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 57 12 75 15
Mental Retardation, Autosomal Dominant 16 57 75 29 13 6 73
Mrd16 57 12 75
Css4 57 12 75
Mental Retardation, Autosomal Dominant 16; Mrd16 57
Autosomal Dominant Mental Retardation 16 12
Coffin-Siris Syndrome, Type 4 ) 40

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
coffin-siris syndrome 4:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Coffin-Siris Syndrome 4

UniProtKB/Swiss-Prot : 75 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 intellectual disability and seizures

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

OMIM : 57 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

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Coffin-Siris Syndrome 4:

32 (show all 28)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 32 HP:0001249
2 seizures 32 very rare (1%) HP:0001250
3 scoliosis 32 HP:0002650
4 macroglossia 32 HP:0000158
5 coarse facial features 32 HP:0000280
6 hearing impairment 32 HP:0000365
7 global developmental delay 32 HP:0001263
8 delayed skeletal maturation 32 HP:0002750
9 depressed nasal bridge 32 HP:0005280
10 microcephaly 32 very rare (1%) HP:0000252
11 anteverted nares 32 HP:0000463
12 visual impairment 32 very rare (1%) HP:0000505
13 thick eyebrow 32 very rare (1%) HP:0000574
14 short stature 32 HP:0004322
15 feeding difficulties 32 HP:0011968
16 thick nasal alae 32 HP:0009928
17 intrauterine growth retardation 32 HP:0001511
18 wide mouth 32 HP:0000154
19 sparse scalp hair 32 very rare (1%) HP:0002209
20 long eyelashes 32 very rare (1%) HP:0000527
21 wide nose 32 HP:0000445
22 dandy-walker malformation 32 very rare (1%) HP:0001305
23 generalized hypotonia 32 HP:0001290
24 abnormality of cardiovascular system morphology 32 HP:0030680
25 hirsutism 32 very rare (1%) HP:0001007
26 hypertrichosis 32 HP:0000998
27 aplasia/hypoplasia of the distal phalanges of the hand 32 HP:0009835
28 abnormal corpus callosum morphology 32 HP:0001273

MGI Mouse Phenotypes related to Coffin-Siris Syndrome 4:

46
# 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 29 SMARCA4

Anatomical Context for Coffin-Siris Syndrome 4

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

41
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:

75
# 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 22)
# Gene Variation Type Significance SNP ID Assembly Location
1 SMARCA4 NM_001128849.1(SMARCA4): c.1636_1638delAAG (p.Lys546del) deletion Pathogenic rs876657378 GRCh38 Chromosome 19, 10996255: 10996257
2 SMARCA4 NM_001128849.1(SMARCA4): c.1636_1638delAAG (p.Lys546del) deletion Pathogenic rs876657378 GRCh37 Chromosome 19, 11106931: 11106933
3 SMARCA4 NM_003072.3(SMARCA4): c.2576C> T (p.Thr859Met) single nucleotide variant Pathogenic rs281875226 GRCh37 Chromosome 19, 11130337: 11130337
4 SMARCA4 NM_003072.3(SMARCA4): c.2576C> T (p.Thr859Met) single nucleotide variant Pathogenic rs281875226 GRCh38 Chromosome 19, 11019661: 11019661
5 SMARCA4 NM_003072.3(SMARCA4): c.2653C> T (p.Arg885Cys) single nucleotide variant Pathogenic rs281875227 GRCh37 Chromosome 19, 11132437: 11132437
6 SMARCA4 NM_003072.3(SMARCA4): c.2653C> T (p.Arg885Cys) single nucleotide variant Pathogenic rs281875227 GRCh38 Chromosome 19, 11021761: 11021761
7 SMARCA4 NM_003072.3(SMARCA4): c.2761C> T (p.Leu921Phe) single nucleotide variant Pathogenic rs281875228 GRCh37 Chromosome 19, 11132545: 11132545
8 SMARCA4 NM_003072.3(SMARCA4): c.2761C> T (p.Leu921Phe) single nucleotide variant Pathogenic rs281875228 GRCh38 Chromosome 19, 11021869: 11021869
9 SMARCA4 NM_003072.3(SMARCA4): c.3032T> C (p.Met1011Thr) single nucleotide variant Pathogenic rs281875229 GRCh37 Chromosome 19, 11135065: 11135065
10 SMARCA4 NM_003072.3(SMARCA4): c.3032T> C (p.Met1011Thr) single nucleotide variant Pathogenic rs281875229 GRCh38 Chromosome 19, 11024389: 11024389
11 SMARCA4 NM_003072.3(SMARCA4): c.3469C> G (p.Arg1157Gly) single nucleotide variant Pathogenic rs281875230 GRCh37 Chromosome 19, 11141492: 11141492
12 SMARCA4 NM_003072.3(SMARCA4): c.3469C> G (p.Arg1157Gly) single nucleotide variant Pathogenic rs281875230 GRCh38 Chromosome 19, 11030816: 11030816
13 SMARCA4 NM_001128849.1(SMARCA4): c.3922C> T (p.Arg1308Trp) single nucleotide variant Likely pathogenic rs587779750 GRCh37 Chromosome 19, 11144847: 11144847
14 SMARCA4 NM_001128849.1(SMARCA4): c.3922C> T (p.Arg1308Trp) single nucleotide variant Likely pathogenic rs587779750 GRCh38 Chromosome 19, 11034171: 11034171
15 SMARCA4 NM_001128849.1(SMARCA4): c.3734C> G (p.Ala1245Gly) single nucleotide variant Likely pathogenic rs797045984 GRCh38 Chromosome 19, 11033477: 11033477
16 SMARCA4 NM_001128849.1(SMARCA4): c.3734C> G (p.Ala1245Gly) single nucleotide variant Likely pathogenic rs797045984 GRCh37 Chromosome 19, 11144153: 11144153
17 SMARCA4 NM_001128849.1(SMARCA4): c.2851G> A (p.Gly951Arg) single nucleotide variant Pathogenic rs1060499936 GRCh37 Chromosome 19, 11132635: 11132635
18 SMARCA4 NM_001128849.1(SMARCA4): c.2851G> A (p.Gly951Arg) single nucleotide variant Pathogenic rs1060499936 GRCh38 Chromosome 19, 11021959: 11021959
19 SMARCA4 NM_001128849.1(SMARCA4): c.3127C> T (p.Arg1043Trp) single nucleotide variant Likely pathogenic rs770014321 GRCh37 Chromosome 19, 11136143: 11136143
20 SMARCA4 NM_001128849.1(SMARCA4): c.3127C> T (p.Arg1043Trp) single nucleotide variant Likely pathogenic rs770014321 GRCh38 Chromosome 19, 11025467: 11025467
21 SMARCA4 NM_001128849.1(SMARCA4): c.3608G> A (p.Arg1203His) single nucleotide variant Conflicting interpretations of pathogenicity rs770680174 GRCh37 Chromosome 19, 11144027: 11144027
22 SMARCA4 NM_001128849.1(SMARCA4): c.3608G> A (p.Arg1203His) single nucleotide variant Conflicting interpretations of pathogenicity rs770680174 GRCh38 Chromosome 19, 11033351: 11033351

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
12.67 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 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
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49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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