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 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 floating-harbor syndrome and spinal canal and spinal cord meningioma. 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 Interaction between L1 and Ankyrins. Affiliated tissues include heart, bone and skeletal muscle, and related phenotypes are microcephaly and visual impairment

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 Coffin-Siris Syndrome 11

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

(show all 29)
# Related Disease Score Top Affiliating Genes
1 floating-harbor syndrome 10.3 SMARCA4 H2AC18
2 spinal canal and spinal cord meningioma 10.3 SMARCE1 SMARCA4
3 spinal meningioma 10.3 SMARCE1 SMARCA4
4 alpha thalassemia-x-linked intellectual disability syndrome 10.3 SMARCA4 H2AC18
5 epilepsy, familial temporal lobe, 1 10.2 SMARCA4 H2AC18
6 paine syndrome 10.1 SCN8A H2AC18
7 epileptic encephalopathy, early infantile, 13 10.1 SCN8A SCN2A
8 low-grade astrocytoma 10.1 SCN8A SCN2A
9 benign familial neonatal epilepsy 10.1 SCN8A SCN2A
10 neurilemmomatosis 10.0 SMARCE1 SMARCA4 ARID2
11 hypertrichosis 10.0 SMARCE1 SMARCA4 ARID2
12 infancy electroclinical syndrome 10.0 SCN8A SCN2A
13 childhood electroclinical syndrome 10.0 SCN8A SCN2A
14 benign neonatal seizures 10.0 SCN8A SCN2A
15 paroxysmal extreme pain disorder 10.0 SCN8A SCN2A
16 alpha-thalassemia 10.0 SMARCA4 SCN2A H2AC18
17 neonatal period electroclinical syndrome 10.0 SCN8A SCN2A
18 blood protein disease 9.9 SCN2A H2AC18
19 epileptic encephalopathy, early infantile, 14 9.9 SMARCA4 SCN8A SCN2A
20 somatoform disorder 9.9 SCN8A H2AC18
21 non-syndromic intellectual disability 9.9 SMARCE1 SMARCA4 H2AC18 ARID2
22 rhabdoid cancer 9.8 SMARCE1 SMARCA4 H2AC18 ARID2
23 cartilage-hair hypoplasia 9.8 SMARCA4 H2AC18
24 pervasive developmental disorder 9.7 SCN8A SCN2A H2AC18
25 migraine with or without aura 1 9.7 SCN8A SCN2A H2AC18
26 coffin-siris syndrome 3 9.4 SMARCE1 PALM H2AC18 CMAS ARID2
27 coffin-siris syndrome 2 8.9 SMARCE1 IK H2AC18 CNDP2 CMAS ARID2
28 coffin-siris syndrome 1 8.1 SMARCE1 SMARCA4 SLC44A3 PALM IK H2AC18
29 autosomal dominant non-syndromic intellectual disability 7.7 SMARCE1 SMARCA4 SFMBT1 SCN8A SCN2A IK

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 microcephaly 31 very rare (1%) HP:0000252
2 visual impairment 31 very rare (1%) HP:0000505
3 thick eyebrow 31 very rare (1%) HP:0000574
4 dandy-walker malformation 31 very rare (1%) HP:0001305
5 sparse scalp hair 31 very rare (1%) HP:0002209
6 long eyelashes 31 very rare (1%) HP:0000527
7 hirsutism 31 very rare (1%) HP:0001007
8 seizure 31 very rare (1%) HP:0001250
9 macroglossia 31 HP:0000158
10 coarse facial features 31 HP:0000280
11 hearing impairment 31 HP:0000365
12 intellectual disability 31 HP:0001249
13 global developmental delay 31 HP:0001263
14 delayed skeletal maturation 31 HP:0002750
15 depressed nasal bridge 31 HP:0005280
16 scoliosis 31 HP:0002650
17 anteverted nares 31 HP:0000463
18 short stature 31 HP:0004322
19 feeding difficulties 31 HP:0011968
20 thick nasal alae 31 HP:0009928
21 intrauterine growth retardation 31 HP:0001511
22 wide mouth 31 HP:0000154
23 wide nose 31 HP:0000445
24 abnormality of cardiovascular system morphology 31 HP:0030680
25 abnormal heart morphology 31 HP:0001627
26 generalized hypotonia 31 HP:0001290
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
Head And Neck Mouth:
macroglossia
large mouth
thin upper vermilion
thick lower vermilion

Skeletal Spine:
scoliosis

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

Abdomen Gastrointestinal:
feeding problems

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

Head And Neck Head:
microcephaly (in some patients)

