CDLS5
MCID: CRN209
MIFTS: 40

Cornelia De Lange Syndrome 5 (CDLS5)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Muscle diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Cornelia De Lange Syndrome 5

MalaCards integrated aliases for Cornelia De Lange Syndrome 5:

Name: Cornelia De Lange Syndrome 5 57 11 73 28 5 14 71
Cdls5 57 73
Cornelia De Lange Syndrome, Type 5 38

Characteristics:


Inheritance:

X-linked dominant 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
variable severity
females may be unaffected or mildly affected


HPO:

30
cornelia de lange syndrome 5:
Onset and clinical course variable expressivity


Classifications:



Summaries for Cornelia De Lange Syndrome 5

OMIM®: 57 Cornelia de Lange syndrome is a clinically heterogeneous developmental disorder characterized by malformations affecting multiple systems. Affected individuals have dysmorphic facial features, cleft palate, distal limb defects, growth retardation, and developmental delay. About 60% of patients have mutations in the NIPBL gene (608667) on chromosome 5p13 (CDLS1; 122470), and about 4 to 6% of patients have mutations in the X-linked SMC1A gene (300040) (CDLS2; 300590) (summary by Musio et al., 2006, Hoppman-Chaney et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of Cornelia de Lange syndrome, see 122470. (300882) (Updated 08-Dec-2022)

MalaCards based summary: Cornelia De Lange Syndrome 5, also known as cdls5, is related to cornelia de lange syndrome and cornelia de lange syndrome 1. An important gene associated with Cornelia De Lange Syndrome 5 is HDAC8 (Histone Deacetylase 8), and among its related pathways/superpathways is Chromatin organization. Affiliated tissues include heart, testes and eye, and related phenotypes are hearing impairment and ptosis

UniProtKB/Swiss-Prot: 73 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.

Disease Ontology: 11 A Cornelia de Lange syndrome that has material basis in by mutation in the HDAC8 gene on chromosome Xq13.

Related Diseases for Cornelia De Lange Syndrome 5

Graphical network of the top 20 diseases related to Cornelia De Lange Syndrome 5:



Diseases related to Cornelia De Lange Syndrome 5

Symptoms & Phenotypes for Cornelia De Lange Syndrome 5

Human phenotypes related to Cornelia De Lange Syndrome 5:

30 (show all 49)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hearing impairment 30 Occasional (7.5%) HP:0000365
2 ptosis 30 Very rare (1%) HP:0000508
3 high palate 30 Very rare (1%) HP:0000218
4 global developmental delay 30 Very rare (1%) HP:0001263
5 anteverted nares 30 Very rare (1%) HP:0000463
6 feeding difficulties in infancy 30 Very rare (1%) HP:0008872
7 brachycephaly 30 Very rare (1%) HP:0000248
8 micrognathia 30 Very rare (1%) HP:0000347
9 downturned corners of mouth 30 Very rare (1%) HP:0002714
10 clinodactyly of the 5th finger 30 Very rare (1%) HP:0004209
11 highly arched eyebrow 30 Very rare (1%) HP:0002553
12 long philtrum 30 Very rare (1%) HP:0000343
13 ventriculomegaly 30 Very rare (1%) HP:0002119
14 low anterior hairline 30 Very rare (1%) HP:0000294
15 prominent nasal bridge 30 Very rare (1%) HP:0000426
16 small hand 30 Very rare (1%) HP:0200055
17 thin vermilion border 30 Very rare (1%) HP:0000233
18 proximal placement of thumb 30 Very rare (1%) HP:0009623
19 synophrys 30 Very rare (1%) HP:0000664
20 short foot 30 Very rare (1%) HP:0001773
21 cutis marmorata 30 Very rare (1%) HP:0000965
22 long eyelashes 30 Very rare (1%) HP:0000527
23 hirsutism 30 Very rare (1%) HP:0001007
24 limited elbow extension 30 Very rare (1%) HP:0001377
25 intellectual disability 30 HP:0001249
26 seizure 30 HP:0001250
27 short neck 30 HP:0000470
28 depressed nasal bridge 30 HP:0005280
29 hypertelorism 30 HP:0000316
30 widely spaced teeth 30 HP:0000687
31 microcephaly 30 HP:0000252
32 short stature 30 HP:0004322
33 gastroesophageal reflux 30 HP:0002020
34 cleft palate 30 HP:0000175
35 cryptorchidism 30 HP:0000028
36 postnatal growth retardation 30 HP:0008897
37 retrognathia 30 HP:0000278
38 myopia 30 HP:0000545
39 nevus 30 HP:0003764
40 micropenis 30 HP:0000054
41 deeply set eye 30 HP:0000490
42 telecanthus 30 HP:0000506
43 decreased testicular size 30 HP:0008734
44 toe syndactyly 30 HP:0001770
45 truncal obesity 30 HP:0001956
46 hypogonadism 30 HP:0000135
47 broad nasal tip 30 HP:0000455
48 generalized hypotonia 30 HP:0001290
49 happy demeanor 30 HP:0040082

