CSS4
MCID: CFF009
MIFTS: 43

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 56 12 73 15
Mental Retardation, Autosomal Dominant 16 56 73 29 13 6 71
Mrd16 56 12 73
Css4 56 12 73
Mental Retardation, Autosomal Dominant 16; Mrd16 56
Autosomal Dominant Mental Retardation 16 12
Coffin-Siris Syndrome, Type 4 39

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant


HPO:

31
coffin-siris syndrome 4:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Coffin-Siris Syndrome 4

UniProtKB/Swiss-Prot : 73 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 endometrioid ovary carcinoma and alpha thalassemia-x-linked intellectual disability syndrome. 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 Chromatin organization and L1CAM interactions. Affiliated tissues include bone, heart 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 : 56 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

Diseases in the Coffin-Siris Syndrome 1 family:

Coffin-Siris Syndrome 2 Coffin-Siris Syndrome 3
Coffin-Siris Syndrome 4 Coffin-Siris Syndrome 9
Coffin-Siris Syndrome 5 Coffin-Siris Syndrome 6
Coffin-Siris Syndrome 7 Coffin-Siris Syndrome 8
Coffin-Siris Syndrome 10

Diseases related to Coffin-Siris Syndrome 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 32)
# Related Disease Score Top Affiliating Genes
1 endometrioid ovary carcinoma 10.3 SMARCA4 H2AC18
2 alpha thalassemia-x-linked intellectual disability syndrome 10.3 SMARCA4 H2AC18
3 neurilemmomatosis 10.1 SMARCE1 SMARCA4 ARID2
4 hypertrichosis 10.1 SMARCE1 SMARCA4 ARID2
5 landau-kleffner syndrome 10.0 SCN8A SCN2A
6 low-grade astrocytoma 10.0 SCN8A SCN2A
7 infancy electroclinical syndrome 9.9 SCN8A SCN2A
8 alpha-thalassemia 9.9 SMARCA4 SCN2A H2AC18
9 electroclinical syndrome 9.9 SCN8A SCN2A
10 blood protein disease 9.9 SCN2A H2AC18
11 non-syndromic intellectual disability 9.9 SMARCE1 SMARCA4 H2AC18 ARID2
12 childhood electroclinical syndrome 9.9 SCN8A SCN2A
13 rhabdoid cancer 9.9 SMARCE1 SMARCA4 H2AC18 ARID2
14 neonatal period electroclinical syndrome 9.8 SCN8A SCN2A
15 coffin-siris syndrome 3 9.8 SMARCE1 H2AC18 CMAS ARID2
16 familial periodic paralysis 9.7 SCN4A SCN2A
17 erythromelalgia 9.7 SCN8A SCN4A
18 hyperkalemic periodic paralysis 9.7 SCN4A SCN2A
19 paine syndrome 9.6 SCN8A SCN4A H2AC18
20 somatoform disorder 9.6 SCN8A SCN4A H2AC18
21 coffin-siris syndrome 2 9.6 SMARCE1 H2AC18 CNDP2 CMAS ARID2
22 neuromuscular junction disease 9.4 SCN4A H2AC18
23 hypokalemic periodic paralysis, type 1 9.4 SCN4A SCN2A
24 episodic ataxia 9.4 SCN8A SCN4A SCN2A
25 epileptic encephalopathy, early infantile, 6 9.4 SCN8A SCN4A SCN2A
26 generalized epilepsy with febrile seizures plus 9.4 SCN8A SCN4A SCN2A
27 epilepsy, idiopathic generalized 9.4 SCN8A SCN4A SCN2A
28 early infantile epileptic encephalopathy 9.3 SCN8A SCN4A SCN2A
29 brugada syndrome 9.2 SCN8A SCN4A SCN2A
30 migraine with or without aura 1 9.2 SCN8A SCN4A SCN2A H2AC18
31 autosomal dominant non-syndromic intellectual disability 8.3 SMARCE1 SMARCA4 SCN8A SCN2A MID1IP1 H2AC18
32 coffin-siris syndrome 1 8.1 SMARCE1 SMARCA4 SLC44A3 SCN2A PALM H2AC18

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:

