CSS3
MCID: CFF010
MIFTS: 34

Coffin-Siris Syndrome 3 (CSS3)

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

Aliases & Classifications for Coffin-Siris Syndrome 3

MalaCards integrated aliases for Coffin-Siris Syndrome 3:

Name: Coffin-Siris Syndrome 3 58 12 76 15
Mental Retardation, Autosomal Dominant 15 58 76 30 13 6 74
Mrd15 58 12 76
Css3 58 12 76
Mental Retardation, Autosomal Dominant 15; Mrd15 58
Autosomal Dominant Mental Retardation 15 12
Coffin-Siris Syndrome, Type 3 ) 41
Coffin-Siris Syndrome, Type 3 41

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant


HPO:

33
coffin-siris syndrome 3:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Coffin-Siris Syndrome 3

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 SMARCB1 mutations may have more severe neurodevelopmental deficits including severe intellectual disability, brain structural abnormalities, and no expressive words, as well as scoliosis (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900). (614608)

MalaCards based summary : Coffin-Siris Syndrome 3, also known as mental retardation, autosomal dominant 15, is related to coffin-siris syndrome 1 and autosomal dominant non-syndromic intellectual disability, and has symptoms including seizures An important gene associated with Coffin-Siris Syndrome 3 is SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1). Affiliated tissues include brain, 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 SMARCB1 on chromosome 22q11.23.

UniProtKB/Swiss-Prot : 76 Coffin-Siris syndrome 3: 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.

Related Diseases for Coffin-Siris Syndrome 3

Diseases in the Coffin-Siris Syndrome 1 family:

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

Diseases related to Coffin-Siris Syndrome 3 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 coffin-siris syndrome 1 9.6 CHPF2 CHSY1 SMARCB1
2 autosomal dominant non-syndromic intellectual disability 9.5 CHPF2 CHSY1 SMARCB1

Symptoms & Phenotypes for Coffin-Siris Syndrome 3

Human phenotypes related to Coffin-Siris Syndrome 3:

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 cerebellar hypoplasia 33 very rare (1%) HP:0001321
4 hirsutism 33 very rare (1%) HP:0001007
5 intellectual disability 33 HP:0001249
6 scoliosis 33 HP:0002650
7 macroglossia 33 HP:0000158
8 coarse facial features 33 HP:0000280
9 hearing impairment 33 HP:0000365
10 global developmental delay 33 HP:0001263
11 delayed skeletal maturation 33 HP:0002750
12 depressed nasal bridge 33 HP:0005280
13 anteverted nares 33 HP:0000463
14 visual impairment 33 HP:0000505
15 thick eyebrow 33 HP:0000574
16 short stature 33 HP:0004322
17 feeding difficulties 33 HP:0011968
18 intrauterine growth retardation 33 HP:0001511
19 wide mouth 33 HP:0000154
20 sparse scalp hair 33 HP:0002209
21 long eyelashes 33 HP:0000527
22 wide nose 33 HP:0000445
23 generalized hypotonia 33 HP:0001290
24 abnormality of cardiovascular system morphology 33 HP:0030680
25 hypertrichosis 33 HP:0000998
26 delayed eruption of permanent teeth 33 HP:0000696
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
Neurologic Central Nervous System:
seizures
hypotonia
mental retardation
delayed psychomotor development, severe
small cerebellum
more
Head And Neck Mouth:
macroglossia
large mouth
thin upper vermilion
thick lower vermilion

Head And Neck Head:
microcephaly

Growth Height:
short stature

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)

Skeletal Spine:
scoliosis

Head And Neck Ears:
hearing impairment

Head And Neck Eyes:
visual impairment
long eyelashes
thick eyebrows

Growth Other:
intrauterine growth retardation
poor overall growth

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

Head And Neck Face:
coarse facies

Head And Neck Teeth:
delayed dentition

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

Skin Nails Hair Nails:
hypoplastic or absent nails

Clinical features from OMIM:

614608

UMLS symptoms related to Coffin-Siris Syndrome 3:


seizures

MGI Mouse Phenotypes related to Coffin-Siris Syndrome 3:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.02 ALDH1B1 B4GALNT1 CHSY1 SMARCB1 SRCIN1

Drugs & Therapeutics for Coffin-Siris Syndrome 3

Search Clinical Trials , NIH Clinical Center for Coffin-Siris Syndrome 3

Genetic Tests for Coffin-Siris Syndrome 3

Genetic tests related to Coffin-Siris Syndrome 3:

# Genetic test Affiliating Genes
1 Mental Retardation, Autosomal Dominant 15 30 SMARCB1

Anatomical Context for Coffin-Siris Syndrome 3

MalaCards organs/tissues related to Coffin-Siris Syndrome 3:

42
Brain, Bone, Heart, Cerebellum

Publications for Coffin-Siris Syndrome 3

Articles related to Coffin-Siris Syndrome 3:

# Title Authors Year
1
Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. ( 22426308 )
2012
2
Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability. ( 22726846 )
2012

Variations for Coffin-Siris Syndrome 3

UniProtKB/Swiss-Prot genetic disease variations for Coffin-Siris Syndrome 3:

76
# Symbol AA change Variation ID SNP ID
1 SMARCB1 p.Arg377His VAR_068179 rs387906812
2 SMARCB1 p.Arg366Cys VAR_076934 rs886039520
3 SMARCB1 p.Arg374Gln VAR_076935 rs105751782

ClinVar genetic disease variations for Coffin-Siris Syndrome 3:

6 (show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 SMARCB1 NM_003073.4(SMARCB1): c.1091_1093delAGA (p.Lys364del) deletion Pathogenic/Likely pathogenic rs875989800 GRCh38 Chromosome 22, 23833676: 23833678
2 SMARCB1 NM_003073.4(SMARCB1): c.1091_1093delAGA (p.Lys364del) deletion Pathogenic/Likely pathogenic rs875989800 GRCh37 Chromosome 22, 24175863: 24175865
3 SMARCB1 NM_003073.4(SMARCB1): c.1130G> A (p.Arg377His) single nucleotide variant Pathogenic rs387906812 GRCh37 Chromosome 22, 24176339: 24176339
4 SMARCB1 NM_003073.4(SMARCB1): c.1130G> A (p.Arg377His) single nucleotide variant Pathogenic rs387906812 GRCh38 Chromosome 22, 23834152: 23834152
5 SMARCB1 NM_003073.4(SMARCB1): c.110G> A (p.Arg37His) single nucleotide variant Conflicting interpretations of pathogenicity rs398122368 GRCh37 Chromosome 22, 24133959: 24133959
6 SMARCB1 NM_003073.4(SMARCB1): c.110G> A (p.Arg37His) single nucleotide variant Conflicting interpretations of pathogenicity rs398122368 GRCh38 Chromosome 22, 23791772: 23791772
7 SMARCB1 NM_003073.4(SMARCB1): c.1087A> G (p.Lys363Glu) single nucleotide variant Likely pathogenic rs797045989 GRCh38 Chromosome 22, 23833672: 23833672
8 SMARCB1 NM_003073.4(SMARCB1): c.1087A> G (p.Lys363Glu) single nucleotide variant Likely pathogenic rs797045989 GRCh37 Chromosome 22, 24175859: 24175859
9 SMARCB1 NM_003073.4(SMARCB1): c.602G> A (p.Arg201Gln) single nucleotide variant Likely pathogenic rs1555877287 GRCh37 Chromosome 22, 24145583: 24145583
10 SMARCB1 NM_003073.4(SMARCB1): c.602G> A (p.Arg201Gln) single nucleotide variant Likely pathogenic rs1555877287 GRCh38 Chromosome 22, 23803396: 23803396
11 SMARCB1 NM_003073.4(SMARCB1): c.1070C> G (p.Thr357Arg) single nucleotide variant Likely pathogenic rs1555881567 GRCh38 Chromosome 22, 23833655: 23833655
12 SMARCB1 NM_003073.4(SMARCB1): c.1070C> G (p.Thr357Arg) single nucleotide variant Likely pathogenic rs1555881567 GRCh37 Chromosome 22, 24175842: 24175842
13 SMARCB1 NM_003073.4(SMARCB1): c.1089G> T (p.Lys363Asn) single nucleotide variant Uncertain significance GRCh37 Chromosome 22, 24175861: 24175861
14 SMARCB1 NM_003073.4(SMARCB1): c.1089G> T (p.Lys363Asn) single nucleotide variant Uncertain significance GRCh38 Chromosome 22, 23833674: 23833674

Expression for Coffin-Siris Syndrome 3

Search GEO for disease gene expression data for Coffin-Siris Syndrome 3.

Pathways for Coffin-Siris Syndrome 3

GO Terms for Coffin-Siris Syndrome 3

Cellular components related to Coffin-Siris Syndrome 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi membrane GO:0000139 9.13 B4GALNT1 CHPF2 CHSY1
2 Golgi cisterna membrane GO:0032580 8.62 CHPF2 CHSY1

Biological processes related to Coffin-Siris Syndrome 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 carbohydrate metabolic process GO:0005975 8.96 ALDH1B1 B4GALNT1
2 chondroitin sulfate biosynthetic process GO:0030206 8.62 CHPF2 CHSY1

Molecular functions related to Coffin-Siris Syndrome 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity GO:0050510 8.96 CHPF2 CHSY1
2 acetylgalactosaminyltransferase activity GO:0008376 8.8 B4GALNT1 CHPF2 CHSY1

Sources for Coffin-Siris Syndrome 3

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
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
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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