CDLS3
MCID: CRN320
MIFTS: 36

Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects (CDLS3)

Categories: Genetic diseases, Neuronal diseases

Aliases & Classifications for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

MalaCards integrated aliases for Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects:

Name: Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects 56
Cornelia De Lange Syndrome 3 56 12 73 29 13 6 15
Cdls3 56 73
Cornelia De Lange Syndrome, Type 3 39

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
highly variable phenotype


HPO:

31
cornelia de lange syndrome 3 with or without midline brain defects:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

UniProtKB/Swiss-Prot : 73 Cornelia de Lange syndrome 3: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. Characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. Cornelia de Lange syndrome type 3 is a mild form with absence of major structural anomalies. The phenotype in some instances approaches that of apparently non-syndromic mental retardation.

MalaCards based summary : Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects, also known as cornelia de lange syndrome 3, is related to cornelia de lange syndrome and microcephalic osteodysplastic primordial dwarfism, type i. An important gene associated with Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects is SMC3 (Structural Maintenance Of Chromosomes 3). Affiliated tissues include brain and heart, and related phenotypes are hearing impairment and intellectual disability

Disease Ontology : 12 A Cornelia de Lange syndrome that has material basis in heterozygous mutation in the SMC3 gene on chromosome 10q25.2.

OMIM : 56 Cornelia de Lange syndrome is a multisystem developmental disorder characterized by distinctive facial dysmorphism, pre- and postnatal growth failure, delayed psychomotor development and impaired intellectual development, hypertrichosis, and sometimes distal limb malformations (summary by Gil-Rodriguez et al., 2015). For a phenotypic description and a discussion of genetic heterogeneity of Cornelia de Lange syndrome, see 122470. (610759)

Related Diseases for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

Graphical network of the top 20 diseases related to Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects:



Diseases related to Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects

Symptoms & Phenotypes for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

Human phenotypes related to Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects:

31 (show top 50) (show all 61)
# Description HPO Frequency HPO Source Accession
1 hearing impairment 31 very rare (1%) HP:0000365
2 intellectual disability 31 very rare (1%) HP:0001249
3 depressed nasal bridge 31 very rare (1%) HP:0005280
4 short neck 31 very rare (1%) HP:0000470
5 smooth philtrum 31 very rare (1%) HP:0000319
6 anteverted nares 31 very rare (1%) HP:0000463
7 thick eyebrow 31 very rare (1%) HP:0000574
8 gastroesophageal reflux 31 very rare (1%) HP:0002020
9 feeding difficulties in infancy 31 very rare (1%) HP:0008872
10 brachycephaly 31 very rare (1%) HP:0000248
11 frontal bossing 31 very rare (1%) HP:0002007
12 microdontia 31 very rare (1%) HP:0000691
13 cleft palate 31 very rare (1%) HP:0000175
14 flat face 31 very rare (1%) HP:0012368
15 cryptorchidism 31 very rare (1%) HP:0000028
16 high palate 31 very rare (1%) HP:0000218
17 micrognathia 31 very rare (1%) HP:0000347
18 ptosis 31 very rare (1%) HP:0000508
19 myopia 31 very rare (1%) HP:0000545
20 atrial septal defect 31 very rare (1%) HP:0001631
21 bicuspid aortic valve 31 very rare (1%) HP:0001647
22 limited elbow movement 31 very rare (1%) HP:0002996
23 downturned corners of mouth 31 very rare (1%) HP:0002714
24 clinodactyly of the 5th finger 31 very rare (1%) HP:0004209
25 facial asymmetry 31 very rare (1%) HP:0000324
26 patent ductus arteriosus 31 very rare (1%) HP:0001643
27 highly arched eyebrow 31 very rare (1%) HP:0002553
28 thin upper lip vermilion 31 very rare (1%) HP:0000219
29 long philtrum 31 very rare (1%) HP:0000343
30 low anterior hairline 31 very rare (1%) HP:0000294
31 bulbous nose 31 very rare (1%) HP:0000414
32 ventricular septal defect 31 very rare (1%) HP:0001629
33 nevus flammeus 31 very rare (1%) HP:0001052
34 nasolacrimal duct obstruction 31 very rare (1%) HP:0000579
35 small hand 31 very rare (1%) HP:0200055
36 proximal placement of thumb 31 very rare (1%) HP:0009623
37 toe syndactyly 31 very rare (1%) HP:0001770
38 synophrys 31 very rare (1%) HP:0000664
39 plagiocephaly 31 very rare (1%) HP:0001357
40 hydroureter 31 very rare (1%) HP:0000072
41 short foot 31 very rare (1%) HP:0001773
42 cutis marmorata 31 very rare (1%) HP:0000965
43 long eyelashes 31 very rare (1%) HP:0000527
44 single transverse palmar crease 31 very rare (1%) HP:0000954
45 posteriorly rotated ears 31 very rare (1%) HP:0000358
46 postnatal microcephaly 31 very rare (1%) HP:0005484
47 hirsutism 31 very rare (1%) HP:0001007
48 short 5th finger 31 very rare (1%) HP:0009237
49 delayed closure of the anterior fontanelle 31 very rare (1%) HP:0001476
50 hooded eyelid 31 very rare (1%) HP:0030820

