CSS4
MCID: CFF009
MIFTS: 40

Coffin-Siris Syndrome 4 (CSS4)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Coffin-Siris Syndrome 4

MalaCards integrated aliases for Coffin-Siris Syndrome 4:

Name: Coffin-Siris Syndrome 4 58 12 76 15
Mental Retardation, Autosomal Dominant 16 58 76 30 13 6 74
Mrd16 58 12 76
Css4 58 12 76
Mental Retardation, Autosomal Dominant 16; Mrd16 58
Autosomal Dominant Mental Retardation 16 12
Coffin-Siris Syndrome, Type 4 ) 41

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant


HPO:

33
coffin-siris syndrome 4:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Coffin-Siris Syndrome 4

UniProtKB/Swiss-Prot : 76 Coffin-Siris syndrome 4: A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported.

MalaCards based summary : Coffin-Siris Syndrome 4, also known as mental retardation, autosomal dominant 16, is related to neonatal period electroclinical syndrome and benign familial infantile epilepsy. An important gene associated with Coffin-Siris Syndrome 4 is SMARCA4 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 4), and among its related pathways/superpathways are Activation of cAMP-Dependent PKA and Developmental Biology. Affiliated tissues include bone and heart, and related phenotypes are seizures and microcephaly

Disease Ontology : 12 A Coffin-Siris syndrome that has material basis in an autosomal dominant mutation of SMARCA4 on chromosome 19p13.2.

OMIM : 58 Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Other more variable features may also occur. Patients with SMARCA4 mutations may have less coarse craniofacial appearances and fewer behavioral abnormalities than Coffin-Siris patients with mutations in other genes (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900). (614609)

Related Diseases for Coffin-Siris Syndrome 4

Graphical network of the top 20 diseases related to Coffin-Siris Syndrome 4:



Diseases related to Coffin-Siris Syndrome 4

Symptoms & Phenotypes for Coffin-Siris Syndrome 4

Human phenotypes related to Coffin-Siris Syndrome 4:

33 (show all 28)
# Description HPO Frequency HPO Source Accession
1 seizures 33 very rare (1%) HP:0001250
2 microcephaly 33 very rare (1%) HP:0000252
3 visual impairment 33 very rare (1%) HP:0000505
4 thick eyebrow 33 very rare (1%) HP:0000574
5 sparse scalp hair 33 very rare (1%) HP:0002209
6 long eyelashes 33 very rare (1%) HP:0000527
7 dandy-walker malformation 33 very rare (1%) HP:0001305
8 hirsutism 33 very rare (1%) HP:0001007
9 intellectual disability 33 HP:0001249
10 scoliosis 33 HP:0002650
11 macroglossia 33 HP:0000158
12 coarse facial features 33 HP:0000280
13 hearing impairment 33 HP:0000365
14 global developmental delay 33 HP:0001263
15 delayed skeletal maturation 33 HP:0002750
16 depressed nasal bridge 33 HP:0005280
17 anteverted nares 33 HP:0000463
18 short stature 33 HP:0004322
19 feeding difficulties 33 HP:0011968
20 thick nasal alae 33 HP:0009928
21 intrauterine growth retardation 33 HP:0001511
22 wide mouth 33 HP:0000154
23 wide nose 33 HP:0000445
24 generalized hypotonia 33 HP:0001290
25 abnormality of cardiovascular system morphology 33 HP:0030680
26 hypertrichosis 33 HP:0000998
27 aplasia/hypoplasia of the distal phalanges of the hand 33 HP:0009835
28 abnormal corpus callosum morphology 33 HP:0001273

Symptoms via clinical synopsis from OMIM:

58
Skeletal Spine:
scoliosis

Head And Neck Ears:
hearing impairment

Growth Height:
short stature

Growth Other:
intrauterine growth retardation
poor overall growth

Neurologic Central Nervous System:
hypotonia
mental retardation
delayed psychomotor development
abnormal corpus callosum
absence of speech

Head And Neck Face:
coarse facies

Head And Neck Teeth:
delayed dentition

Skeletal Hands:
hypoplastic to absent terminal phalanges (especially fifth finger)

Head And Neck Head:
microcephaly (in some patients)

Head And Neck Mouth:
macroglossia
large mouth
thin upper vermilion
thick lower vermilion

Head And Neck Eyes:
visual impairment
long eyelashes
thick eyebrows

Head And Neck Nose:
thick nasal alae
anteverted nostrils
broad nose
flat nasal bridge

Skin Nails Hair Hair:
sparse scalp hair
hypertrichosis

Skeletal:
delayed bone age

Cardiovascular Heart:
congenital heart defects

Abdomen Gastrointestinal:
feeding problems

Skeletal Feet:
hypoplastic to absent terminal phalanges (especially fifth toe)

Skin Nails Hair Nails:
hypoplastic or absent nails

Clinical features from OMIM:

614609

MGI Mouse Phenotypes related to Coffin-Siris Syndrome 4:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.43 SCN2A SCN4A SCN5A SCN8A SCN9A SMARCA4
2 respiratory system MP:0005388 8.92 SCN2A SCN4A SCN8A SMARCA4