Head And Neck Ears:
hearing impairment

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

Head And Neck Teeth:
delayed dentition

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

Skin Nails Hair Nails:
hypoplastic or absent nails

Clinical features from OMIM:

614609

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased Nanog expression GR00371-A-1 9.1 SMARCE1
2 Increased Nanog expression GR00371-A-2 9.1 ARID2 SFMBT1 SMARCE1
3 Increased Nanog expression GR00371-A-3 9.1 ARID2
4 Increased Nanog expression GR00371-A-5 9.1 SFMBT1

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
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. 6 56
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.2851G>A (p.Gly951Arg)SNV Pathogenic 403671 rs1060499936 19:11132635-11132635 19:11021959-11021959
2 SMARCA4 NM_003072.5(SMARCA4):c.1675G>A (p.Glu559Lys)SNV Pathogenic 807689 19:11106970-11106970 19:10996294-10996294
3 SMARCA4 NM_003072.4(SMARCA4):c.1633_1635AAG[1] (p.Lys546del)short repeat Pathogenic 30342 rs876657378 19:11106926-11106928 19:10996250-10996252
4 SMARCA4 NM_003072.4(SMARCA4):c.2576C>T (p.Thr859Met)SNV Pathogenic 30343 rs281875226 19:11130337-11130337 19:11019661-11019661
5 SMARCA4 NM_003072.4(SMARCA4):c.2653C>T (p.Arg885Cys)SNV Pathogenic 30344 rs281875227 19:11132437-11132437 19:11021761-11021761
6 SMARCA4 NM_003072.4(SMARCA4):c.2761C>T (p.Leu921Phe)SNV Pathogenic 30345 rs281875228 19:11132545-11132545 19:11021869-11021869
7 SMARCA4 NM_003072.4(SMARCA4):c.3032T>C (p.Met1011Thr)SNV Pathogenic 30346 rs281875229 19:11135065-11135065 19:11024389-11024389
8 SMARCA4 NM_003072.4(SMARCA4):c.3469C>G (p.Arg1157Gly)SNV Pathogenic 30347 rs281875230 19:11141492-11141492 19:11030816-11030816
9 SMARCA4 NM_003072.4(SMARCA4):c.3922C>T (p.Arg1308Trp)SNV Likely pathogenic 126361 rs587779750 19:11144847-11144847 19:11034171-11034171
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_003072.5(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_001128849.2(SMARCA4):c.3127C>T (p.Arg1043Trp)SNV Likely pathogenic 436813 rs770014321 19:11136143-11136143 19:11025467-11025467
14 SMARCA4 NM_001128849.2(SMARCA4):c.3608G>A (p.Arg1203His)SNV Conflicting interpretations of pathogenicity 449452 rs770680174 19:11144027-11144027 19:11033351-11033351
15 SMARCA4 NM_001128849.2(SMARCA4):c.3557C>T (p.Ala1186Val)SNV Conflicting interpretations of pathogenicity 657828 19:11143976-11143976 19:11033300-11033300
16 SMARCA4 NM_001128849.2(SMARCA4):c.2704G>A (p.Val902Met)SNV Conflicting interpretations of pathogenicity 689790 19:11132488-11132488 19:11021812-11021812
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.1018G>A (p.Ala340Thr)SNV Uncertain significance 238356 rs371214327 19:11098500-11098500 19:10987824-10987824
20 SMARCA4 NM_001128849.2(SMARCA4):c.3436G>A (p.Gly1146Ser)SNV Uncertain significance 238428 rs200007170 19:11141459-11141459 19:11030783-11030783
21 SMARCA4 NM_001128849.2(SMARCA4):c.4351G>A (p.Ala1451Thr)SNV Uncertain significance 238467 rs374722116 19:11152067-11152067 19:11041391-11041391
22 SMARCA4 NM_001128849.2(SMARCA4):c.4913A>G (p.Gln1638Arg)SNV Uncertain significance 238491 rs878854231 19:11170769-11170769 19:11060093-11060093
23 SMARCA4 NM_001128849.2(SMARCA4):c.422C>T (p.Ser141Leu)SNV Uncertain significance 408627 rs1060502073 19:11096931-11096931 19:10986255-10986255
24 SMARCA4 NM_001128849.2(SMARCA4):c.952G>A (p.Val318Ile)SNV Uncertain significance 408669 rs758091260 19:11098434-11098434 19:10987758-10987758
25 SMARCA4 NM_001128849.2(SMARCA4):c.4967C>T (p.Pro1656Leu)SNV Uncertain significance 408631 rs756255060 19:11170823-11170823 19:11060147-11060147
26 SMARCA4 NM_001128849.2(SMARCA4):c.4972G>A (p.Val1658Met)SNV Uncertain significance 408703 rs757412819 19:11170828-11170828 19:11060152-11060152
27 SMARCA4 NM_001128849.2(SMARCA4):c.1889G>A (p.Gly630Asp)SNV Uncertain significance 408664 rs749533909 19:11113781-11113781 19:11003105-11003105
28 SMARCA4 NM_001128849.2(SMARCA4):c.778A>C (p.Met260Leu)SNV Uncertain significance 422533 rs1064795842 19:11097598-11097598 19:10986922-10986922
29 SMARCA4 NM_001128849.2(SMARCA4):c.4520+6C>TSNV Uncertain significance 470402 rs778283753 19:11152242-11152242 19:11041566-11041566
30 SMARCA4 NM_001128849.2(SMARCA4):c.407C>T (p.Ala136Val)SNV Uncertain significance 470381 rs535299273 19:11096916-11096916 19:10986240-10986240
31 SMARCA4 NM_001128849.2(SMARCA4):c.709G>A (p.Gly237Ser)SNV Uncertain significance 470453 rs1555753727 19:11097218-11097218 19:10986542-10986542
32 SMARCA4 NM_001128849.2(SMARCA4):c.914C>T (p.Pro305Leu)SNV Uncertain significance 470468 rs138097741 19:11098396-11098396 19:10987720-10987720
33 SMARCA4 NM_001128849.2(SMARCA4):c.4922T>C (p.Leu1641Pro)SNV Uncertain significance 470424 rs755493468 19:11170778-11170778 19:11060102-11060102
34 SMARCA4 NM_001128849.2(SMARCA4):c.829C>T (p.Pro277Ser)SNV Uncertain significance 480580 rs767947665 19:11097649-11097649 19:10986973-10986973
35 SMARCA4 NM_001128849.2(SMARCA4):c.1098C>G (p.Ile366Met)SNV Uncertain significance 484848 rs532242119 19:11098580-11098580 19:10987904-10987904
36 SMARCA4 NM_001128849.2(SMARCA4):c.1108C>T (p.Arg370Cys)SNV Uncertain significance 480659 rs1436490540 19:11098590-11098590 19:10987914-10987914
37 SMARCA4 NM_001128849.2(SMARCA4):c.4472C>T (p.Thr1491Ile)SNV Uncertain significance 537775 rs1555788341 19:11152188-11152188 19:11041512-11041512
38 SMARCA4 NM_001128849.2(SMARCA4):c.2438+4A>CSNV Uncertain significance 572876 rs771818596 19:11123792-11123792 19:11013116-11013116