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
microcephaly
brachycephaly

Skeletal Limbs:
limited elbow movement

Head And Neck Eyes:
synophrys
long eyelashes
thick eyebrows
arched eyebrows
ptosis (in some patients)

Head And Neck Mouth:
thin upper lip
downturned corners of the mouth
high-arched palate (in some patients)

Cardiovascular Heart:
pulmonary valve stenosis
septal defects
congenital heart defects

Head And Neck Face:
long, smooth philtrum
micrognathia (in some patients)

Abdomen Gastrointestinal:
gastroesophageal reflux disease

Skin Nails Hair Skin:
cutis marmorata (in some patients)

Neurologic Central Nervous System:
cognitive impairment
poor speech
delayed psychomotor development

Skeletal Hands:
brachydactyly
small hands

Skin Nails Hair Hair:
thick hair
hirsutism
low anterior hairline (in some patients)

Head And Neck Nose:
anteverted nostrils
bulbous nasal tip
depressed nasal bridge (in some patients)

Head And Neck Neck:
short neck (in some patients)

Skeletal Feet:
small feet

Head And Neck Teeth:
dental anomalies (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
social demeanor

Clinical features from OMIM:

610759

Drugs & Therapeutics for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

Search Clinical Trials , NIH Clinical Center for Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects

Genetic Tests for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

Genetic tests related to Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects:

# Genetic test Affiliating Genes
1 Cornelia De Lange Syndrome 3 29 SMC3

Anatomical Context for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

MalaCards organs/tissues related to Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects:

40
Brain, Heart

Publications for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

Articles related to Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects:

# Title Authors PMID Year
1
Cohesin complex-associated holoprosencephaly. 6 56
31334757 2019
2
De novo heterozygous mutations in SMC3 cause a range of Cornelia de Lange syndrome-overlapping phenotypes. 56 6
25655089 2015
3
Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism. 6 56
25125236 2014
4
Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. 6 56
17273969 2007
5
Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. 6
23519317 2013
6
Cornelia de Lange syndrome mutations in SMC1A or SMC3 affect binding to DNA. 6
18996922 2009
7
Cornelia de Lange Syndrome 6
20301283 2005

Variations for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

ClinVar genetic disease variations for Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects:

