Cockayne syndrome: Review of 140 cases

Abstract

To define diagnostic criteria for Cockayne Syndrome (CS) and to identify in detail the complications of the condition, a comprehensive review of 140 cases of CS was performed. Criteria required for the diagnosis include poor growth and neurologic abnormality; other very common manifestations include sensorineural hearing loss, cataracts, pigmentary retinopathy, cutaneous photosensitivity, and dental caries. The mean age of death in reported cases is 12 3/12 years, though a few affected individuals have lived into their late teens and twenties. Prenatal growth failure, congenital structural eye anomalies, severe neurologic dysfunction from birth, and the presence of cataracts within the first 3 years of life are predictors of severe disease and early death. In contrast with other disorders of chromosome or DNA repair, cancer has never been reported in a classical CS patient, and there appears to be no predisposition to infectious complications. The wide spectrum of symptoms and severity of the disease suggest that biochemical and genetic heterogeneity exist. CS is an uncommon but devastating genetic condition which will be better understood as the biochemical interrelationships between DNA replication and repair, and between growth, homeostasis, and oncogenesis are unraveled.

Effect of mutations in XPD(ERCC2) on pregnancy and prenatal development in mothers of patients with trichothiodystrophy or xeroderma pigmentosum

“…COFS is closely related to Cockayne syndrome (CS) type II and both may be associated with low birth weight. [25][26][27] COFS can be caused by mutations in several nucleotide excision repair genes: CSB(ERCC6), XPG(ERCC5), or ERCC1 in addition to XPD. 25 However, a comprehensive literature review of 140 CS cases did not report severe pregnancy complications in any of the forms of CS.…”

“…25 However, a comprehensive literature review of 140 CS cases did not report severe pregnancy complications in any of the forms of CS. 27 Because most TTD and XP patients are compound heterozygotes, it is difficult to ascribe a clinical phenotype to a single mutation. As TTD is an autosomal recessive disorder, the mothers of the XPDaffected patients are obligate heterozygotes.…”

The role of Cockayne Syndrome group B (CSB) protein in base excision repair and aging

“…disrupted in the CSB gene (also called ERCC6) have increased susceptibility to skin cancer (van der Horst et al, 1997). The life expectancy of patients with CS is approximately 12 years (for extensive reviews on clinical characteristics of CS see (Nance and Berry, 1992) and (Licht et al, 2003). Several of the traits are reminiscent of normal aging, and CS has therefore been classified as a segmental premature aging syndrome.…”

Review of cases presenting with microcephaly and bilateral congenital cataract in a paediatric cataract clinic

“…This is followed by progressive mental and physical retardation, a prematurely aged appearance, microcephaly, ataxia, and sensorineural deafness. 5 Many have cutaneous photosensitivity and a history of redness or skin peeling following sun exposure should be sought. Progressive neurological deterioration leads to death by the second to third decade of life.…”