CSS2
MCID: CFF007
MIFTS: 30

Coffin-Siris Syndrome 2 (CSS2)

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

Aliases & Classifications for Coffin-Siris Syndrome 2

MalaCards integrated aliases for Coffin-Siris Syndrome 2:

Name: Coffin-Siris Syndrome 2 57 12 75 15
Mental Retardation, Autosomal Dominant 14 57 75 29 13 6 73
Mrd14 57 12 75
Css2 57 12 75
Mental Retardation, Autosomal Dominant 14; Mrd14 57
Autosomal Dominant Mental Retardation 14 12
Coffin-Siris Syndrome, Type 2 ) 40

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
coffin-siris syndrome 2:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Coffin-Siris Syndrome 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 ARID1A mutations have a wide spectrum of manifestations, from severe intellectual disability and serious internal complications that could result in early death to mild intellectual disability (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900). The chromosome 1p36.11 duplication syndrome, in which the ARID1A gene is duplicated, is characterized by impaired intellectual development, microcephaly, dysmorphic facial features, and hand and foot anomalies. (614607)

MalaCards based summary : Coffin-Siris Syndrome 2, also known as mental retardation, autosomal dominant 14, is related to coffin-siris syndrome 1 and autosomal dominant non-syndromic intellectual disability. An important gene associated with Coffin-Siris Syndrome 2 is ARID1A (AT-Rich Interaction Domain 1A). 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 ARID1A on chromosome 1p36.11.

UniProtKB/Swiss-Prot : 75 Coffin-Siris syndrome 2: 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 2

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

Diseases related to Coffin-Siris Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 coffin-siris syndrome 1 9.6 ARID1A CHSY1 CRYBB1
2 autosomal dominant non-syndromic intellectual disability 9.4 ARID1A ARL6IP6 CHSY1 CNDP2

Symptoms & Phenotypes for Coffin-Siris Syndrome 2

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Mouth:
macroglossia
large mouth
thin upper vermilion
thick lower vermilion

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

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

Neurologic Central Nervous System:
hypotonia
mental retardation
delayed psychomotor development
seizures (in some patients)
speech delay
more
Head And Neck Face:
coarse facies

Head And Neck Ears:
malformed ears

Head And Neck Teeth:
delayed dentition

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

Head And Neck Eyes:
visual impairment
long eyelashes
thick eyebrows

Skin Nails Hair Hair:
sparse scalp hair
hypertrichosis
low frontal hairline

Skin Nails Hair Nails:
hypoplastic nails

Skeletal:
delayed bone age

Cardiovascular Heart:
congenital heart defects

Growth Height:
short stature (in some patients)

Abdomen Gastrointestinal:
feeding problems


Clinical features from OMIM:

614607

Human phenotypes related to Coffin-Siris Syndrome 2:

32 (show all 30)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 32 HP:0001249
2 seizures 32 occasional (7.5%) HP:0001250
3 macroglossia 32 HP:0000158
4 coarse facial features 32 very rare (1%) HP:0000280
5 global developmental delay 32 HP:0001263
6 delayed skeletal maturation 32 HP:0002750
7 depressed nasal bridge 32 HP:0005280
8 delayed speech and language development 32 HP:0000750
9 anteverted nares 32 HP:0000463
10 visual impairment 32 HP:0000505
11 thick eyebrow 32 HP:0000574
12 short stature 32 occasional (7.5%) HP:0004322
13 feeding difficulties 32 very rare (1%) HP:0011968
14 thick lower lip vermilion 32 very rare (1%) HP:0000179
15 abnormality of the pinna 32 HP:0000377
16 wide mouth 32 very rare (1%) HP:0000154
17 small nail 32 HP:0001792
18 brachydactyly 32 HP:0001156
19 recurrent infections 32 very rare (1%) HP:0002719
20 sparse scalp hair 32 very rare (1%) HP:0002209
21 low anterior hairline 32 HP:0000294
22 long eyelashes 32 very rare (1%) HP:0000527
23 wide nose 32 HP:0000445
24 generalized hypotonia 32 HP:0001290
25 abnormality of cardiovascular system morphology 32 HP:0030680
26 hypertrichosis 32 HP:0000998
27 aplasia/hypoplasia of the distal phalanges of the hand 32 HP:0009835
28 abnormal corpus callosum morphology 32 very rare (1%) HP:0001273
29 absent fifth fingernail 32 very rare (1%) HP:0200104
30 absent fifth toenail 32 very rare (1%) HP:0200105