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
intellectual disability
mental retardation (in males)
learning disabilities (in females)

Head And Neck Neck:
short neck

Head And Neck Nose:
depressed nasal bridge
broad nasal tip
anteverted nostrils
long columella

Abdomen Gastrointestinal:
gastroesophageal reflux
feeding problems

Head And Neck Mouth:
cleft palate
high-arched palate
downturned corners of the mouth

Head And Neck Face:
retrognathia
micrognathia
long philtrum

Skeletal Feet:
toe syndactyly
small feet

Neurologic Behavioral Psychiatric Manifestations:
happy demeanor
behavioral disorders

Head And Neck Ears:
hearing loss (in some patients)

Growth Height:
short stature (family h)

Genitourinary External Genitalia Male:
small penis (family h)

Endocrine Features:
hypogonadism (family h)

Head And Neck Eyes:
ptosis
hypertelorism
myopia
telecanthus
synophrys
more
Muscle Soft Tissue:
hypotonia

Head And Neck Teeth:
widely spaced teeth

Head And Neck Head:
brachycephaly
small head circumference

Growth Other:
postnatal growth retardation

Skin Nails Hair Hair:
low anterior hairline
hirsutism

Skin Nails Hair Skin:
cutis marmorata
nevus flammus

Skeletal Hands:
small hands

Skeletal Skull:
delayed closure of the fontanels

Growth Weight:
truncal obesity (family h)

Genitourinary Internal Genitalia Male:
small testes (family h)
cryptorchidism (family h)

Clinical features from OMIM®:

300882 (Updated 08-Dec-2022)

MGI Mouse Phenotypes related to Cornelia De Lange Syndrome 5:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 hearing/vestibular/ear MP:0005377 8.8 KAT6B NFIX TMTC4

Drugs & Therapeutics for Cornelia De Lange Syndrome 5

Search Clinical Trials, NIH Clinical Center for Cornelia De Lange Syndrome 5

Genetic Tests for Cornelia De Lange Syndrome 5

Genetic tests related to Cornelia De Lange Syndrome 5:

# Genetic test Affiliating Genes
1 Cornelia De Lange Syndrome 5 28 HDAC8

Anatomical Context for Cornelia De Lange Syndrome 5

Organs/tissues related to Cornelia De Lange Syndrome 5:

MalaCards : Heart, Testes, Eye, Brain
ODiseA: Brain, Heart-Atrium, Heart-Ventricle, Heart

Publications for Cornelia De Lange Syndrome 5

Articles related to Cornelia De Lange Syndrome 5:

(show all 23)
# Title Authors PMID Year
1
Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance. 57 5
24403048 2014
2
HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. 57 5
22885700 2012
3
X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face. 57 5
22889856 2012
4
Novel variant in HDAC8 gene resulting in the severe Cornelia de Lange phenotype. 62 57
30921088 2019
5
Clinical exome sequencing reveals locus heterogeneity and phenotypic variability of cohesinopathies. 5
30158690 2019
6
A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders. 5
26938784 2016
7
Molecular diagnostic experience of whole-exome sequencing in adult patients. 5
26633545 2016
8
Expanding the clinical spectrum of the 'HDAC8-phenotype' - implications for molecular diagnostics, counseling and risk prediction. 5
26671848 2016
9
Biochemical and structural characterization of HDAC8 mutants associated with Cornelia de Lange syndrome spectrum disorders. 5
26463496 2015
10
HDAC8-deficiency causes an X-linked dominant disorder with a wide range of severity. 57
25800122 2015
11
Cornelia de Lange syndrome. 57
25209348 2015
12
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 5
25741868 2015
13
Large-scale discovery of novel genetic causes of developmental disorders. 5
25533962 2015
14
Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes. 5
25574841 2015
15
Compromised structure and function of HDAC8 mutants identified in Cornelia de Lange Syndrome spectrum disorders. 5
25075551 2014
16
DIAMUND: direct comparison of genomes to detect mutations. 5
24375697 2014
17
In-frame multi-exon deletion of SMC1A in a severely affected female with Cornelia de Lange Syndrome. 57
22106055 2012
18
Epigenetic control of skull morphogenesis by histone deacetylase 8. 5
19605684 2009
19
X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations. 57
16604071 2006
20
Splicing in action: assessing disease causing sequence changes. 5
16199547 2005
21
Generation of an induced pluripotent stem cell line SJTUXHi001-A from an autism spectrum disorder patient carrying a heterozygous mutation in HDAC8 (p.P359S). 62
35358829 2022
22
[Clinical and genetic analysis of a neonate with Cornelia de Lange syndrome 5 caused by HDAC8 gene mutation]. 62
31302920 2019
23
Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation. 62
30632303 2019

