Clinical characteristics: Cockayne syndrome (referred to as CS in this GeneReview) spans a continuous phenotypic spectrum that includes:
CS type I, the "classic" or "moderate" form;
CS type II, a more severe form with symptoms present at birth; this form overlaps with cerebrooculofacioskeletal (COFS) syndrome;
CS type III, a milder and later-onset form;
COFS syndrome, a fetal form of CS.
CS type I is characterized by normal prenatal growth with the onset of growth and developmental abnormalities in the first two years. By the time the disease has become fully manifest, height, weight, and head circumference are far below the fifth percentile. Progressive impairment of vision, hearing, and central and peripheral nervous system function leads to severe disability; death typically occurs in the first or second decade.
CS type II is characterized by growth failure at birth, with little or no postnatal neurologic development. Congenital cataracts or other structural anomalies of the eye may be present. Affected children have early postnatal contractures of the spine (kyphosis, scoliosis) and joints. Death usually occurs by age five years.
CS type III is a phenotype in which major clinical features associated with CS only become apparent after age two years; growth and/or cognition exceeds the expectations for CS type I.
COFS syndrome is characterized by very severe prenatal developmental anomalies (arthrogryposis and microphthalmia).
Diagnosis/testing: The diagnosis of Cockayne syndrome is established in a proband with the identification of biallelic pathogenic variants in ERCC6 or ERCC8 on molecular genetic testing.
Management: Treatment of manifestations: Feeding gastrostomy tube placement as needed; individualized educational programs for developmental delay; medications for tremor and spasticity as needed; physical therapy to prevent contractures; use of sunglasses for lens/retina protection; treatment of cataracts, and other ophthalmologic complications, hearing loss, hypertension, and gastroesophageal reflux as in the general population. Aggressive dental care to minimize dental caries; use of sunscreens and limitation of sun exposure for cutaneous photosensitivity.
Surveillance: Biannual assessment of diet, nervous system, and ophthalmologic status. Yearly assessment for complications such as hearing loss, hepatic or renal dysfunction, and hypertension.
Agents/circumstances to avoid: Excessive sun exposure and use of metronidazole. Extra vigilance is needed for opioid and sedative use. Use of growth hormone treatment is not recommended in those with CS.
Genetic counseling: Cockayne syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible if the ERCC6 or ERCC8 pathogenic variants in the family are known.
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