COFS4
MCID: CRB100
MIFTS: 33

Cerebrooculofacioskeletal Syndrome 4 (COFS4)

Categories: Bone diseases, Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Cerebrooculofacioskeletal Syndrome 4

MalaCards integrated aliases for Cerebrooculofacioskeletal Syndrome 4:

Name: Cerebrooculofacioskeletal Syndrome 4 57 29 13 6 70
Cofs4 57 72
Cerebrooculofacioskeletal Syndrome, Type 4 39
Cerebro-Oculo-Facio-Skeletal Syndrome 4 72
Cofs Syndrome 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

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


HPO:

31
cerebrooculofacioskeletal syndrome 4:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:



Summaries for Cerebrooculofacioskeletal Syndrome 4

OMIM® : 57 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) (Updated 05-Apr-2021)

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 eye and bone, and related phenotypes are hyperreflexia and eeg abnormality

UniProtKB/Swiss-Prot : 72 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

Graphical network of the top 20 diseases related to Cerebrooculofacioskeletal Syndrome 4:



Diseases related to Cerebrooculofacioskeletal Syndrome 4

Symptoms & Phenotypes for Cerebrooculofacioskeletal Syndrome 4

Human phenotypes related to Cerebrooculofacioskeletal Syndrome 4:

31 (show all 30)
# Description HPO Frequency HPO Source Accession
1 hyperreflexia 31 HP:0001347
2 eeg abnormality 31 HP:0002353
3 nystagmus 31 HP:0000639
4 global developmental delay 31 HP:0001263
5 microcephaly 31 HP:0000252
6 short stature 31 HP:0004322
7 hypertonia 31 HP:0001276
8 intrauterine growth retardation 31 HP:0001511
9 micrognathia 31 HP:0000347
10 failure to thrive in infancy 31 HP:0001531
11 slender long bone 31 HP:0003100
12 kyphoscoliosis 31 HP:0002751
13 low-set, posteriorly rotated ears 31 HP:0000368
14 deeply set eye 31 HP:0000490
15 hip dislocation 31 HP:0002827
16 prominent nasal bridge 31 HP:0000426
17 short philtrum 31 HP:0000322
18 blepharophimosis 31 HP:0000581
19 adducted thumb 31 HP:0001181
20 arthrogryposis multiplex congenita 31 HP:0002804
21 flexion contracture of toe 31 HP:0005830
22 camptodactyly of finger 31 HP:0100490
23 polymicrogyria 31 HP:0002126
24 cerebellar hypoplasia 31 HP:0001321
25 rocker bottom foot 31 HP:0001838
26 dislocated radial head 31 HP:0003083
27 flared metaphysis 31 HP:0003015
28 premature closure of fontanelles 31 HP:0005458
29 simplified gyral pattern 31 HP:0009879
30 bilateral microphthalmos 31 HP:0007633

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Peripheral Nervous System:
hyperreflexia

Head And Neck Head:
microcephaly

Growth Other:
intrauterine growth retardation
poor growth

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

Skeletal Pelvis:
hip dislocation
sloping acetabulae

Skeletal Hands:
camptodactyly
adducted thumbs

Skeletal:
joint contractures
arthrogryposis

Skeletal Skull:
premature closure of fontanels

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

Neurologic Central Nervous System:
hypertonia
polymicrogyria
cerebellar hypoplasia
simplified gyral pattern
stiff limbs
more
Head And Neck Face:
micrognathia
short philtrum

Skeletal Spine:
kyphoscoliosis

Skeletal Limbs:
dislocated radial head
slender long bones
flared metaphyses

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 (Updated 05-Apr-2021)

UMLS symptoms related to Cerebrooculofacioskeletal Syndrome 4:


stiff limbs

MGI Mouse Phenotypes related to Cerebrooculofacioskeletal Syndrome 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hearing/vestibular/ear MP:0005377 8.62 ERCC1 POLR1G

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 29 ERCC1

Anatomical Context for Cerebrooculofacioskeletal Syndrome 4

MalaCards organs/tissues related to Cerebrooculofacioskeletal Syndrome 4:

40
Eye, Bone

Publications for Cerebrooculofacioskeletal Syndrome 4

Articles related to Cerebrooculofacioskeletal Syndrome 4:

(show all 42)
# Title Authors PMID Year
1
Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and Fanconi anemia. 6 57
23623389 2013
2
First reported patient with human ERCC1 deficiency has cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure. 6 57
17273966 2007
3
Cerebro-oculo-facio-skeletal syndrome caused by the homozygous pathogenic variant Gly47Arg in ERCC2. 61
33369099 2021
4
Prenatal findings of cataract and arthrogryposis: recurrence of cerebro-oculo-facio-skeletal syndrome and review of differential diagnosis. 61
33766032 2021
5
COFS type 3 in an Indian family with antenatally detected arthrogryposis. 61
33219753 2021
6
Prenatal diagnosis of cerebro-oculo-facio-skeletal syndrome: Report of three fetuses and review of the literature. 61
32052936 2020
7
Oxidative and energy metabolism as potential clues for clinical heterogeneity in nucleotide excision repair disorders. 61
25296907 2015
8
Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency. 61
25299392 2014
9
Dermatologic findings in 16 patients with Cockayne syndrome and cerebro-oculo-facial-skeletal syndrome. 61
24154677 2013
10
Cockayne syndrome: the expanding clinical and mutational spectrum. 61
23428416 2013
11
Disease-causing missense mutations in human DNA helicase disorders. 61
23276657 2013
12
DNA helicases associated with genetic instability, cancer, and aging. 61
23161009 2013
13
ERCC6 founder mutation identified in Finnish patients with COFS syndrome. 61
20456449 2010
14
Cerebro-oculo-facio-skeletal syndrome. 61
20687508 2010
15
Magnetic resonance imaging of the fetal central nervous system in Singapore. 61
19816636 2009
16
Café au lait macules and cerebro-oculo-facio-skeletal syndrome: a novel association. 61
19250421 2009
17
Cerebro-oculo-facio-skeletal syndrome: three additional cases with CSB mutations, new diagnostic criteria and an approach to investigation. 61
18628313 2008
18
Cerebro-oculo-facio-skeletal (COFS) syndrome in siblings. 61
15630331 2004
19
MICRO syndrome: an entity distinct from COFS syndrome. 61
15216543 2004
20
Cerebro-oculo-facio-skeletal syndrome: report of two cases from Turkey with postmortem findings. 61
12405446 2002
21
Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair defect and a mutated XPD gene, with prenatal diagnosis in a triplet pregnancy. 61
11443545 2001
22
Cerebro-oculo-facio-skeletal syndrome as a human example for accelerated cochlear nerve degeneration. 61
11300264 2001
23
[Cerebro-oculo-facio-skeletal (COFS) syndrome]. 61
11462474 2001
24
Cockayne Syndrome 61
20301516 2000
25
Prenatal diagnosis of the cerebro-oculo-facio-skeletal (COFS) syndrome. 61
11084975 2000
26
Manitoba aboriginal kindred with original cerebro-oculo- facio-skeletal syndrome has a mutation in the Cockayne syndrome group B (CSB) gene. 61
10739753 2000
27
[Cerebro-oculo-facio-skeletal (COFS) syndrome]. 61
11057139 2000
28
Microcephaly, microphthalmia, congenital cataract, with calcification of the basal ganglia: MCA/MR syndrome. 61
11140418 2000
29
Neuropathological findings in eight children with cerebro-oculo-facio-skeletal (COFS) syndrome. 61
9329459 1997
30
Restrictive dermopathy: report and review. 61
9217218 1997
31
COFS syndrome with familial 1;16 translocation. 61
9001808 1996
32
Xeroderma pigmentosum--Cockayne syndrome complex: a further case. 61
8818951 1996
33
[Bilateral vocal cord paralysis in children]. 61
8822258 1996
34
Cerebro-oculo-facio-skeletal syndrome: further delineation. 61
1951466 1991
35
Infantile spasms in COFS syndrome. 61
1930425 1991
36
Cerebro-oculo-facio-skeletal (COFS) syndrome. The variability of presenting symptoms as a manifestation of two subtypes? 61
1741976 1991
37
Early onset Cockayne's syndrome: case reports with neuropathological and fibroblast studies. 61
2468771 1989
38
Chondro-osseous changes in Cerebro-Oculo-Facial-Skeletal (COFS) syndrome. 61
7153815 1982
39
Intracranial calcifications in cerebro-oculo-facio-skeletal (COFS) syndrome. 61
7063265 1982
40
COFS syndrome revisited. 61
728562 1978
41
Further evidence for the autosomal-recessive inheritance of the COFS syndrome. 61
825334 1976
42
Autosomal recessive cerebro-oculo-facio-skeletal (COFS) syndrome. 61
4211825 1974

Variations for Cerebrooculofacioskeletal Syndrome 4

ClinVar genetic disease variations for Cerebrooculofacioskeletal Syndrome 4:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ERCC1 NM_001983.4(ERCC1):c.472C>T (p.Gln158Ter) SNV Pathogenic 16777 rs121913027 GRCh37: 19:45922409-45922409
GRCh38: 19:45419151-45419151
2 ERCC1 NM_001983.4(ERCC1):c.693C>G (p.Phe231Leu) SNV Pathogenic 16778 rs121913028 GRCh37: 19:45918128-45918128
GRCh38: 19:45414870-45414870
3 ERCC1 NM_001983.4(ERCC1):c.184G>T (p.Glu62Ter) SNV Likely pathogenic 225348 rs150584960 GRCh37: 19:45924573-45924573
GRCh38: 19:45421315-45421315
4 ERCC1 NM_001983.4(ERCC1):c.796G>A (p.Ala266Thr) SNV Uncertain significance 592147 rs3212977 GRCh37: 19:45916982-45916982
GRCh38: 19:45413724-45413724
5 ERCC1 NM_001983.4(ERCC1):c.799T>C (p.Ser267Pro) SNV Uncertain significance 638523 rs146256515 GRCh37: 19:45916979-45916979
GRCh38: 19:45413721-45413721
6 ERCC1 , POLR1G NM_001983.4(ERCC1):c.*863T>C SNV Benign 235480 rs3212989 GRCh37: 19:45912070-45912070
GRCh38: 19:45408812-45408812

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

72
# Symbol AA change Variation ID SNP ID
1 ERCC1 p.Phe231Leu VAR_032776 rs121913028

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
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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