Variations for Cornelia De Lange Syndrome 5

ClinVar genetic disease variations for Cornelia De Lange Syndrome 5:

5 (show top 50) (show all 113)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HDAC8 NM_018486.3(HDAC8):c.164+5G>A SNV Pathogenic
37252 rs398122888 GRCh37: X:71791902-71791902
GRCh38: X:72572052-72572052
2 overlap with 7 genes NC_000023.10:g.71681853_72434328del752476 DEL Pathogenic
209109 GRCh37: X:71681853-72434328
GRCh38:
3 HDAC8 NM_018486.3(HDAC8):c.104_105del (p.Pro35fs) DEL Pathogenic
545414 rs1556165162 GRCh37: X:71792507-71792508
GRCh38: X:72572657-72572658
4 HDAC8 NM_018486.3(HDAC8):c.787C>T (p.Gln263Ter) SNV Pathogenic
280671 rs886041838 GRCh37: X:71684532-71684532
GRCh38: X:72464682-72464682
5 HDAC8 NM_018486.3(HDAC8):c.738-1G>A SNV Pathogenic
804029 rs1602975601 GRCh37: X:71684582-71684582
GRCh38: X:72464732-72464732
6 HDAC8 NM_018486.3(HDAC8):c.1081C>T (p.Arg361Ter) SNV Pathogenic
433191 rs1555948969 GRCh37: X:71571613-71571613
GRCh38: X:72351763-72351763
7 HDAC8 NM_018486.3(HDAC8):c.522C>A (p.Tyr174Ter) SNV Pathogenic
446297 rs146015223 GRCh37: X:71715034-71715034
GRCh38: X:72495184-72495184
8 HDAC8 NM_018486.3(HDAC8):c.356C>G (p.Thr119Arg) SNV Pathogenic
987749 rs587779380 GRCh37: X:71787820-71787820
GRCh38: X:72567970-72567970
9 HDAC8 NM_018486.3(HDAC8):c.881G>A (p.Trp294Ter) SNV Pathogenic
1333326 GRCh37: X:71684438-71684438
GRCh38: X:72464588-72464588
10 HDAC8 NM_018486.3(HDAC8):c.1001A>G (p.His334Arg) SNV Pathogenic
39714 rs397515418 GRCh37: X:71681858-71681858
GRCh38: X:72462008-72462008
11 HDAC8 NM_018486.3(HDAC8):c.539A>G (p.His180Arg) SNV Pathogenic
39711 rs397515416 GRCh37: X:71715017-71715017
GRCh38: X:72495167-72495167
12 HDAC8 NM_018486.3(HDAC8):c.490C>T (p.Arg164Ter) SNV Pathogenic
39710 rs397515415 GRCh37: X:71715066-71715066
GRCh38: X:72495216-72495216
13 HDAC8 NM_018486.3(HDAC8):c.75_82del (p.Val25_Ser26insTer) DEL Pathogenic
1323053 GRCh37: X:71792530-71792537
GRCh38: X:72572680-72572687
14 HDAC8 NM_018486.3(HDAC8):c.471T>G (p.Asp157Glu) SNV Pathogenic
1164056 GRCh37: X:71715085-71715085
GRCh38: X:72495235-72495235
15 HDAC8 NM_018486.3(HDAC8):c.937C>T (p.Arg313Ter) SNV Pathogenic
523222 rs1569316085 GRCh37: X:71681922-71681922
GRCh38: X:72462072-72462072
16 HDAC8 NM_018486.3(HDAC8):c.131del (p.Ser43_Leu44insTer) DEL Pathogenic
158658 rs587783663 GRCh37: X:71791940-71791940
GRCh38: X:72572090-72572090
17 HDAC8 NM_018486.3(HDAC8):c.932C>T (p.Thr311Met) SNV Pathogenic
39712 rs397515417 GRCh37: X:71681927-71681927
GRCh38: X:72462077-72462077
18 overlap with 2 genes DEL Pathogenic
584437 GRCh37: X:71790521-71833766
GRCh38: X:72570671-72613916
19 HDAC8 NM_018486.3(HDAC8):c.229C>T (p.Gln77Ter) SNV Pathogenic
211141 rs797045611 GRCh37: X:71788670-71788670
GRCh38: X:72568820-72568820