6 (show top 50) (show all 108) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SMC3 NM_005445.3(SMC3):c.1067_1070AGAA[1] (p.Glu358fs)short repeat Pathogenic 626275 10:112343696-112343699 10:110583938-110583941
2 SMC3 NM_005445.4(SMC3):c.1138_1152del (p.Gly380_Gln384del)deletion Pathogenic 864833 10:112343984-112343998 10:110584226-110584240
3 SMC3 NM_005445.3(SMC3):c.1461_1463AGA[1] (p.Glu488del)short repeat Pathogenic 4631 rs863223279 10:112349701-112349703 10:110589943-110589945
4 SMC3 NM_005445.3(SMC3):c.2536-5_2541deldeletion Pathogenic 180199 rs727503775 10:112360774-112360784 10:110601016-110601026
5 SMC3 NM_005445.3(SMC3):c.2750A>C (p.His917Pro)SNV Pathogenic 208656 rs797044861 10:112361500-112361500 10:110601742-110601742
6 SMC3 NM_005445.3(SMC3):c.139T>C (p.Phe47Leu)SNV Pathogenic 217799 rs863225258 10:112335102-112335102 10:110575344-110575344
7 SMC3 NM_005445.3(SMC3):c.703_705del (p.Thr235del)deletion Pathogenic 217800 rs863225259 10:112341836-112341838 10:110582078-110582080
8 SMC3 NM_005445.3(SMC3):c.1462G>A (p.Glu488Lys)SNV Pathogenic 217802 rs863225260 10:112349702-112349702 10:110589944-110589944
9 SMC3 NM_005445.3(SMC3):c.1997G>C (p.Gly666Ala)SNV Pathogenic 217804 rs863225261 10:112356189-112356189 10:110596431-110596431
10 SMC3 NM_005445.3(SMC3):c.283G>A (p.Glu95Lys)SNV Likely pathogenic 224089 rs869312672 10:112337605-112337605 10:110577847-110577847
11 SMC3 NM_005445.3(SMC3):c.587T>C (p.Ile196Thr)SNV Likely pathogenic 209193 rs797045070 10:112341720-112341720 10:110581962-110581962
12 SMC3 NM_005445.3(SMC3):c.856_858GAA[3] (p.Glu287dup)short repeat Likely pathogenic 212273 rs797045997 10:112343190-112343191 10:110583432-110583433
13 SMC3 NM_005445.3(SMC3):c.2636G>C (p.Arg879Pro)SNV Likely pathogenic 212272 rs797045996 10:112360880-112360880 10:110601122-110601122
14 SMC3 NM_005445.3(SMC3):c.707G>C (p.Arg236Pro)SNV Likely pathogenic 159990 rs587784429 10:112341840-112341840 10:110582082-110582082
15 SMC3 NM_005445.4(SMC3):c.932A>G (p.Asp311Gly)SNV Likely pathogenic 802634 10:112343269-112343269 10:110583511-110583511
16 SMC3 NM_005445.4(SMC3):c.2952_2954del (p.Lys985del)deletion Likely pathogenic 827780 10:112361781-112361783 10:110602023-110602025
17 SMC3 NM_005445.3(SMC3):c.1964G>A (p.Gly655Asp)SNV Likely pathogenic 159970 rs587784425 10:112356156-112356156 10:110596398-110596398
18 SMC3 NM_005445.3(SMC3):c.2338G>C (p.Glu780Gln)SNV Likely pathogenic 159976 rs587784427 10:112359481-112359481 10:110599723-110599723
19 SMC3 NM_005445.3(SMC3):c.181C>T (p.Arg61Trp)SNV Likely pathogenic 620076 rs866273473 10:112335144-112335144 10:110575386-110575386
20 SMC3 NM_005445.3(SMC3):c.2005T>G (p.Tyr669Asp)SNV Likely pathogenic 436822 rs776056911 10:112356197-112356197 10:110596439-110596439
21 SMC3 NM_005445.3(SMC3):c.3373C>G (p.Leu1125Val)SNV Likely pathogenic 436823 rs901512521 10:112362658-112362658 10:110602900-110602900
22 SMC3 NM_005445.3(SMC3):c.1450_1452GCT[1] (p.Ala485del)short repeat Likely pathogenic 523214 rs1564792181 10:112349689-112349691 10:110589931-110589933
23 SMC3 NM_005445.3(SMC3):c.2111T>C (p.Ile704Thr)SNV Likely pathogenic 523215 rs1564794233 10:112356303-112356303 10:110596545-110596545
24 SMC3 NM_005445.3(SMC3):c.3362C>T (p.Ser1121Phe)SNV Likely pathogenic 523216 rs1564796294 10:112362647-112362647 10:110602889-110602889
25 SMC3 NM_005445.3(SMC3):c.2329T>C (p.Leu777=)SNV Conflicting interpretations of pathogenicity 159975 rs76625999 10:112359472-112359472 10:110599714-110599714
26 SMC3 NM_005445.3(SMC3):c.2493T>C (p.Tyr831=)SNV Conflicting interpretations of pathogenicity 159978 rs112525060 10:112360262-112360262 10:110600504-110600504
27 SMC3 NM_005445.3(SMC3):c.2535+15T>GSNV Conflicting interpretations of pathogenicity 159979 rs3818903 10:112360319-112360319 10:110600561-110600561
28 SMC3 NM_005445.3(SMC3):c.2934G>A (p.Lys978=)SNV Conflicting interpretations of pathogenicity 159983 rs147463420 10:112361765-112361765 10:110602007-110602007
29 SMC3 NM_005445.3(SMC3):c.2268+4C>TSNV Conflicting interpretations of pathogenicity 159973 rs587784426 10:112358052-112358052 10:110598294-110598294
