

Cornelia De Lange Syndrome 4 (CDLS4)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Smell/Taste diseases

Aliases & Classifications for Cornelia De Lange Syndrome 4

MalaCards integrated aliases for Cornelia De Lange Syndrome 4:

Name: Cornelia De Lange Syndrome 4 57 12 74 29 13 6 72
Cdls4 57 74
Cornelia De Lange Syndrome, Type 4 40

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
patients with contiguous gene deletion of 8q24 have more severe features
two patients with point mutations in rad21 have been reported (last curated july 2012)


HPO:

32
cornelia de lange syndrome 4:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0080508
MeSH 44 D003635
UMLS 72 C3553517

Summaries for Cornelia De Lange Syndrome 4

UniProtKB/Swiss-Prot : 74 Cornelia de Lange syndrome 4: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies.

MalaCards based summary : Cornelia De Lange Syndrome 4, also known as cdls4, is related to cornelia de lange syndrome 1 and trichorhinophalangeal syndrome, type ii. An important gene associated with Cornelia De Lange Syndrome 4 is RAD21 (RAD21 Cohesin Complex Component). Affiliated tissues include brain, and related phenotypes are gastroesophageal reflux and cleft palate

Disease Ontology : 12 A Cornelia de Lange syndrome that has material basis in heterozygous mutation in the RAD21 gene, which encodes a component of the cohesin complex, on chromosome 8q24.

More information from OMIM: 614701 PS122470

Related Diseases for Cornelia De Lange Syndrome 4

Diseases in the Cornelia De Lange Syndrome family:

Cornelia De Lange Syndrome 1 Cornelia De Lange Syndrome 2
Cornelia De Lange Syndrome 5 Cornelia De Lange Syndrome 3
Cornelia De Lange Syndrome 4

Diseases related to Cornelia De Lange Syndrome 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 cornelia de lange syndrome 1 10.3
2 trichorhinophalangeal syndrome, type ii 10.3
3 cornelia de lange syndrome 10.3
4 trichorhinophalangeal syndrome 10.3
5 exostoses, multiple, type i 10.2
6 trichorhinophalangeal syndrome, type i 10.2
7 hypotonia 10.2

Graphical network of the top 20 diseases related to Cornelia De Lange Syndrome 4:



Diseases related to Cornelia De Lange Syndrome 4

Symptoms & Phenotypes for Cornelia De Lange Syndrome 4

Human phenotypes related to Cornelia De Lange Syndrome 4:

32 (show all 18)
# Description HPO Frequency HPO Source Accession
1 gastroesophageal reflux 32 occasional (7.5%) HP:0002020
2 cleft palate 32 occasional (7.5%) HP:0000175
3 brachydactyly 32 occasional (7.5%) HP:0001156
4 hemivertebrae 32 occasional (7.5%) HP:0002937
5 cutis marmorata 32 occasional (7.5%) HP:0000965
6 syndactyly 32 occasional (7.5%) HP:0001159
7 vertebral clefting 32 occasional (7.5%) HP:0008428
8 global developmental delay 32 HP:0001263
9 wide nasal bridge 32 HP:0000431
10 microcephaly 32 HP:0000252
11 smooth philtrum 32 HP:0000319
12 thick eyebrow 32 HP:0000574
13 short stature 32 HP:0004322
14 long philtrum 32 HP:0000343
15 exostoses 32 HP:0100777
16 highly arched eyebrow 32 HP:0002553
17 thin upper lip vermilion 32 HP:0000219
18 synophrys 32 HP:0000664

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Nose:
wide nasal bridge
broad nasal bridge

Head And Neck Face:
smooth philtrum
long philtrum

Head And Neck Eyes:
synophrys
thick eyebrows
arched eyebrows
long lashes

Head And Neck Mouth:
thin upper lip
cleft palate (less common)

Abdomen Gastrointestinal:
gastroesophageal reflux (less common)

Skeletal Limbs:
exostoses (in patients with larger deletions involving the ext1 gene)
radioulnar abnormalities (in some patients)