20 HDAC8 NM_018486.3(HDAC8):c.295+2T>G SNV Pathogenic
844191 rs2051897517 GRCh37: X:71788602-71788602
GRCh38: X:72568752-72568752
21 HDAC8 NM_018486.3(HDAC8):c.164+2dup DUP Pathogenic
1072722 GRCh37: X:71791904-71791905
GRCh38: X:72572054-72572055
22 HDAC8 NM_018486.3(HDAC8):c.522C>G (p.Tyr174Ter) SNV Pathogenic
1076180 GRCh37: X:71715034-71715034
GRCh38: X:72495184-72495184
23 HDAC8 NM_018486.3(HDAC8):c.134_137del (p.Ile45fs) MICROSAT Pathogenic
211139 rs797045610 GRCh37: X:71791934-71791937
GRCh38: X:72572084-72572087
24 HDAC8 NM_018486.3(HDAC8):c.958G>A (p.Gly320Arg) SNV Pathogenic
39713 rs398122909 GRCh37: X:71681901-71681901
GRCh38: X:72462051-72462051
25 HDAC8 NM_018486.3(HDAC8):c.976_996del (p.Thr326_Pro332del) DEL Likely Pathogenic
1707472 GRCh37: X:71681863-71681883
GRCh38: X:72462013-72462033
26 HDAC8 NM_018486.3(HDAC8):c.839_843delinsGT (p.Thr280_Pro281delinsSer) INDEL Likely Pathogenic
369669 rs1057516037 GRCh37: X:71684476-71684480
GRCh38: X:72464626-72464630
27 HDAC8 NM_018486.3(HDAC8):c.556G>A (p.Glu186Lys) SNV Likely Pathogenic
211142 rs797045612 GRCh37: X:71710851-71710851
GRCh38: X:72491001-72491001
28 HDAC8 DEL Likely Pathogenic
1684651 GRCh37:
GRCh38: X:72456277-72483823
29 HDAC8 NC_000023.10:g.(?_71681834)_(71715138_?)dup DUP Likely Pathogenic
540333 GRCh37: X:71681834-71715138
GRCh38:
30 HDAC8 NM_018486.3(HDAC8):c.302A>G (p.Asp101Gly) SNV Likely Pathogenic
975708 rs2051867176 GRCh37: X:71787874-71787874
GRCh38: X:72568024-72568024
31 HDAC8 NM_018486.3(HDAC8):c.770C>A (p.Pro257His) SNV Likely Pathogenic
211143 rs797045613 GRCh37: X:71684549-71684549
GRCh38: X:72464699-72464699
32 HDAC8 NM_018486.3(HDAC8):c.1005+2T>C SNV Likely Pathogenic
1519914 GRCh37: X:71681852-71681852
GRCh38: X:72462002-72462002
33 HDAC8 NM_018486.3(HDAC8):c.551del (p.Gly184fs) DEL Likely Pathogenic
1333346 GRCh37: X:71710856-71710856
GRCh38: X:72491006-72491006
34 HDAC8 NM_018486.3(HDAC8):c.1019A>C (p.Tyr340Ser) SNV Likely Pathogenic
473110 rs1555949010 GRCh37: X:71571675-71571675
GRCh38: X:72351825-72351825
35 HDAC8 NM_018486.3(HDAC8):c.799G>A (p.Asp267Asn) SNV Likely Pathogenic
869426 rs2047965357 GRCh37: X:71684520-71684520
GRCh38: X:72464670-72464670
36 HDAC8 NM_018486.3(HDAC8):c.720T>G (p.Tyr240Ter) SNV Likely Pathogenic
928844 rs2048769063 GRCh37: X:71708800-71708800
GRCh38: X:72488950-72488950
37 HDAC8 NM_018486.3(HDAC8):c.584T>A (p.Val195Asp) SNV Likely Pathogenic
523220 rs1556009247 GRCh37: X:71710823-71710823
GRCh38: X:72490973-72490973
38 HDAC8 NM_018486.3(HDAC8):c.793G>A (p.Gly265Arg) SNV Likely Pathogenic
523221 rs1569318004 GRCh37: X:71684526-71684526
GRCh38: X:72464676-72464676
39 HDAC8 NM_018486.3(HDAC8):c.667C>T (p.Arg223Trp) SNV Likely Pathogenic
623138 rs1556007534 GRCh37: X:71708853-71708853
GRCh38: X:72489003-72489003
