Cockayne syndrome

Tarakad S Ramachandran MD (Dr. Ramachandran of SUNY Upstate Medical University has no relevant financial relationships to disclose.)
AHM M Huq MD PhD, editor. (Dr. Huq of Wayne State University has no relevant financial relationships to disclose.)
Originally released April 7, 1995; last updated August 4, 2016; expires August 4, 2019

This article includes discussion of Cockayne syndrome, CKN1, CKN2, Cockayne-Neill-Dingwall syndrome, and progeroid nanism. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

The features of Cockayne syndrome include dwarfism, cataracts, optic atrophy, mental retardation, an unusual facies and body habitus, hearing loss, a peculiar form of fine pigmentary retinitis without the typical spicules seen in retinitis pigmentosa, and some similarities to the condition progeria. This condition can be caused by 2 gene mutations, CNK1 (ERCC8) and ERCC6, located on the 5 and 10 chromosomes respectively, causing 2 variations: Cockayne syndrome type A, secondary to an ERCC8 mutation, and Cockayne syndrome type B with ERCC6 mutation. The latter causes hypersensitivity to ultraviolet light, secondary to a DNA repair defect. The syndrome is also associated with mutations of the XPB, XPD, and XPG genes. Cockayne syndrome is extremely rare, with approximately 200 cases in the literature. Death generally occurs by the age of 30 years, secondary to inanition or infection. Management focuses on symptomatic therapy.

Key points

 

• Cockayne syndrome is an autosomal recessive multisystem disorder, predominantly characterized by neurologic and sensory impairment, cachectic dwarfism, and photosensitivity.

 

• Although the most typical form is known as Cockayne syndrome type I, a severe form seen at birth is known as Cockayne syndrome type II (known as cerebro-oculo-facial-skeletal syndrome or Pena-Shokeir syndrome type II). A much milder form is known as Cockayne syndrome type III. In addition, there is also an entity known as xeroderma pigmentosum-Cockayne syndrome.

 

• Diagnosis is made on clinical grounds and, when needed, molecular genetic testing.

 

• Treatment consists of purely supportive care.

 

• Molecular prenatal diagnosis of Cockayne syndrome type A has been successful. Carrier detection (50% chance of being an asymptomatic carrier) is available once the mutations have been identified in the proband.

 

• Cockayne syndrome is characterized by a deficiency in the transcription-couple DNA repair pathway caused by mutations mainly in the Cockayne syndrome group B gene (ERCC6).

Historical note and terminology

Cockayne syndrome, or Cockayne-Neill-Dingwall syndrome, was first reported by Cockayne in 1936 in a brother and sister with dwarfism and retinal atrophy (Cockayne 1936). He made a follow-up report in 1946, at which time he reported that the children were markedly different than at first presentation (Cockayne 1946). The features of the condition included the postnatal onset of dwarfism, cataracts, optic atrophy, mental retardation, an unusual facies and body habitus, hearing loss, and a peculiar form of fine pigmentary retinitis without the typical spicules seen in retinitis pigmentosa. Neill and Dingwall later reported on another child and commented on some similarities to the condition progeria (Neill and Dingwall 1950). Macdonald and colleagues reported 3 further patients in a family (Macdonald et al 1960). They saw a clear and sharp distinction between Cockayne syndrome and progeria, a point that has been clearly borne out by the discovery of the underlying pathogenesis in Cockayne syndrome.

Cockayne syndrome can be caused by 2 gene mutations, CNK1 (ERCC8) and ERCC6, located on the 5 and 10 chromosomes respectively, causing 2 variations: Cockayne syndrome type A, secondary to an ERCC8 mutation, and Cockayne syndrome type B with ERCC6 mutation. The latter causes hypersensitivity to ultraviolet light, secondary to a DNA repair defect. The syndrome is also associated with mutations of the XPB, XPD, and XPG genes.

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