30 SMC3 NM_005445.3(SMC3):c.1280A>G (p.Lys427Arg)SNV Conflicting interpretations of pathogenicity 159966 rs142524280 10:112344129-112344129 10:110584371-110584371
31 SMC3 NM_005445.3(SMC3):c.1581T>C (p.His527=)SNV Conflicting interpretations of pathogenicity 159968 rs182445355 10:112350241-112350241 10:110590483-110590483
32 SMC3 NM_005445.3(SMC3):c.1680T>C (p.Tyr560=)SNV Conflicting interpretations of pathogenicity 159969 rs75817442 10:112350758-112350758 10:110591000-110591000
33 SMC3 NM_005445.3(SMC3):c.255A>G (p.Ser85=)SNV Conflicting interpretations of pathogenicity 159980 rs146433240 10:112337235-112337235 10:110577477-110577477
34 SMC3 NM_005445.3(SMC3):c.377A>G (p.Glu126Gly)SNV Uncertain significance 159987 rs113411202 10:112338412-112338412 10:110578654-110578654
35 SMC3 NM_005445.3(SMC3):c.507C>T (p.Asp169=)SNV Uncertain significance 159988 rs370909218 10:112340739-112340739 10:110580981-110580981
36 SMC3 NM_005445.4(SMC3):c.3488A>G (p.Glu1163Gly)SNV Uncertain significance 841624 10:112362954-112362954 10:110603196-110603196
37 SMC3 NM_005445.4(SMC3):c.3147T>C (p.Pro1049=)SNV Uncertain significance 879043 10:112362273-112362273 10:110602515-110602515
38 SMC3 NM_005445.4(SMC3):c.3101A>G (p.Lys1034Arg)SNV Uncertain significance 816880 10:112361932-112361932 10:110602174-110602174
39 SMC3 NM_005445.4(SMC3):c.2892+9T>CSNV Uncertain significance 878459 10:112361651-112361651 10:110601893-110601893
40 SMC3 NM_005445.3(SMC3):c.2299T>C (p.Leu767=)SNV Uncertain significance 159974 rs139763232 10:112359442-112359442 10:110599684-110599684
41 SMC3 NM_005445.3(SMC3):c.2964T>C (p.Asp988=)SNV Uncertain significance 159984 rs111611128 10:112361795-112361795 10:110602037-110602037
42 SMC3 NM_005445.3(SMC3):c.2264C>T (p.Pro755Leu)SNV Uncertain significance 159972 rs76568464 10:112358044-112358044 10:110598286-110598286
43 SMC3 NM_005445.3(SMC3):c.2427+13C>TSNV Uncertain significance 159977 rs190798929 10:112359583-112359583 10:110599825-110599825
44 SMC3 NM_005445.3(SMC3):c.3400T>C (p.Cys1134Arg)SNV Uncertain significance 534189 rs1554884207 10:112362685-112362685 10:110602927-110602927
45 SMC3 NM_005445.3(SMC3):c.661C>T (p.Arg221Ter)SNV Uncertain significance 581922 rs1564789897 10:112341794-112341794 10:110582036-110582036
46 SMC3 NM_005445.3(SMC3):c.1451C>G (p.Ala484Gly)SNV Uncertain significance 465777 rs758758728 10:112349691-112349691 10:110589933-110589933
47 SMC3 NM_005445.3(SMC3):c.424G>A (p.Gly142Arg)SNV Uncertain significance 465778 rs1554882316 10:112338459-112338459 10:110578701-110578701
48 SMC3 NM_005445.3(SMC3):c.125T>C (p.Phe42Ser)SNV Uncertain significance 465776 rs1554881901 10:112333498-112333498 10:110573740-110573740
49 SMC3 NM_005445.3(SMC3):c.371T>G (p.Leu124Arg)SNV Uncertain significance 638053 10:112338406-112338406 10:110578648-110578648
50 SMC3 NM_005445.3(SMC3):c.2132T>C (p.Ile711Thr)SNV Uncertain significance 638160 10:112357912-112357912 10:110598154-110598154

Expression for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

Search GEO for disease gene expression data for Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects.

Pathways for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

GO Terms for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

Biological processes related to Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mRNA 5'-splice site recognition GO:0000395 8.96 RNU6ATAC RNU4ATAC
2 spliceosomal tri-snRNP complex assembly GO:0000244 8.62 RNU6ATAC RNU4ATAC

Molecular functions related to Cornelia De Lange Syndrome 3 with or Without Midline Brain Defects according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 pre-mRNA 5'-splice site binding GO:0030627 8.62 RNU6ATAC RNU4ATAC

Sources for Cornelia De Lange Syndrome 3 with or Without Midline Brain...

3 CDC
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11 DGIdb
17 EFO
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57 OMIM via Orphanet
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68 SNOMED-CT via HPO
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