COFS4
MCID: CRB100
MIFTS: 28

Cerebrooculofacioskeletal Syndrome 4 (COFS4)

Categories: Bone diseases, Genetic diseases, Neuronal diseases, Skin diseases

Aliases & Classifications for Cerebrooculofacioskeletal Syndrome 4

MalaCards integrated aliases for Cerebrooculofacioskeletal Syndrome 4:

Name: Cerebrooculofacioskeletal Syndrome 4 58 30 13 6 74
Cofs4 58 76
Cerebro-Oculo-Facio-Skeletal Syndrome 4 76
Cofs Syndrome 76

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset at birth
early death
two unrelated patients have been reported (last curated june 2013)


HPO:

33
cerebrooculofacioskeletal syndrome 4:
Onset and clinical course variable expressivity congenital onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Cerebrooculofacioskeletal Syndrome 4

OMIM : 58 Cerebrooculofacioskeletal syndrome-4 is a severe autosomal recessive disorder characterized by growth retardation, dysmorphic facial features, arthrogryposis, and neurologic abnormalities. Cellular studies show a defect in both transcription-coupled and global genome nucleotide excision repair (TC-NER and GG-NER) (summary by Jaspers et al., 2007 and Kashiyama et al., 2013). For a discussion of genetic heterogeneity of cerebrooculofacioskeletal syndrome, see 214150. (610758)

MalaCards based summary : Cerebrooculofacioskeletal Syndrome 4, also known as cofs4, is related to cerebro-oculo-facio-skeletal syndrome and cerebrooculofacioskeletal syndrome 1, and has symptoms including stiff limbs An important gene associated with Cerebrooculofacioskeletal Syndrome 4 is ERCC1 (ERCC Excision Repair 1, Endonuclease Non-Catalytic Subunit). Affiliated tissues include bone and eye, and related phenotypes are nystagmus and hyperreflexia

UniProtKB/Swiss-Prot : 76 Cerebro-oculo-facio-skeletal syndrome 4: A disorder of prenatal onset characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. COFS is considered to be part of the nucleotide-excision repair disorders spectrum that include also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome.

Related Diseases for Cerebrooculofacioskeletal Syndrome 4

Diseases in the Cerebrooculofacioskeletal Syndrome 1 family:

Cerebrooculofacioskeletal Syndrome 2 Cerebrooculofacioskeletal Syndrome 4
Cerebrooculofacioskeletal Syndrome 3

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

# Related Disease Score Top Affiliating Genes
1 cerebro-oculo-facio-skeletal syndrome 11.9
2 cerebrooculofacioskeletal syndrome 1 11.8
3 cerebrooculofacioskeletal syndrome 2 11.5
4 congenital intrauterine infection-like syndrome 11.1

Symptoms & Phenotypes for Cerebrooculofacioskeletal Syndrome 4

Human phenotypes related to Cerebrooculofacioskeletal Syndrome 4:

33 (show all 30)
# Description HPO Frequency HPO Source Accession
1 nystagmus 33 HP:0000639
2 hyperreflexia 33 HP:0001347
3 eeg abnormality 33 HP:0002353
4 global developmental delay 33 HP:0001263
5 microcephaly 33 HP:0000252
6 short stature 33 HP:0004322
7 hypertonia 33 HP:0001276
8 micrognathia 33 HP:0000347
9 intrauterine growth retardation 33 HP:0001511
10 failure to thrive in infancy 33 HP:0001531
11 arthrogryposis multiplex congenita 33 HP:0002804
12 kyphoscoliosis 33 HP:0002751
13 prominent nasal bridge 33 HP:0000426
14 hip dislocation 33 HP:0002827
15 cerebellar hypoplasia 33 HP:0001321
16 short philtrum 33 HP:0000322
17 deeply set eye 33 HP:0000490
18 low-set, posteriorly rotated ears 33 HP:0000368
19 blepharophimosis 33 HP:0000581
20 adducted thumb 33 HP:0001181
21 camptodactyly of finger 33 HP:0100490
22 flexion contracture of toe 33 HP:0005830
23 polymicrogyria 33 HP:0002126
24 rocker bottom foot 33 HP:0001838
25 slender long bone 33 HP:0003100
26 dislocated radial head 33 HP:0003083
27 flared metaphysis 33 HP:0003015
28 bilateral microphthalmos 33 HP:0007633
29 premature closure of fontanelles 33 HP:0005458
30 cortical gyral simplification 33 HP:0009879

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Ears:
low-set ears
posteriorly rotated ears

Neurologic Peripheral Nervous System:
hyperreflexia

Neurologic Central Nervous System:
hypertonia
cerebellar hypoplasia
polymicrogyria
developmental delay
abnormal eeg
more
Growth Other:
intrauterine growth retardation
poor growth

