A complex inherited and congenital disorder
characterized by the association of dwarfism, deafness, microcephaly, facial
anomalies, ataxia, photosensitivity, retinal atrophy, and renal
insufficiency with premature aging and atherosclerosis.
Deafness-Dwarfism-Retinal Atrophy; Dwarfism with Renal
Atrophy and Deafness; Neill-Dingwall Syndrome; Progeroid Nanism.
First described by the English Physician Edward Alfred
Cockayne in 1936.
Occurs in approximately 1:200,000 live births. No ethnic
or sexual predilection has been reported.
Autosomal recessive. Cockayne syndrome (CS)
type I (also called type A, see Clinical Aspects) results from a defect in the
CS type A or CSA or ERCC8 (excision repair cross-complementing rodent repair
deficiency, complementation group 8) gene, which is located on chromosome 5.
Cells carrying the mutated ERCC8 gene exhibit a hypersensitivity to
ultraviolet light. After exposure to ultraviolet light, these cells fail to
recover their ability to synthesize ribonucleic acid and to repair or excise
and degrade lesions in deoxyribonucleic acid strands. In CS type II (type
B), the mutation affects the transcription-coupled and global genome DNA
excision repair gene ERCC6 (excision repair cross-complementing rodent repair
deficiency, complementation group 6), which has been mapped to 10q11.
A defective transcription-coupled repair of
oxidative damages to the DNA contributes to developmental defects.
In classic CS type I, the diagnosis is based on the
clinical findings, whereas the “nonclassic” form is confirmed by DNA
repair assays in lymphoblasts or skin fibroblasts. In older children,
classic CS type I should be suspected in the presence of both major and
three minor criteria. In infants or toddlers, the diagnosis is likely when
one minor and both major criteria are fulfilled and abnormalities in DNA
repair are present. The major criteria consist of (1) postnatal growth
retardation (height and weight below the fifth percentile at 2 years of age
resulting in “cachectic dwarfism” appearance) and (2) progressive
neurologic dysfunction (early developmental delay and progressive
deterioration). Intracranial pericapillary calcifications (in cortex and
basal ganglia), leukodystrophy with scattered neuronal loss, and normal
pressure hydrocephalus may be present. The seven minor criteria are (1)
dermal photosensitivity (poikiloderma), (2) pigmentary retinopathy,
blindness, and/or cataracts, (3) diffuse and segmental peripheral
demyelination with decreased nerve conduction velocity, (4) sensorineural
hearing loss, (5) sclerotic epiphyses, vertebral and pelvic abnormalities,
thickening of the calvarium, (6) thin skin and brittle hair, sunken eyes, and
stooped standing posture, and (7) dental cavities. In CS type II, the
diagnosis is based on the findings of failure to thrive beginning right from
birth with severely delayed gains in height and weight combined with
absent or minimal progress in the neurologic development. Eye
anomalies are frequent and include congenital cataracts and other structural
ocular defects such as microphthalmos and microcornea.
Premature aging is the hallmark of all types of
CS. CS I (type A or “classic” form) presents in infancy and is less severe
than CS ...