31 (show all 29)
# Description HPO Frequency HPO Source Accession
1 seizures 31 very rare (1%) HP:0001250
2 microcephaly 31 very rare (1%) HP:0000252
3 visual impairment 31 very rare (1%) HP:0000505
4 thick eyebrow 31 very rare (1%) HP:0000574
5 dandy-walker malformation 31 very rare (1%) HP:0001305
6 sparse scalp hair 31 very rare (1%) HP:0002209
7 long eyelashes 31 very rare (1%) HP:0000527
8 hirsutism 31 very rare (1%) HP:0001007
9 intellectual disability 31 HP:0001249
10 scoliosis 31 HP:0002650
11 macroglossia 31 HP:0000158
12 coarse facial features 31 HP:0000280
13 hearing impairment 31 HP:0000365
14 global developmental delay 31 HP:0001263
15 delayed skeletal maturation 31 HP:0002750
16 depressed nasal bridge 31 HP:0005280
17 short stature 31 HP:0004322
18 feeding difficulties 31 HP:0011968
19 intrauterine growth retardation 31 HP:0001511
20 anteverted nares 31 HP:0000463
21 generalized hypotonia 31 HP:0001290
22 thick nasal alae 31 HP:0009928
23 wide mouth 31 HP:0000154
24 abnormal heart morphology 31 HP:0001627
25 wide nose 31 HP:0000445
26 abnormality of cardiovascular system morphology 31 HP:0030680
27 hypertrichosis 31 HP:0000998
28 abnormal corpus callosum morphology 31 HP:0001273
29 aplasia/hypoplasia of the distal phalanges of the hand 31 HP:0009835

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
scoliosis

Head And Neck Ears:
hearing impairment

Growth Other:
intrauterine growth retardation
poor overall growth

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

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

Growth Height:
short stature

Head And Neck Eyes:
visual impairment
long eyelashes
thick eyebrows

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

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:

40
Bone, Heart, Skeletal Muscle, Eye, Ovary

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. 56 6
22426308 2012
2
Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A. 56
25168959 2014
3
Mapping of scorpion toxin receptor sites at voltage-gated sodium channels. 61
22694883 2012
4
Conserved functional surface of antimammalian scorpion β-toxins. 61
22471309 2012
5
Partial agonist and antagonist activities of a mutant scorpion beta-toxin on sodium channels. 61
20682774 2010
6
Miniaturization of scorpion beta-toxins uncovers a putative ancestral surface of interaction with voltage-gated sodium channels. 61
18339620 2008
7
Design of a specific activator for skeletal muscle sodium channels uncovers channel architecture. 61
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. 61
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. 61
15569679 2005

Variations for Coffin-Siris Syndrome 4

ClinVar genetic disease variations for Coffin-Siris Syndrome 4:

6 (show all 38) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SMARCA4 NM_003072.4(SMARCA4):c.1633_1635AAG[1] (p.Lys546del)short repeat Pathogenic 30342 rs876657378 19:11106926-11106928 19:10996250-10996252
2 SMARCA4 NM_003072.4(SMARCA4):c.2576C>T (p.Thr859Met)SNV Pathogenic 30343 rs281875226 19:11130337-11130337 19:11019661-11019661
3 SMARCA4 NM_003072.4(SMARCA4):c.2653C>T (p.Arg885Cys)SNV Pathogenic 30344 rs281875227 19:11132437-11132437 19:11021761-11021761
4 SMARCA4 NM_003072.4(SMARCA4):c.2761C>T (p.Leu921Phe)SNV Pathogenic 30345 rs281875228 19:11132545-11132545 19:11021869-11021869
5 SMARCA4 NM_003072.4(SMARCA4):c.3032T>C (p.Met1011Thr)SNV Pathogenic 30346 rs281875229 19:11135065-11135065 19:11024389-11024389
6 SMARCA4 NM_003072.4(SMARCA4):c.3469C>G (p.Arg1157Gly)SNV Pathogenic 30347 rs281875230 19:11141492-11141492 19:11030816-11030816
7 SMARCA4 NM_003072.4(SMARCA4):c.2851G>A (p.Gly951Arg)SNV Pathogenic 403671 rs1060499936 19:11132635-11132635 19:11021959-11021959
8 SMARCA4 NM_001128849.3(SMARCA4):c.1675G>A (p.Glu559Lys)SNV Pathogenic 807689 19:11106970-11106970 19:10996294-10996294
9 SMARCA4 NM_003072.4(SMARCA4):c.2704G>A (p.Val902Met)SNV Likely pathogenic 689790 19:11132488-11132488 19:11021812-11021812
10 SMARCA4 NM_001128849.2(SMARCA4):c.3734C>G (p.Ala1245Gly)SNV Likely pathogenic 212251 rs797045984 19:11144153-11144153 19:11033477-11033477
11 SMARCA4 NM_001128849.3(SMARCA4):c.1947_2001+3deldeletion Likely pathogenic 620036 rs1568456200 19:11114014-11114071 19:11003338-11003395
12 SMARCA4 NM_001128849.2(SMARCA4):c.2647G>A (p.Gly883Ser)SNV Likely pathogenic 625157 rs1568486679 19:11132431-11132431 19:11021755-11021755
13 SMARCA4 NM_003072.4(SMARCA4):c.3922C>T (p.Arg1308Trp)SNV Likely pathogenic 126361 rs587779750 19:11144847-11144847 19:11034171-11034171
14 SMARCA4 NM_001128849.2(SMARCA4):c.3127C>T (p.Arg1043Trp)SNV Likely pathogenic 436813 rs770014321 19:11136143-11136143 19:11025467-11025467
15 SMARCA4 NM_001128849.2(SMARCA4):c.3608G>A (p.Arg1203His)SNV Conflicting interpretations of pathogenicity 449452 rs770680174 19:11144027-11144027 19:11033351-11033351
16 SMARCA4 NM_001128849.2(SMARCA4):c.3557C>T (p.Ala1186Val)SNV Conflicting interpretations of pathogenicity 657828 19:11143976-11143976 19:11033300-11033300
17 SMARCA4 NM_001128849.2(SMARCA4):c.2936G>A (p.Arg979Gln)SNV Conflicting interpretations of pathogenicity 212246 rs797045981 19:11134270-11134270 19:11023594-11023594
18 SMARCA4 NM_001128849.2(SMARCA4):c.3830C>T (p.Pro1277Leu)SNV Uncertain significance 212253 rs746219091 19:11144498-11144498 19:11033822-11033822
19 SMARCA4 NM_001128849.2(SMARCA4):c.422C>T (p.Ser141Leu)SNV Uncertain significance 408627 rs1060502073 19:11096931-11096931 19:10986255-10986255
20 SMARCA4 NM_001128849.2(SMARCA4):c.952G>A (p.Val318Ile)SNV Uncertain significance 408669 rs758091260 19:11098434-11098434 19:10987758-10987758
21 SMARCA4 NM_001128849.2(SMARCA4):c.4967C>T (p.Pro1656Leu)SNV Uncertain significance 408631 rs756255060 19:11170823-11170823 19:11060147-11060147
22 SMARCA4 NM_001128849.2(SMARCA4):c.4972G>A (p.Val1658Met)SNV Uncertain significance 408703 rs757412819 19:11170828-11170828 19:11060152-11060152
23 SMARCA4 NM_001128849.2(SMARCA4):c.1889G>A (p.Gly630Asp)SNV Uncertain significance 408664 rs749533909 19:11113781-11113781 19:11003105-11003105
24 SMARCA4 NM_001128849.2(SMARCA4):c.778A>C (p.Met260Leu)SNV Uncertain significance 422533 rs1064795842 19:11097598-11097598 19:10986922-10986922
25 SMARCA4 NM_001128849.2(SMARCA4):c.4520+6C>TSNV Uncertain significance 470402 rs778283753 19:11152242-11152242 19:11041566-11041566
26 SMARCA4 NM_001128849.2(SMARCA4):c.407C>T (p.Ala136Val)SNV Uncertain significance 470381 rs535299273 19:11096916-11096916 19:10986240-10986240
27 SMARCA4 NM_001128849.2(SMARCA4):c.709G>A (p.Gly237Ser)SNV Uncertain significance 470453 rs1555753727 19:11097218-11097218 19:10986542-10986542
28 SMARCA4 NM_001128849.2(SMARCA4):c.914C>T (p.Pro305Leu)SNV Uncertain significance 470468 rs138097741 19:11098396-11098396 19:10987720-10987720
29 SMARCA4 NM_001128849.2(SMARCA4):c.4922T>C (p.Leu1641Pro)SNV Uncertain significance 470424 rs755493468 19:11170778-11170778 19:11060102-11060102
30 SMARCA4 NM_001128849.2(SMARCA4):c.829C>T (p.Pro277Ser)SNV Uncertain significance 480580 rs767947665 19:11097649-11097649 19:10986973-10986973
31 SMARCA4 NM_001128849.2(SMARCA4):c.1098C>G (p.Ile366Met)SNV Uncertain significance 484848 rs532242119 19:11098580-11098580 19:10987904-10987904
32 SMARCA4 NM_001128849.2(SMARCA4):c.1108C>T (p.Arg370Cys)SNV Uncertain significance 480659 rs1436490540 19:11098590-11098590 19:10987914-10987914
33 SMARCA4 NM_001128849.2(SMARCA4):c.4472C>T (p.Thr1491Ile)SNV Uncertain significance 537775 rs1555788341 19:11152188-11152188 19:11041512-11041512
34 SMARCA4 NM_001128849.2(SMARCA4):c.2438+4A>CSNV Uncertain significance 572876 rs771818596 19:11123792-11123792 19:11013116-11013116
35 SMARCA4 NM_001128849.2(SMARCA4):c.1018G>A (p.Ala340Thr)SNV Uncertain significance 238356 rs371214327 19:11098500-11098500 19:10987824-10987824
36 SMARCA4 NM_001128849.2(SMARCA4):c.3436G>A (p.Gly1146Ser)SNV Uncertain significance 238428 rs200007170 19:11141459-11141459 19:11030783-11030783
37 SMARCA4 NM_001128849.2(SMARCA4):c.4351G>A (p.Ala1451Thr)SNV Uncertain significance 238467 rs374722116 19:11152067-11152067 19:11041391-11041391
38 SMARCA4 NM_001128849.2(SMARCA4):c.4913A>G (p.Gln1638Arg)SNV Uncertain significance 238491 rs878854231 19:11170769-11170769 19:11060093-11060093