Skeletal Pelvis:
hip dislocation
sloping acetabulae

Skeletal Limbs:
dislocated radial head
slender long bones
flared metaphyses

Skeletal:
joint contractures
arthrogryposis

Skeletal Skull:
premature closure of fontanels

Head And Neck Eyes:
nystagmus
microphthalmia
blepharophimosis
deep-set eyes

Head And Neck Head:
microcephaly

Head And Neck Face:
micrognathia
short philtrum

Skeletal Spine:
kyphoscoliosis

Skeletal Hands:
camptodactyly
adducted thumbs

Head And Neck Nose:
high nasal bridge

Skeletal Feet:
rocker-bottom feet

Laboratory Abnormalities:
patient cells show a defect in transcription-coupled and global genome nucleotide excision repair

Clinical features from OMIM:

610758

UMLS symptoms related to Cerebrooculofacioskeletal Syndrome 4:


stiff limbs

Drugs & Therapeutics for Cerebrooculofacioskeletal Syndrome 4

Search Clinical Trials , NIH Clinical Center for Cerebrooculofacioskeletal Syndrome 4

Genetic Tests for Cerebrooculofacioskeletal Syndrome 4

Genetic tests related to Cerebrooculofacioskeletal Syndrome 4:

# Genetic test Affiliating Genes
1 Cerebrooculofacioskeletal Syndrome 4 30 ERCC1

Anatomical Context for Cerebrooculofacioskeletal Syndrome 4

MalaCards organs/tissues related to Cerebrooculofacioskeletal Syndrome 4:

42
Bone, Eye

Publications for Cerebrooculofacioskeletal Syndrome 4

Articles related to Cerebrooculofacioskeletal Syndrome 4:

(show all 13)
# Title Authors Year
1
ERCC6 founder mutation identified in Finnish patients with COFS syndrome. ( 20456449 )
2010
2
MICRO syndrome: an entity distinct from COFS syndrome. ( 15216543 )
2004
3
Cerebro-oculo-facio-skeletal (COFS) syndrome in siblings. ( 15630331 )
2004
4
Prenatal diagnosis of the cerebro-oculo-facio-skeletal (COFS) syndrome. ( 11084975 )
2000
5
Neuropathological findings in eight children with cerebro-oculo-facio-skeletal (COFS) syndrome. ( 9329459 )
1997
6
COFS syndrome with familial 1;16 translocation. ( 9001808 )
1996
7
Infantile spasms in COFS syndrome. ( 1930425 )
1991
8
Cerebro-oculo-facio-skeletal (COFS) syndrome. The variability of presenting symptoms as a manifestation of two subtypes? ( 1741976 )
1991
9
Chondro-osseous changes in Cerebro-Oculo-Facial-Skeletal (COFS) syndrome. ( 7153815 )
1982
10
Intracranial calcifications in cerebro-oculo-facio-skeletal (COFS) syndrome. ( 7063265 )
1982
11
COFS syndrome revisited. ( 728562 )
1978
12
Further evidence for the autosomal-recessive inheritance of the COFS syndrome. ( 825334 )
1976
13
Autosomal recessive cerebro-oculo-facio-skeletal (COFS) syndrome. ( 4211825 )
1974

Variations for Cerebrooculofacioskeletal Syndrome 4

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

76
# Symbol AA change Variation ID SNP ID
1 ERCC1 p.Phe231Leu VAR_032776 rs121913028

ClinVar genetic disease variations for Cerebrooculofacioskeletal Syndrome 4:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 ERCC1 NM_001983.3(ERCC1): c.472C> T (p.Gln158Ter) single nucleotide variant Pathogenic rs121913027 GRCh37 Chromosome 19, 45922409: 45922409
2 ERCC1 NM_001983.3(ERCC1): c.472C> T (p.Gln158Ter) single nucleotide variant Pathogenic rs121913027 GRCh38 Chromosome 19, 45419151: 45419151
3 ERCC1 NM_202001.2(ERCC1): c.693C> G (p.Phe231Leu) single nucleotide variant Pathogenic rs121913028 GRCh37 Chromosome 19, 45918128: 45918128
4 ERCC1 NM_202001.2(ERCC1): c.693C> G (p.Phe231Leu) single nucleotide variant Pathogenic rs121913028 GRCh38 Chromosome 19, 45414870: 45414870
5 ERCC1 NM_001166049.1(ERCC1): c.184G> T (p.Glu62Ter) single nucleotide variant Likely pathogenic rs150584960 GRCh38 Chromosome 19, 45421315: 45421315
6 ERCC1 NM_001166049.1(ERCC1): c.184G> T (p.Glu62Ter) single nucleotide variant Likely pathogenic rs150584960 GRCh37 Chromosome 19, 45924573: 45924573
7 ERCC1 NM_202001.2(ERCC1): c.796G> A (p.Ala266Thr) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 45413724: 45413724
8 ERCC1 NM_202001.2(ERCC1): c.796G> A (p.Ala266Thr) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 45916982: 45916982

Expression for Cerebrooculofacioskeletal Syndrome 4

Search GEO for disease gene expression data for Cerebrooculofacioskeletal Syndrome 4.

Pathways for Cerebrooculofacioskeletal Syndrome 4

GO Terms for Cerebrooculofacioskeletal Syndrome 4

Sources for Cerebrooculofacioskeletal Syndrome 4

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
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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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