Neurologic Central Nervous System:
cognitive delay, mild to severe

Head And Neck Head:
microcephaly

Growth Height:
short stature

Skin Nails Hair Hair:
synophrys
thick eyebrows
arched eyebrows
long lashes

Skeletal Hands:
brachydactyly (in some patients)
syndactyly (in some patients)

Skeletal Spine:
vertebral clefting (in some patients)
hemivertebrae (in some patients)

Skin Nails Hair Skin:
cutis marmorata (in some)

Clinical features from OMIM:

614701

Drugs & Therapeutics for Cornelia De Lange Syndrome 4

Search Clinical Trials , NIH Clinical Center for Cornelia De Lange Syndrome 4

Genetic Tests for Cornelia De Lange Syndrome 4

Genetic tests related to Cornelia De Lange Syndrome 4:

# Genetic test Affiliating Genes
1 Cornelia De Lange Syndrome 4 29 RAD21

Anatomical Context for Cornelia De Lange Syndrome 4

MalaCards organs/tissues related to Cornelia De Lange Syndrome 4:

41
Brain

Publications for Cornelia De Lange Syndrome 4

Articles related to Cornelia De Lange Syndrome 4:

# Title Authors PMID Year
1
RAD21 mutations cause a human cohesinopathy. 8 71
22633399 2012
2
Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. 71
23519317 2013
3
Further case of microdeletion of 8q24 with phenotype overlapping Langer-Giedion without TRPS1 deletion. 8
18478595 2008
4
Cornelia de Lange Syndrome 71
20301283 2005
5
Multiple exostoses, mental retardation, hypertrichosis, and brain abnormalities in a boy with a de novo 8q24 submicroscopic interstitial deletion. 8
12457403 2002
6
Prenatal diagnosis and array comparative genomic hybridization characterization of interstitial deletions of 8q23.3-q24.11 and 8q24.13 associated with Langer-Giedion syndrome, Cornelia de Lange syndrome and haploinsufficiency of TRPS1, RAD21 and EXT1. 38
26522117 2015
7
Cornelia de Lange syndrome caused by heterozygous deletions of chromosome 8q24: comments on the article by Pereza et al. [2012]. 38
25899858 2015
8
An interstitial deletion at 8q23.1-q24.12 associated with Langer-Giedion syndrome/ Trichorhinophalangeal syndrome (TRPS) type II and Cornelia de Lange syndrome 4. 38
26269715 2015
9
Erratum to: An interstitial deletion at 8q23.1-q24.12 associated with Langer-Giedion syndrome/ Trichorhinophalangeal syndrome (TRPS) type II and Cornelia de Lange syndrome 4. 38
26430469 2015
10
An interstitial deletion of 8q23.3-q24.22 associated with Langer-Giedion syndrome, Cornelia de Lange syndrome and epilepsy. 38
23933416 2013

Variations for Cornelia De Lange Syndrome 4

ClinVar genetic disease variations for Cornelia De Lange Syndrome 4:

6 (show all 23)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 RAD21 NM_006265.2(RAD21): c.181_182dup (p.Gly62fs) duplication Pathogenic rs1554612096 8:117875461-117875462 8:116863222-116863223
2 RAD21 NM_006265.2(RAD21): c.1550dup (p.Glu518fs) duplication Pathogenic 8:117862927-117862927 8:116850688-116850688
3 RAD21 NM_006265.2(RAD21): c.1161+1G> A single nucleotide variant Pathogenic 8:117866483-117866483 8:116854244-116854244
4 RAD21 NM_006265.2(RAD21): c.208A> T (p.Lys70Ter) single nucleotide variant Pathogenic rs1554612093 8:117875435-117875435 8:116863196-116863196
5 RAD21 NM_006265.2(RAD21): c.1127C> G (p.Pro376Arg) single nucleotide variant Pathogenic rs387907212 8:117866518-117866518 8:116854279-116854279
6 RAD21 NM_006265.2(RAD21): c.1753T> C (p.Cys585Arg) single nucleotide variant Pathogenic rs387907213 8:117859882-117859882 8:116847643-116847643
7 RAD21 NM_006265.2(RAD21): c.56_62del (p.Leu19fs) deletion Pathogenic rs797045907 8:117878907-117878913 8:116866668-116866674
8 RAD21 NM_006265.2(RAD21): c.579dup (p.Glu194fs) duplication Pathogenic rs797045908 8:117869615-117869615 8:116857376-116857376
9 RAD21 NM_006265.2(RAD21): c.590_591AG[3] (p.Ser198fs) short repeat Pathogenic rs797045909 8:117869601-117869602 8:116857362-116857363
10 RAD21 NM_006265.2(RAD21): c.1808T> C (p.Leu603Pro) single nucleotide variant Likely pathogenic rs863224910 8:117859827-117859827 8:116847588-116847588
11 RAD21 NM_006265.2(RAD21): c.1774_1776del (p.Gln592del) deletion Likely pathogenic 8:117859859-117859861 8:116847620-116847622
12 RAD21 NM_006265.2(RAD21): c.145-4A> G single nucleotide variant Conflicting interpretations of pathogenicity rs752213732 8:117875502-117875502 8:116863263-116863263
13 RAD21 NM_006265.2(RAD21): c.1782C> T (p.Ala594=) single nucleotide variant Uncertain significance rs61737172 8:117859853-117859853 8:116847614-116847614
14 RAD21 NM_006265.2(RAD21): c.1617A> G (p.Glu539=) single nucleotide variant Uncertain significance rs138040512 8:117862860-117862860 8:116850621-116850621
15 RAD21 NM_006265.2(RAD21): c.1852A> G (p.Ser618Gly) single nucleotide variant Uncertain significance rs1554610467 8:117859783-117859783 8:116847544-116847544
16 RAD21 NM_006265.2(RAD21): c.1352T> G (p.Leu451Arg) single nucleotide variant Uncertain significance rs144953114 8:117864305-117864305 8:116852066-116852066
17 RAD21 NM_006265.2(RAD21): c.1349G> A (p.Arg450His) single nucleotide variant Uncertain significance rs1051321465 8:117864308-117864308 8:116852069-116852069
18 RAD21 NM_006265.2(RAD21): c.1576G> C (p.Glu526Gln) single nucleotide variant Uncertain significance rs373026310 8:117862901-117862901 8:116850662-116850662
19 RAD21 NM_006265.2(RAD21): c.815-5delT deletion Likely benign rs35902828 8:117868532-117868532 8:116856293-116856293
20 RAD21 NM_006265.2(RAD21): c.1065G> A (p.Pro355=) single nucleotide variant Likely benign rs202233096 8:117866580-117866580 8:116854341-116854341
21 RAD21 NM_006265.2(RAD21): c.1848G> A (p.Pro616=) single nucleotide variant Likely benign rs761965871 8:117859787-117859787 8:116847548-116847548
22 RAD21 NM_006265.2(RAD21): c.786C> T (p.Asp262=) single nucleotide variant Benign rs34653007 8:117868913-117868913 8:116856674-116856674
23 RAD21 NM_006265.2(RAD21): c.1515C> G (p.Pro505=) single nucleotide variant Benign rs9297560 8:117862962-117862962 8:116850723-116850723

UniProtKB/Swiss-Prot genetic disease variations for Cornelia De Lange Syndrome 4:

74
# Symbol AA change Variation ID SNP ID
1 RAD21 p.Pro376Arg VAR_068691 rs387907212
2 RAD21 p.Cys585Arg VAR_068692 rs387907213

Expression for Cornelia De Lange Syndrome 4

Search GEO for disease gene expression data for Cornelia De Lange Syndrome 4.

Pathways for Cornelia De Lange Syndrome 4

GO Terms for Cornelia De Lange Syndrome 4

Sources for Cornelia De Lange Syndrome 4

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