MCID: CCK005
MIFTS: 42

Cockayne Syndrome, Type a

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

Aliases & Classifications for Cockayne Syndrome, Type a

Summaries for Cockayne Syndrome, Type a

OMIM : 54
Cockayne syndrome is characterized by abnormal and slow growth and development that becomes evident within the first few years after birth. 'Cachectic dwarfism' describes the outward appearance of afflicted individuals. Other features include cutaneous photosensitivity, thin, dry hair, a progeroid appearance, progressive pigmentary retinopathy, sensorineural hearing loss, dental caries, and a characteristic stance in the ambulatory patient. Patients often show disproportionately long limbs with large hands and feet, and flexion contractures of joints are usual skeletal features. Knee contractures result in a 'horse-riding stance.' There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. The mean age at death in reported cases is 12.5 years, although a few affected individuals have lived into their late teens or twenties. Remarkably, in striking contrast with xeroderma pigmentosum, patients with CS have no significant increase in skin cancer or infection (Nance and Berry, 1992). Lowry (1982) noted that there is an early-onset form of Cockayne syndrome in which patients may show abnormalities at birth and have a shorter survival. Lowry (1982) thus suggested that CS could be divided clinically into the more common type I, with classic CS symptoms that manifest within the first few years or life, and the less common type II, with more severe symptoms that manifest prenatally. Mallery et al. (1998) found no correlation between genotype and phenotype among 16 patients with CS of varying severities, and concluded that clinical differences were based on other genetic backgrounds or the intrauterine environment. (216400)

MalaCards based summary : Cockayne Syndrome, Type a, also known as cockayne syndrome type a, is related to uv-sensitive syndrome 2 and central sleep apnea, and has symptoms including optic atrophy, nystagmus and dysarthria. An important gene associated with Cockayne Syndrome, Type a is ERCC8 (ERCC Excision Repair 8, CSA Ubiquitin Ligase Complex Subunit), and among its related pathways/superpathways are Transcription-Coupled Nucleotide Excision Repair (TC-NER) and Chks in Checkpoint Regulation. Affiliated tissues include skin and bone, and related phenotypes are Increased viability with MLN4924 (a NAE inhibitor) and hearing/vestibular/ear

UniProtKB/Swiss-Prot : 71 Cockayne syndrome A: A rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer.

Related Diseases for Cockayne Syndrome, Type a

Graphical network of the top 20 diseases related to Cockayne Syndrome, Type a:



Diseases related to Cockayne Syndrome, Type a

Symptoms & Phenotypes for Cockayne Syndrome, Type a

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Ears:
malformed ears
sensorineural hearing loss

Head And Neck- Eyes:
optic atrophy
nystagmus
strabismus
cataracts
pigmentary retinopathy
more
Abdomen- Liver:
hepatomegaly

Head And Neck- Head:
microcephaly
mandible prognathism

Genitourinary- External Genitalia Male:
micropenis
cryptorchidism

Skeletal- Spine:
kyphosis
vertebral body abnormalities

Growth- Other:
intrauterine growth retardation
severe postnatal growth deficiency
cachectic dwarfism

Skeletal- Pelvis:
hypoplastic iliac wings
small, squared off pelvis

Endocrine Features:
hypogonadism
irregular menstrual cycles

Laboratory- Abnormalities:
increased cellular sensitivity to uv light
thymic hormone decreased
at least 2 complementation groups
abnormal myelination in sural nerve biopsies
disturbed visual and brainstem auditory evoked responses indicative of cns demyelination

Head And Neck- Nose:
slender nose

Skeletal- Hands:
sclerotic ivory phalangeal epiphyses

Muscle Soft Tissue:
decreased subcutaneous adipose tissue

Neurologic- Central Nervous System:
mental retardation
cerebral atrophy
seizures
dementia
basal ganglia calcifications
more
Neurologic- Peripheral Nervous System:
ataxia
tremor
peripheral neuropathy
dysmyelination
weakness
more
Abdomen- Spleen:
splenomegaly

