CSS4
MCID: CFF009
MIFTS: 42

Coffin-Siris Syndrome 4 (CSS4)

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

Aliases & Classifications for Coffin-Siris Syndrome 4

MalaCards integrated aliases for Coffin-Siris Syndrome 4:

Name: Coffin-Siris Syndrome 4 57 12 74 15
Mental Retardation, Autosomal Dominant 16 57 74 29 13 6 72
Mrd16 57 12 74
Css4 57 12 74
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:



External Ids:

Disease Ontology 12 DOID:0070046
UMLS 72 C3553249

Summaries for Coffin-Siris Syndrome 4

UniProtKB/Swiss-Prot : 74 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 heart, bone and skeletal muscle, 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 : 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

Human phenotypes related to Coffin-Siris Syndrome 4:

32 (show all 29)
# Description HPO Frequency HPO Source Accession
1 seizures 32 very rare (1%) HP:0001250
2 microcephaly 32 very rare (1%) HP:0000252
3 visual impairment 32 very rare (1%) HP:0000505
4 thick eyebrow 32 very rare (1%) HP:0000574
5 dandy-walker malformation 32 very rare (1%) HP:0001305
6 sparse scalp hair 32 very rare (1%) HP:0002209
7 long eyelashes 32 very rare (1%) HP:0000527
8 hirsutism 32 very rare (1%) HP:0001007
9 intellectual disability 32 HP:0001249
10 scoliosis 32 HP:0002650
11 macroglossia 32 HP:0000158
12 coarse facial features 32 HP:0000280
13 hearing impairment 32 HP:0000365
14 global developmental delay 32 HP:0001263
15 delayed skeletal maturation 32 HP:0002750
16 depressed nasal bridge 32 HP:0005280
17 anteverted nares 32 HP:0000463
18 short stature 32 HP:0004322
19 generalized hypotonia 32 HP:0001290
20 feeding difficulties 32 HP:0011968
21 thick nasal alae 32 HP:0009928
22 intrauterine growth retardation 32 HP:0001511
23 wide mouth 32 HP:0000154
24 wide nose 32 HP:0000445
25 abnormality of cardiovascular system morphology 32 HP:0030680
26 hypertrichosis 32 HP:0000998
27 abnormal heart morphology 32 HP:0001627
28 abnormal corpus callosum morphology 32 HP:0001273
29 aplasia/hypoplasia of the distal phalanges of the hand 32 HP:0009835

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

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
Heart, Bone, Skeletal Muscle

Publications for Coffin-Siris Syndrome 4

Articles related to Coffin-Siris Syndrome 4:

# Title Authors PMID Year
1
Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. 8 71
22426308 2012
2
Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A. 8
25168959 2014
3
Mapping of scorpion toxin receptor sites at voltage-gated sodium channels. 38
22694883 2012
4
Conserved functional surface of antimammalian scorpion β-toxins. 38
22471309 2012
5
Partial agonist and antagonist activities of a mutant scorpion beta-toxin on sodium channels. 38
20682774 2010
6
Miniaturization of scorpion beta-toxins uncovers a putative ancestral surface of interaction with voltage-gated sodium channels. 38
18339620 2008
7
Design of a specific activator for skeletal muscle sodium channels uncovers channel architecture. 38
17686768 2007
8
Subtype specificity of scorpion beta-toxin Tz1 interaction with voltage-gated sodium channels is determined by the pore loop of domain 3. 38
16638971 2006
9
Common features in the functional surface of scorpion beta-toxins and elements that confer specificity for insect and mammalian voltage-gated sodium channels. 38
15569679 2005

Variations for Coffin-Siris Syndrome 4

ClinVar genetic disease variations for Coffin-Siris Syndrome 4:

6 (show all 35)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 SMARCA4 NM_001128849.2(SMARCA4): c.2851G> A (p.Gly951Arg) single nucleotide variant Pathogenic rs1060499936 19:11132635-11132635 19:11021959-11021959
2 SMARCA4 NM_001128849.2(SMARCA4): c.1633_1635AAG[1] (p.Lys546del) short repeat Pathogenic rs876657378 19:11106931-11106933 19:10996255-10996257
3 SMARCA4 NM_001128849.2(SMARCA4): c.2576C> T (p.Thr859Met) single nucleotide variant Pathogenic rs281875226 19:11130337-11130337 19:11019661-11019661
4 SMARCA4 NM_001128849.2(SMARCA4): c.2653C> T (p.Arg885Cys) single nucleotide variant Pathogenic rs281875227 19:11132437-11132437 19:11021761-11021761
5 SMARCA4 NM_001128849.2(SMARCA4): c.2761C> T (p.Leu921Phe) single nucleotide variant Pathogenic rs281875228 19:11132545-11132545 19:11021869-11021869
6 SMARCA4 NM_001128849.2(SMARCA4): c.3032T> C (p.Met1011Thr) single nucleotide variant Pathogenic rs281875229 19:11135065-11135065 19:11024389-11024389
7 SMARCA4 NM_001128849.2(SMARCA4): c.3469C> G (p.Arg1157Gly) single nucleotide variant Pathogenic rs281875230 19:11141492-11141492 19:11030816-11030816
8 SMARCA4 NM_001128849.2(SMARCA4): c.3922C> T (p.Arg1308Trp) single nucleotide variant Likely pathogenic rs587779750 19:11144847-11144847 19:11034171-11034171
9 SMARCA4 NM_001128849.2(SMARCA4): c.3127C> T (p.Arg1043Trp) single nucleotide variant Likely pathogenic rs770014321 19:11136143-11136143 19:11025467-11025467
10 SMARCA4 NM_001128849.2(SMARCA4): c.1947_2001+3del deletion Likely pathogenic 19:11114016-11114073 19:11003343-11003400
11 SMARCA4 NM_001128849.2(SMARCA4): c.2647G> A (p.Gly883Ser) single nucleotide variant Likely pathogenic 19:11132431-11132431 19:11021755-11021755
12 SMARCA4 NM_001128849.2(SMARCA4): c.3734C> G (p.Ala1245Gly) single nucleotide variant Likely pathogenic rs797045984 19:11144153-11144153 19:11033477-11033477
13 SMARCA4 NM_001128849.2(SMARCA4): c.3608G> A (p.Arg1203His) single nucleotide variant Conflicting interpretations of pathogenicity rs770680174 19:11144027-11144027 19:11033351-11033351
14 SMARCA4 NM_001128849.2(SMARCA4): c.2936G> A (p.Arg979Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs797045981 19:11134270-11134270 19:11023594-11023594
15 SMARCA4 NM_001128849.2(SMARCA4): c.407C> T (p.Ala136Val) single nucleotide variant Uncertain significance rs535299273 19:11096916-11096916 19:10986240-10986240
16 SMARCA4 NM_001128849.2(SMARCA4): c.709G> A (p.Gly237Ser) single nucleotide variant Uncertain significance rs1555753727 19:11097218-11097218 19:10986542-10986542
17 SMARCA4 NM_001128849.2(SMARCA4): c.914C> T (p.Pro305Leu) single nucleotide variant Uncertain significance rs138097741 19:11098396-11098396 19:10987720-10987720
18 SMARCA4 NM_001128849.2(SMARCA4): c.4922T> C (p.Leu1641Pro) single nucleotide variant Uncertain significance rs755493468 19:11170778-11170778 19:11060102-11060102
19 SMARCA4 NM_001128849.2(SMARCA4): c.4472C> T (p.Thr1491Ile) single nucleotide variant Uncertain significance rs1555788341 19:11152188-11152188 19:11041512-11041512
20 SMARCA4 NM_001128849.2(SMARCA4): c.422C> T (p.Ser141Leu) single nucleotide variant Uncertain significance rs1060502073 19:11096931-11096931 19:10986255-10986255
21 SMARCA4 NM_001128849.2(SMARCA4): c.4967C> T (p.Pro1656Leu) single nucleotide variant Uncertain significance rs756255060 19:11170823-11170823 19:11060147-11060147
22 SMARCA4 NM_001128849.2(SMARCA4): c.4972G> A (p.Val1658Met) single nucleotide variant Uncertain significance rs757412819 19:11170828-11170828 19:11060152-11060152
23 SMARCA4 NM_001128849.2(SMARCA4): c.1889G> A (p.Gly630Asp) single nucleotide variant Uncertain significance rs749533909 19:11113781-11113781 19:11003105-11003105
24 SMARCA4 NM_001128849.2(SMARCA4): c.3830C> T (p.Pro1277Leu) single nucleotide variant Uncertain significance rs746219091 19:11144498-11144498 19:11033822-11033822
25 SMARCA4 NM_001128849.2(SMARCA4): c.1018G> A (p.Ala340Thr) single nucleotide variant Uncertain significance rs371214327 19:11098500-11098500 19:10987824-10987824
26 SMARCA4 NM_001128849.2(SMARCA4): c.3436G> A (p.Gly1146Ser) single nucleotide variant Uncertain significance rs200007170 19:11141459-11141459 19:11030783-11030783
27 SMARCA4 NM_001128849.2(SMARCA4): c.4351G> A (p.Ala1451Thr) single nucleotide variant Uncertain significance rs374722116 19:11152067-11152067 19:11041391-11041391
28 SMARCA4 NM_001128849.2(SMARCA4): c.4913A> G (p.Gln1638Arg) single nucleotide variant Uncertain significance rs878854231 19:11170769-11170769 19:11060093-11060093
29 SMARCA4 NM_001128849.2(SMARCA4): c.2438+4A> C single nucleotide variant Uncertain significance 19:11123792-11123792 19:11013116-11013116
30 SMARCA4 NM_001128849.2(SMARCA4): c.4520+6C> T single nucleotide variant Uncertain significance rs778283753 19:11152242-11152242 19:11041566-11041566
31 SMARCA4 NM_001128849.2(SMARCA4): c.778A> C (p.Met260Leu) single nucleotide variant Uncertain significance rs1064795842 19:11097598-11097598 19:10986922-10986922
32 SMARCA4 NM_001128849.2(SMARCA4): c.952G> A (p.Val318Ile) single nucleotide variant Uncertain significance rs758091260 19:11098434-11098434 19:10987758-10987758
33 SMARCA4 NM_001128849.2(SMARCA4): c.1108C> T (p.Arg370Cys) single nucleotide variant Uncertain significance rs1436490540 19:11098590-11098590 19:10987914-10987914
34 SMARCA4 NM_001128849.2(SMARCA4): c.1098C> G (p.Ile366Met) single nucleotide variant Uncertain significance rs532242119 19:11098580-11098580 19:10987904-10987904
35 SMARCA4 NM_001128849.2(SMARCA4): c.829C> T (p.Pro277Ser) single nucleotide variant Uncertain significance rs767947665 19:11097649-11097649 19:10986973-10986973