GenomeRNAi Phenotypes related to Coffin-Siris Syndrome 2 according to GeneCards Suite gene sharing:

26 (show all 15)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-113 10.16 CNDP2
2 Increased shRNA abundance (Z-score > 2) GR00366-A-114 10.16 ARID1A
3 Increased shRNA abundance (Z-score > 2) GR00366-A-140 10.16 CNDP2
4 Increased shRNA abundance (Z-score > 2) GR00366-A-147 10.16 CNDP2
5 Increased shRNA abundance (Z-score > 2) GR00366-A-168 10.16 ARID1A
6 Increased shRNA abundance (Z-score > 2) GR00366-A-176 10.16 ARID1A CNDP2
7 Increased shRNA abundance (Z-score > 2) GR00366-A-186 10.16 ARID1A CNDP2
8 Increased shRNA abundance (Z-score > 2) GR00366-A-190 10.16 ARID1A
9 Increased shRNA abundance (Z-score > 2) GR00366-A-29 10.16 CNDP2
10 Increased shRNA abundance (Z-score > 2) GR00366-A-3 10.16 CNDP2
11 Increased shRNA abundance (Z-score > 2) GR00366-A-43 10.16 ARID1A CNDP2
12 Increased shRNA abundance (Z-score > 2) GR00366-A-73 10.16 ARID1A
13 Increased shRNA abundance (Z-score > 2) GR00366-A-99 10.16 CNDP2
14 Increased Sindbis virus (SINV) infection GR00310-A-1 8.92 ARL6IP6 CRYBB1
15 Increased Sindbis virus (SINV) infection GR00310-A-2 8.92 ARL6IP6 CRYBB1

Drugs & Therapeutics for Coffin-Siris Syndrome 2

Search Clinical Trials , NIH Clinical Center for Coffin-Siris Syndrome 2

Genetic Tests for Coffin-Siris Syndrome 2

Genetic tests related to Coffin-Siris Syndrome 2:

# Genetic test Affiliating Genes
1 Mental Retardation, Autosomal Dominant 14 29 ARID1A

Anatomical Context for Coffin-Siris Syndrome 2

MalaCards organs/tissues related to Coffin-Siris Syndrome 2:

41
Bone, Heart

Publications for Coffin-Siris Syndrome 2

Variations for Coffin-Siris Syndrome 2

ClinVar genetic disease variations for Coffin-Siris Syndrome 2:

6 (show all 30)
# Gene Variation Type Significance SNP ID Assembly Location
1 ARID1A NM_006015.4(ARID1A): c.31_56del26 (p.Ser11Alafs) deletion Pathogenic rs797045262 GRCh38 Chromosome 1, 26696434: 26696459
2 ARID1A NM_006015.4(ARID1A): c.31_56del26 (p.Ser11Alafs) deletion Pathogenic rs797045262 GRCh37 Chromosome 1, 27022925: 27022950
3 ARID1A NM_006015.4(ARID1A): c.2758C> T (p.Gln920Ter) single nucleotide variant Pathogenic rs387906845 GRCh37 Chromosome 1, 27092737: 27092737
4 ARID1A NM_006015.4(ARID1A): c.2758C> T (p.Gln920Ter) single nucleotide variant Pathogenic rs387906845 GRCh38 Chromosome 1, 26766246: 26766246
5 ARID1A NM_006015.4(ARID1A): c.4003C> T (p.Arg1335Ter) single nucleotide variant Pathogenic rs387906846 GRCh37 Chromosome 1, 27100207: 27100207
6 ARID1A NM_006015.4(ARID1A): c.4003C> T (p.Arg1335Ter) single nucleotide variant Pathogenic rs387906846 GRCh38 Chromosome 1, 26773716: 26773716
7 ARID1A NM_006015.4(ARID1A): c.394delG (p.Val132Trpfs) deletion Pathogenic rs797045263 GRCh38 Chromosome 1, 26696797: 26696797
8 ARID1A NM_006015.4(ARID1A): c.394delG (p.Val132Trpfs) deletion Pathogenic rs797045263 GRCh37 Chromosome 1, 27023288: 27023288
9 ARID1A NM_006015.4(ARID1A): c.5138T> C (p.Leu1713Pro) single nucleotide variant Likely pathogenic rs797045264 GRCh38 Chromosome 1, 26779036: 26779036
10 ARID1A NM_006015.4(ARID1A): c.5138T> C (p.Leu1713Pro) single nucleotide variant Likely pathogenic rs797045264 GRCh37 Chromosome 1, 27105527: 27105527
11 ARID1A NM_006015.4(ARID1A): c.5965C> T (p.Arg1989Ter) single nucleotide variant Pathogenic rs879255270 GRCh38 Chromosome 1, 26779863: 26779863
12 ARID1A NM_006015.4(ARID1A): c.5965C> T (p.Arg1989Ter) single nucleotide variant Pathogenic rs879255270 GRCh37 Chromosome 1, 27106354: 27106354
13 ARID1A NM_006015.4(ARID1A): c.1113delG (p.Gln372Serfs) deletion Pathogenic rs875989848 GRCh38 Chromosome 1, 26697516: 26697516
14 ARID1A NM_006015.4(ARID1A): c.1113delG (p.Gln372Serfs) deletion Pathogenic rs875989848 GRCh37 Chromosome 1, 27024007: 27024007
15 ARID1A NM_006015.4(ARID1A): c.3679G> T (p.Glu1227Ter) single nucleotide variant Pathogenic rs875989849 GRCh37 Chromosome 1, 27099442: 27099442
16 ARID1A NM_006015.4(ARID1A): c.3679G> T (p.Glu1227Ter) single nucleotide variant Pathogenic rs875989849 GRCh38 Chromosome 1, 26772951: 26772951
17 ARID1A NM_006015.5(ARID1A): c.3999_4001dup (p.Gln1334_Arg1335insGln) duplication Likely benign rs570962335 GRCh37 Chromosome 1, 27100203: 27100205
18 ARID1A NM_006015.5(ARID1A): c.3999_4001dup (p.Gln1334_Arg1335insGln) duplication Likely benign rs570962335 GRCh38 Chromosome 1, 26773712: 26773714
19 ARID1A NM_006015.5(ARID1A): c.921_940del20 (p.Tyr308Argfs) deletion Pathogenic GRCh38 Chromosome 1, 26697324: 26697343
20 ARID1A NM_006015.5(ARID1A): c.921_940del20 (p.Tyr308Argfs) deletion Pathogenic GRCh37 Chromosome 1, 27023815: 27023834
21 ARID1A NM_006015.5(ARID1A): c.5164C> T (p.Arg1722Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 26779062: 26779062
22 ARID1A NM_006015.5(ARID1A): c.5164C> T (p.Arg1722Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 27105553: 27105553
23 ARID1A NM_006015.5(ARID1A): c.3702C> T (p.Gly1234=) single nucleotide variant Likely benign rs376672377 GRCh38 Chromosome 1, 26772974: 26772974
24 ARID1A NM_006015.5(ARID1A): c.3702C> T (p.Gly1234=) single nucleotide variant Likely benign rs376672377 GRCh37 Chromosome 1, 27099465: 27099465
25 ARID1A NM_006015.5(ARID1A): c.4860dup (p.Pro1621Thrfs) duplication Likely pathogenic GRCh37 Chromosome 1, 27101578: 27101578
26 ARID1A NM_006015.5(ARID1A): c.4860dup (p.Pro1621Thrfs) duplication Likely pathogenic GRCh38 Chromosome 1, 26775087: 26775087
27 ARID1A NM_006015.5(ARID1A): c.1348C> T (p.Gln450Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 27056352: 27056352
28 ARID1A NM_006015.5(ARID1A): c.1348C> T (p.Gln450Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 26729861: 26729861
29 ARID1A NM_006015.5(ARID1A): c.6134_6138del (p.Lys2045Argfs) deletion Pathogenic GRCh37 Chromosome 1, 27106522: 27106527
30 ARID1A NM_006015.5(ARID1A): c.6134_6138del (p.Lys2045Argfs) deletion Pathogenic GRCh38 Chromosome 1, 26780032: 26780036

Expression for Coffin-Siris Syndrome 2

Search GEO for disease gene expression data for Coffin-Siris Syndrome 2.

Pathways for Coffin-Siris Syndrome 2

GO Terms for Coffin-Siris Syndrome 2

Sources for Coffin-Siris Syndrome 2

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