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

73
# 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
12.4 SMARCE1 SMARCA4 H2AC18 ARID2
2
Show member pathways
11.43 SCN8A SCN4A SCN2A
3
Show member pathways
11.01 SCN8A SCN4A SCN2A
4 10.28 SCN8A 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 9.62 SCN8A SCN4A SCN2A PALM
2 SWI/SNF complex GO:0016514 9.37 SMARCE1 SMARCA4
3 nBAF complex GO:0071565 9.26 SMARCE1 SMARCA4
4 node of Ranvier GO:0033268 9.16 SCN8A SCN2A
5 npBAF complex GO:0071564 8.96 SMARCE1 SMARCA4
6 voltage-gated sodium channel complex GO:0001518 8.8 SCN8A SCN4A SCN2A

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

# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.78 SLC44A3 SCN8A SCN4A SCN2A
2 nervous system development GO:0007399 9.73 SMARCE1 SMARCA4 SCN8A SCN2A
3 chromatin organization GO:0006325 9.62 SMARCE1 SMARCA4 H2AC18 ARID2
4 regulation of ion transmembrane transport GO:0034765 9.58 SCN8A SCN4A SCN2A
5 sodium ion transport GO:0006814 9.54 SCN8A SCN4A SCN2A
6 ATP-dependent chromatin remodeling GO:0043044 9.46 SMARCE1 SMARCA4
7 sodium ion transmembrane transport GO:0035725 9.43 SCN8A SCN4A SCN2A
8 neuronal action potential GO:0019228 9.33 SCN8A SCN4A SCN2A
9 nucleosome disassembly GO:0006337 9.13 SMARCE1 SMARCA4 ARID2
10 membrane depolarization during action potential GO:0086010 8.8 SCN8A 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 9.43 SCN8A SCN4A SCN2A
2 voltage-gated ion channel activity GO:0005244 9.33 SCN8A SCN4A SCN2A
3 nucleosomal DNA binding GO:0031492 9.32 SMARCE1 SMARCA4
4 sodium channel activity GO:0005272 9.13 SCN8A SCN4A SCN2A
5 voltage-gated sodium channel activity GO:0005248 8.8 SCN8A 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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....