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

74
# 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

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 SCN9A SCN8A SCN5A SCN4A SCN2A
2
Show member pathways
13.04 SCN9A SCN8A SCN5A SCN4A SCN2A
3
Show member pathways
12.67 SCN9A SCN8A SCN5A SCN4A SCN2A
4
Show member pathways
12.49 SCN9A SCN8A SCN5A SCN4A SCN2A
5
Show member pathways
12.31 SCN9A SCN8A SCN5A SCN4A SCN2A
6 12.19 SCN9A SCN8A SCN5A SCN4A SCN2A
7
Show member pathways
11.65 SCN9A SCN8A SCN5A SCN4A SCN2A
8
Show member pathways
11.23 SCN9A SCN8A SCN5A SCN4A SCN2A
9 10.5 SCN9A SCN8A SCN5A SCN4A SCN2A

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 SCN9A SCN8A SCN5A SCN4A SCN2A
2 intercalated disc GO:0014704 9.32 SCN5A SCN2A
3 T-tubule GO:0030315 9.26 SCN5A SCN2A
4 node of Ranvier GO:0033268 9.16 SCN8A SCN2A
5 voltage-gated sodium channel complex GO:0001518 9.02 SCN9A SCN8A SCN5A SCN4A SCN2A

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

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 SCN9A SCN8A SCN5A SCN4A SCN2A
2 voltage-gated ion channel activity GO:0005244 9.55 SCN9A SCN8A SCN5A SCN4A SCN2A
3 sodium channel activity GO:0005272 9.35 SCN9A SCN8A SCN5A SCN4A SCN2A
4 voltage-gated sodium channel activity GO:0005248 9.02 SCN9A SCN8A SCN5A SCN4A SCN2A

Sources for Coffin-Siris Syndrome 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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
46 MGI
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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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