Genitourinary- Kidneys:
renal failure
proteinuria

Skin Nails & Hair- Skin:
anhidrosis
photosensitivity
dry skin
scarring
pigmentation
more
Head And Neck- Face:
loss of facial adipose tissue
wizened face

Head And Neck- Teeth:
malocclusion
delayed eruption of deciduous teeth
dental caries
absent/hypoplastic teeth

Cardiovascular- Vascular:
hypertension

Cardiovascular- Heart:
cardiac arrhythmias

Skeletal- Skull:
thickened calvarium

Skeletal- Limbs:
mild to moderate joint limitation

Skin Nails & Hair:
precociously senile appearance

Skin Nails & Hair- Hair:
thin, dry hair


Clinical features from OMIM:

216400

Human phenotypes related to Cockayne Syndrome, Type a:

32 (show top 50) (show all 66)
id Description HPO Frequency HPO Source Accession
1 optic atrophy 32 HP:0000648
2 nystagmus 32 HP:0000639
3 dysarthria 32 HP:0001260
4 ataxia 32 HP:0001251
5 tremor 32 HP:0001337
6 strabismus 32 HP:0000486
7 cerebral atrophy 32 HP:0002059
8 hepatomegaly 32 HP:0002240
9 splenomegaly 32 HP:0001744
10 seizures 32 HP:0001250
11 microcephaly 32 HP:0000252
12 pigmentary retinopathy 32 HP:0000580
13 proteinuria 32 HP:0000093
14 micropenis 32 HP:0000054
15 anhidrosis 32 HP:0000970
16 kyphosis 32 HP:0002808
17 sparse hair 32 HP:0008070
18 loss of facial adipose tissue 32 HP:0000292
19 intrauterine growth retardation 32 HP:0001511
20 muscle weakness 32 HP:0001324
21 renal insufficiency 32 HP:0000083
22 cryptorchidism 32 HP:0000028
23 intellectual disability 32 HP:0001249
24 cataract 32 HP:0000518
25 hypertension 32 HP:0000822
26 arrhythmia 32 HP:0011675
27 hypogonadism 32 HP:0000135
28 dry skin 32 HP:0000958
29 hypermetropia 32 HP:0000540
30 dementia 32 HP:0000726
31 dental malocclusion 32 HP:0000689
32 menstrual irregularities 32 HP:0000858
33 polyneuropathy 32 HP:0001271
34 decreased nerve conduction velocity 32 HP:0000762
35 increased cellular sensitivity to uv light 32 HP:0003224
36 basal ganglia calcification 32 HP:0002135
37 sensorineural hearing impairment 32 HP:0000407
38 dry hair 32 HP:0011359
39 gait disturbance 32 HP:0001288
40 delayed eruption of primary teeth 32 HP:0000680
41 decreased lacrimation 32 HP:0000633
42 slender nose 32 HP:0000417
43 normal pressure hydrocephalus 32 HP:0002343
44 patchy demyelination of subcortical white matter 32 HP:0002545
45 thymic hormone decreased 32 HP:0003357
46 hypoplastic iliac wing 32 HP:0002866
47 carious teeth 32 HP:0000670
48 abnormal auditory evoked potentials 32 HP:0006958
49 severe postnatal growth retardation 32 HP:0008850
50 cutaneous photosensitivity 32 HP:0000992

GenomeRNAi Phenotypes related to Cockayne Syndrome, Type a according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 8.62 ERCC6 ERCC8

MGI Mouse Phenotypes related to Cockayne Syndrome, Type a:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 hearing/vestibular/ear MP:0005377 8.62 ERCC6 ERCC8

Drugs & Therapeutics for Cockayne Syndrome, Type a

Search Clinical Trials , NIH Clinical Center for Cockayne Syndrome, Type a

Genetic Tests for Cockayne Syndrome, Type a

Genetic tests related to Cockayne Syndrome, Type a:

id Genetic test Affiliating Genes
1 Cockayne Syndrome Type a 29

Anatomical Context for Cockayne Syndrome, Type a

MalaCards organs/tissues related to Cockayne Syndrome, Type a:

39
Skin, Bone

Publications for Cockayne Syndrome, Type a

Articles related to Cockayne Syndrome, Type a:

id Title Authors Year
1
Prenatal diagnosis of Cockayne syndrome type A based on the identification of two novel mutations in the ERCC8 gene. ( 19309286 )
2009
2
Cockayne syndrome type A: novel mutations in eight typical patients. ( 16865293 )
2006
3
Characterisation of novel mutations in Cockayne syndrome type A and xeroderma pigmentosum group C subjects. ( 15744458 )
2005
4
CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism. ( 14661080 )
2004

Variations for Cockayne Syndrome, Type a

UniProtKB/Swiss-Prot genetic disease variations for Cockayne Syndrome, Type a:

71
id Symbol AA change Variation ID SNP ID
1 ERCC8 p.Ala160Val VAR_025380 rs121434325
2 ERCC8 p.Ala205Pro VAR_025381 rs121434326
3 ERCC8 p.Ala160Thr VAR_063507 rs281875222
4 ERCC8 p.Trp194Cys VAR_063508 rs281875223
5 ERCC8 p.Leu202Ser VAR_063509 rs281875224
6 ERCC8 p.Asp266Gly VAR_063510 rs281875225

ClinVar genetic disease variations for Cockayne Syndrome, Type a:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 ERCC8 NM_000082.3(ERCC8): c.37G> T (p.Glu13Ter) single nucleotide variant Pathogenic rs121434324 GRCh38 Chromosome 5, 60944972: 60944972
2 ERCC8 ERCC8, 279-BP DEL, 81-BP DEL deletion Pathogenic
3 ERCC8 NM_000082.3(ERCC8): c.966C> A (p.Tyr322Ter) single nucleotide variant Pathogenic rs121434323 GRCh37 Chromosome 5, 60186791: 60186791
4 ERCC8 NM_000082.3(ERCC8): c.479C> T (p.Ala160Val) single nucleotide variant Pathogenic/Likely pathogenic rs121434325 GRCh37 Chromosome 5, 60200621: 60200621
5 ERCC8 NM_000082.3(ERCC8): c.613G> C (p.Ala205Pro) single nucleotide variant Pathogenic rs121434326 GRCh37 Chromosome 5, 60198273: 60198273
6 ERCC8 NM_000082.3(ERCC8): c.141delC (p.Asn47Lysfs) deletion Pathogenic rs786205176 GRCh38 Chromosome 5, 60928896: 60928896
7 ERCC8 NM_000082.3(ERCC8): c.300C> G (p.Tyr100Ter) single nucleotide variant Likely pathogenic rs143367518 GRCh37 Chromosome 5, 60214191: 60214191
8 ERCC8 NM_000082.3(ERCC8): c.173+1119G> C single nucleotide variant Pathogenic rs1043679457 GRCh37 Chromosome 5, 60223572: 60223572

Expression for Cockayne Syndrome, Type a

Search GEO for disease gene expression data for Cockayne Syndrome, Type a.

Pathways for Cockayne Syndrome, Type a

GO Terms for Cockayne Syndrome, Type a

Biological processes related to Cockayne Syndrome, Type a according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 9.37 ERCC6 ERCC8
2 DNA repair GO:0006281 9.32 ERCC6 ERCC8
3 response to oxidative stress GO:0006979 9.26 ERCC6 ERCC8
4 transcription-coupled nucleotide-excision repair GO:0006283 9.16 ERCC6 ERCC8
5 response to UV GO:0009411 8.96 ERCC6 ERCC8
6 response to X-ray GO:0010165 8.62 ERCC6 ERCC8

Molecular functions related to Cockayne Syndrome, Type a according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 protein complex binding GO:0032403 9.16 ERCC6 ERCC8
2 DNA-dependent ATPase activity GO:0008094 8.96 ERCC6 ERCC8
3 DNA helicase activity GO:0003678 8.62 ERCC6 ERCC8

Sources for Cockayne Syndrome, Type a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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