Cockayne Syndrome, Type A

Clinical Characteristics
Ocular Features: 

A progressive pigmentary retinopathy of a salt-and-pepper type and optic atrophy are commonly seen.  Retinal vessels are often narrowed and older patients can have typical bone spicule formation.  Night blindness, strabismus, and nystagmus may be present as well.  Enophthalmos, hyperopia, poor pupillary responses, and cataracts have been observed.  The lens opacities may in the nucleus or in the posterior subcapsular area and are often present in early childhood.  The ERG is often flat but may show some scotopic and photopic responses which are more marked in older individuals.  Vision loss is progressive but is better than expected in some patients based on the retina and optic nerve appearance.  The cornea may have evidence of exposure keratitis as many patients sleep with their eyes incompletely closed.  Recurrent corneal erosions have been reported in some patients.

The complete ocular phenotype and its natural history have been difficult to document due to the aggressive nature of this disease.

Ocular histopathology in a single patient (type unknown) revealed widespread pigment dispersion, degeneration of all retinal layers as well as thinning of the choriocapillaris and gliosis of the optic nerve.  Excessive lipofuscin deposition in the RPE was seen.

Systemic Features: 

Slow somatic growth and neural development are usually noted in the first few years of life.  Young children may acquire some independence and motor skills but progressive neurologic deterioration is relentless with loss of milestones and eventual development of mental retardation or dementia.  Patients often appear small and cachectic, with a 'progeroid' appearance.  The hair is thin and dry, and the skin is UV-sensitive but the risk of skin cancer is not increased.  Sensorineural hearing loss and dental caries are common.  Skeletal features include microcephaly, kyphosis, flexion contractures of the joints, large hands and feet, and disproportionately long arms and legs.  Perivascular calcium deposits are often seen, particularly in various brain structures while the brain is small with diffuse atrophy and patchy demyelination of white matter.  Peripheral neuropathy is characterized by slow conduction velocities.  Poor thermal regulation is often a feature. 

Type A is considered the classic form of CS.  Neurological deterioration and atherosclerotic disease usually lead to death early in the 2nd decade of life but some patients have lived into their 20s.  


There is a great deal of clinical heterogeneity in Cockayne syndrome.  Type A results from homozygous or heterozygous mutations in ERCC8 (5q12).  CS type B (133540), is caused by mutations in ERCC6, and has an earlier onset with more rapidly progressive disease.  Both mutations impact excision-repair cross-complementing proteins important for DNA repair during replication.

Type III (216411) is poorly defined but seems to have a considerably later onset and milder disease.  The mutation in type III is unknown. 

Some patients have combined phenotypical features of Cockayne syndrome (CS) and xeroderma pigmentosum (XP) known as the XP-CS complex (216400).  Defective DNA repair resulting from mutations in nucleotide excision-repair cross-complementing or ERCC genes is common to both disorders.  Two complementation groups have been identified in CS and seven in XP.  XP patients with CS features fall into only three (B, D, G) of the XP groups.  XP-CS patients have extreme skin photosensitivity and a huge increase in skin cancers of all types.  They also have an increase in nervous system neoplasms. 

There may be considerable overlap in clinical features and rate of disease progression among all types.

Autosomal recessive
Treatment Options: 

No specific treatment is available for Cockayne syndrome.  Supportive care for specific health problems, such as physical therapy for joint contractures, is important. 

Justification of cataract extraction should be made on a case by case basis.  Lagophthalmos requires that corneal lubrication be meticulously maintained.

Article Title: 

The Cockayne Syndrome Natural History (CoSyNH) study: clinical findings in 102 individuals and recommendations for care

Wilson BT, Stark Z, Sutton RE, Danda S, Ekbote AV, Elsayed SM, Gibson L, Goodship JA, Jackson AP, Keng WT, King MD, McCann E, Motojima T, Murray JE, Omata T, Pilz D, Pope K, Sugita K, White SM, Wilson IJ. The Cockayne Syndrome Natural History (CoSyNH) study: clinical findings in 102 individuals and recommendations for care. Genet Med. 2015 Jul 23. doi: 10.1038/gim.2015.110. [Epub ahead of print].

PubMed ID: 

Ocular findings in Cockayne syndrome

Traboulsi EI, De Becker I, Maumenee IH. Ocular findings in Cockayne syndrome. Am J Ophthalmol. 1992 Nov 15;114(5):579-83.

PubMed ID: 

Cockayne syndrome and xeroderma pigmentosum

Rapin I, Lindenbaum Y, Dickson DW, Kraemer KH, Robbins JH. Cockayne syndrome and xeroderma pigmentosum. Neurology. 2000 Nov 28;55(10):1442-9. Review. PubMed PMID:

PubMed ID: 
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