Drugs & Therapeutics for Coffin-Siris Syndrome 4

Search Clinical Trials , NIH Clinical Center for Coffin-Siris Syndrome 4

Genetic Tests for Coffin-Siris Syndrome 4

Genetic tests related to Coffin-Siris Syndrome 4:

# Genetic test Affiliating Genes
1 Mental Retardation, Autosomal Dominant 16 30 SMARCA4

Anatomical Context for Coffin-Siris Syndrome 4

MalaCards organs/tissues related to Coffin-Siris Syndrome 4:

42
Bone, Heart

Publications for Coffin-Siris Syndrome 4

Variations for Coffin-Siris Syndrome 4

UniProtKB/Swiss-Prot genetic disease variations for Coffin-Siris Syndrome 4:

76
# Symbol AA change Variation ID SNP ID
1 SMARCA4 p.Thr859Met VAR_068210 rs281875226
2 SMARCA4 p.Arg885Cys VAR_068211 rs281875227
3 SMARCA4 p.Leu921Phe VAR_068212 rs281875228
4 SMARCA4 p.Met1011Thr VAR_068213 rs281875229
5 SMARCA4 p.Arg1157Gly VAR_068214 rs281875230

ClinVar genetic disease variations for Coffin-Siris Syndrome 4:

6 (show all 26)
# Gene Variation Type Significance SNP ID Assembly Location
1 SMARCA4 NM_001128849.1(SMARCA4): c.2936G> A (p.Arg979Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs797045981 GRCh37 Chromosome 19, 11134270: 11134270
2 SMARCA4 NM_001128849.1(SMARCA4): c.2936G> A (p.Arg979Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs797045981 GRCh38 Chromosome 19, 11023594: 11023594
3 SMARCA4 NM_001128849.1(SMARCA4): c.3734C> G (p.Ala1245Gly) single nucleotide variant Likely pathogenic rs797045984 GRCh38 Chromosome 19, 11033477: 11033477
4 SMARCA4 NM_001128849.1(SMARCA4): c.3734C> G (p.Ala1245Gly) single nucleotide variant Likely pathogenic rs797045984 GRCh37 Chromosome 19, 11144153: 11144153
5 SMARCA4 NM_003072.3(SMARCA4): c.1636_1638delAAG (p.Lys546del) deletion Pathogenic rs876657378 GRCh38 Chromosome 19, 10996255: 10996257
6 SMARCA4 NM_003072.3(SMARCA4): c.1636_1638delAAG (p.Lys546del) deletion Pathogenic rs876657378 GRCh37 Chromosome 19, 11106931: 11106933
7 SMARCA4 NM_003072.3(SMARCA4): c.2576C> T (p.Thr859Met) single nucleotide variant Pathogenic rs281875226 GRCh37 Chromosome 19, 11130337: 11130337
8 SMARCA4 NM_003072.3(SMARCA4): c.2576C> T (p.Thr859Met) single nucleotide variant Pathogenic rs281875226 GRCh38 Chromosome 19, 11019661: 11019661
9 SMARCA4 NM_003072.3(SMARCA4): c.2653C> T (p.Arg885Cys) single nucleotide variant Pathogenic rs281875227 GRCh37 Chromosome 19, 11132437: 11132437
10 SMARCA4 NM_003072.3(SMARCA4): c.2653C> T (p.Arg885Cys) single nucleotide variant Pathogenic rs281875227 GRCh38 Chromosome 19, 11021761: 11021761
11 SMARCA4 NM_003072.3(SMARCA4): c.2761C> T (p.Leu921Phe) single nucleotide variant Pathogenic rs281875228 GRCh37 Chromosome 19, 11132545: 11132545
12 SMARCA4 NM_003072.3(SMARCA4): c.2761C> T (p.Leu921Phe) single nucleotide variant Pathogenic rs281875228 GRCh38 Chromosome 19, 11021869: 11021869
13 SMARCA4 NM_003072.3(SMARCA4): c.3032T> C (p.Met1011Thr) single nucleotide variant Pathogenic rs281875229 GRCh37 Chromosome 19, 11135065: 11135065
14 SMARCA4 NM_003072.3(SMARCA4): c.3032T> C (p.Met1011Thr) single nucleotide variant Pathogenic rs281875229 GRCh38 Chromosome 19, 11024389: 11024389
15 SMARCA4 NM_003072.3(SMARCA4): c.3469C> G (p.Arg1157Gly) single nucleotide variant Pathogenic rs281875230 GRCh37 Chromosome 19, 11141492: 11141492
16 SMARCA4 NM_003072.3(SMARCA4): c.3469C> G (p.Arg1157Gly) single nucleotide variant Pathogenic rs281875230 GRCh38 Chromosome 19, 11030816: 11030816
17 SMARCA4 NM_001128849.1(SMARCA4): c.3922C> T (p.Arg1308Trp) single nucleotide variant Likely pathogenic rs587779750 GRCh37 Chromosome 19, 11144847: 11144847
18 SMARCA4 NM_001128849.1(SMARCA4): c.3922C> T (p.Arg1308Trp) single nucleotide variant Likely pathogenic rs587779750 GRCh38 Chromosome 19, 11034171: 11034171
19 SMARCA4 NM_001128849.1(SMARCA4): c.2851G> A (p.Gly951Arg) single nucleotide variant Pathogenic rs1060499936 GRCh37 Chromosome 19, 11132635: 11132635
20 SMARCA4 NM_001128849.1(SMARCA4): c.2851G> A (p.Gly951Arg) single nucleotide variant Pathogenic rs1060499936 GRCh38 Chromosome 19, 11021959: 11021959
21 SMARCA4 NM_001128849.1(SMARCA4): c.3127C> T (p.Arg1043Trp) single nucleotide variant Likely pathogenic rs770014321 GRCh37 Chromosome 19, 11136143: 11136143
22 SMARCA4 NM_001128849.1(SMARCA4): c.3127C> T (p.Arg1043Trp) single nucleotide variant Likely pathogenic rs770014321 GRCh38 Chromosome 19, 11025467: 11025467
23 SMARCA4 NM_001128849.1(SMARCA4): c.3608G> A (p.Arg1203His) single nucleotide variant Conflicting interpretations of pathogenicity rs770680174 GRCh37 Chromosome 19, 11144027: 11144027
24 SMARCA4 NM_001128849.1(SMARCA4): c.3608G> A (p.Arg1203His) single nucleotide variant Conflicting interpretations of pathogenicity rs770680174 GRCh38 Chromosome 19, 11033351: 11033351
25 SMARCA4 NC_000019.9: g.11114016_11114073del deletion Likely pathogenic GRCh38 Chromosome 19, 11003343: 11003400
26 SMARCA4 NC_000019.9: g.11114016_11114073del deletion Likely pathogenic GRCh37 Chromosome 19, 11114016: 11114073