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
12.1 SMARCE1 SMARCA4 H2AC18 ARID2
2 10.1 SCN8A 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 nucleoplasm GO:0005654 9.97 SMARCE1 SMARCA4 SFMBT1 PALM IK CNDP2
2 SWI/SNF complex GO:0016514 9.32 SMARCE1 SMARCA4
3 voltage-gated sodium channel complex GO:0001518 9.26 SCN8A SCN2A
4 nBAF complex GO:0071565 9.16 SMARCE1 SMARCA4
5 node of Ranvier GO:0033268 8.96 SCN8A SCN2A
6 npBAF complex GO:0071564 8.62 SMARCE1 SMARCA4

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

# Name GO ID Score Top Affiliating Genes
1 nervous system development GO:0007399 9.62 SMARCE1 SMARCA4 SCN8A SCN2A
2 ATP-dependent chromatin remodeling GO:0043044 9.37 SMARCE1 SMARCA4
3 chromatin organization GO:0006325 9.35 SMARCE1 SMARCA4 SFMBT1 H2AC18 ARID2
4 neuronal action potential GO:0019228 9.26 SCN8A SCN2A
5 membrane depolarization during action potential GO:0086010 9.16 SCN8A SCN2A
6 nucleosome disassembly GO:0006337 8.8 SMARCE1 SMARCA4 ARID2

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

# Name GO ID Score Top Affiliating Genes
1 cation channel activity GO:0005261 9.26 SCN8A SCN2A
2 nucleosomal DNA binding GO:0031492 9.16 SMARCE1 SMARCA4
3 sodium channel activity GO:0005272 8.96 SCN8A SCN2A
4 voltage-gated sodium channel activity GO:0005248 8.62 SCN8A 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
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43 MeSH
44 MESH via Orphanet
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48 NCI
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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
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