40 HDAC8 NM_018486.3(HDAC8):c.769C>T (p.Pro257Ser) SNV Likely Pathogenic
689725 rs1602975455 GRCh37: X:71684550-71684550
GRCh38: X:72464700-72464700
41 HDAC8 NM_018486.3(HDAC8):c.859T>C (p.Cys287Arg) SNV Likely Pathogenic
800965 rs1602975122 GRCh37: X:71684460-71684460
GRCh38: X:72464610-72464610
42 HDAC8 NM_018486.3(HDAC8):c.796G>C (p.Ala266Pro) SNV Likely Pathogenic
560685 rs1569317995 GRCh37: X:71684523-71684523
GRCh38: X:72464673-72464673
43 HDAC8 NM_018486.3(HDAC8):c.1006-2A>G SNV Likely Pathogenic
216939 rs863224877 GRCh37: X:71571690-71571690
GRCh38: X:72351840-72351840
44 HDAC8 NM_018486.3(HDAC8):c.737+1G>A SNV Likely Pathogenic
224074 rs869312660 GRCh37: X:71708782-71708782
GRCh38: X:72488932-72488932
45 HDAC8 NM_018486.3(HDAC8):c.527A>G (p.Asp176Gly) SNV Likely Pathogenic
374393 rs1057518727 GRCh37: X:71715029-71715029
GRCh38: X:72495179-72495179
46 HDAC8 NM_018486.3(HDAC8):c.356C>T (p.Thr119Met) SNV Conflicting Interpretations Of Pathogenicity
92043 rs587779380 GRCh37: X:71787820-71787820
GRCh38: X:72567970-72567970
47 HDAC8 NM_018486.3(HDAC8):c.22G>A (p.Ala8Thr) SNV Conflicting Interpretations Of Pathogenicity
931504 rs200093133 GRCh37: X:71792590-71792590
GRCh38: X:72572740-72572740
48 HDAC8 NM_018486.3(HDAC8):c.-5G>T SNV Uncertain Significance
158657 rs587783662 GRCh37: X:71792616-71792616
GRCh38: X:72572766-72572766
49 HDAC8 NM_018486.3(HDAC8):c.738-9969T>C SNV Uncertain Significance
1333188 GRCh37: X:71694550-71694550
GRCh38: X:72474700-72474700
50 HDAC8 NM_018486.3(HDAC8):c.24G>A (p.Ala8=) SNV Uncertain Significance
158660 rs61736843 GRCh37: X:71792588-71792588
GRCh38: X:72572738-72572738

UniProtKB/Swiss-Prot genetic disease variations for Cornelia De Lange Syndrome 5:

73
# Symbol AA change Variation ID SNP ID
1 HDAC8 p.His180Arg VAR_069140 rs397515416
2 HDAC8 p.Thr311Met VAR_069141 rs397515417
3 HDAC8 p.Gly320Arg VAR_069142 rs398122909
4 HDAC8 p.His334Arg VAR_069143 rs397515418

Expression for Cornelia De Lange Syndrome 5

Search GEO for disease gene expression data for Cornelia De Lange Syndrome 5.

Pathways for Cornelia De Lange Syndrome 5

Pathways related to Cornelia De Lange Syndrome 5 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.64 NSD1 KAT6B HDAC8

GO Terms for Cornelia De Lange Syndrome 5

Biological processes related to Cornelia De Lange Syndrome 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin organization GO:0006325 9.02 NSD1 KAT6B HDAC8
2 DNA-templated transcription elongation GO:0006354 8.96 NSD1 KAT6B

Molecular functions related to Cornelia De Lange Syndrome 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription coregulator activity GO:0003712 8.92 NSD1 KAT6B

Sources for Cornelia De Lange Syndrome 5

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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