Expression for Coffin-Siris Syndrome 4

Search GEO for disease gene expression data for Coffin-Siris Syndrome 4.

Pathways for Coffin-Siris Syndrome 4

Pathways related to Coffin-Siris Syndrome 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.11 SCN2A SCN4A SCN5A SCN8A SCN9A
2
Show member pathways
13.04 SCN2A SCN4A SCN5A SCN8A SCN9A
3
Show member pathways
12.72 SCN2A SCN4A SCN5A SCN8A SCN9A
4
Show member pathways
12.49 SCN2A SCN4A SCN5A SCN8A SCN9A
5
Show member pathways
12.31 SCN2A SCN4A SCN5A SCN8A SCN9A
6 12.19 SCN2A SCN4A SCN5A SCN8A SCN9A
7
Show member pathways
11.65 SCN2A SCN4A SCN5A SCN8A SCN9A
8
Show member pathways
11.23 SCN2A SCN4A SCN5A SCN8A SCN9A
9 10.5 SCN2A SCN4A SCN5A SCN8A SCN9A

GO Terms for Coffin-Siris Syndrome 4

Cellular components related to Coffin-Siris Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 axon GO:0030424 9.35 SCN2A SCN4A SCN5A SCN8A SCN9A
2 intercalated disc GO:0014704 9.32 SCN2A SCN5A
3 T-tubule GO:0030315 9.26 SCN2A SCN5A
4 node of Ranvier GO:0033268 9.16 SCN2A SCN8A
5 voltage-gated sodium channel complex GO:0001518 9.02 SCN2A SCN4A SCN5A SCN8A SCN9A

Biological processes related to Coffin-Siris Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.8 SCN2A SCN4A SCN5A SCN8A SCN9A
2 transmembrane transport GO:0055085 9.77 SCN2A SCN4A SCN5A SCN8A SCN9A
3 ion transmembrane transport GO:0034220 9.73 SCN2A SCN5A SCN8A SCN9A
4 regulation of ion transmembrane transport GO:0034765 9.72 SCN2A SCN4A SCN5A SCN8A SCN9A
5 nervous system development GO:0007399 9.65 SCN2A SCN8A SMARCA4
6 sodium ion transport GO:0006814 9.65 SCN2A SCN4A SCN5A SCN8A SCN9A
7 sodium ion transmembrane transport GO:0035725 9.55 SCN2A SCN4A SCN5A SCN8A SCN9A
8 myelination GO:0042552 9.46 SCN2A SCN8A
9 neuronal action potential GO:0019228 9.35 SCN2A SCN4A SCN5A SCN8A SCN9A
10 membrane depolarization during action potential GO:0086010 9.02 SCN2A SCN4A SCN5A SCN8A SCN9A

Molecular functions related to Coffin-Siris Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion channel activity GO:0005216 9.65 SCN2A SCN4A SCN5A SCN8A SCN9A
2 voltage-gated ion channel activity GO:0005244 9.55 SCN2A SCN4A SCN5A SCN8A SCN9A
3 sodium channel activity GO:0005272 9.35 SCN2A SCN4A SCN5A SCN8A SCN9A
4 voltage-gated sodium channel activity GO:0005248 9.02 SCN2A SCN4A SCN5A SCN8A SCN9A

Sources for Coffin-Siris Syndrome 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
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45 MeSH
46 MESH via Orphanet
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50 NCI
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59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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