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  • Updated 09.05.2020
  • Released 04.07.1995
  • Expires For CME 09.05.2023

Cockayne syndrome

Introduction

Overview

The features of Cockayne syndrome include dwarfism, cataracts, optic atrophy, intellectual disability, 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 two gene mutations, CNK1 (ERCC8 or CSA) and ERCC6 (CSB), located on the 5 and 10 chromosomes respectively, causing two 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. Current management focuses on symptomatic therapy, although the possibility of gene therapy is under investigation.

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, an entity known as xeroderma pigmentosum-Cockayne syndrome is recognized.

• 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 or CSB).

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 (14). He made a follow-up report in 1946, at which time he reported that the children were markedly different than at first presentation (15). 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 (61). Macdonald and colleagues reported three additional patients in a family (51). 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 two gene mutations, CNK1 (ERCC8 or CSA) and ERCC6, located on the 5 and 10 chromosomes respectively, causing two variations: Cockayne syndrome type A, secondary to an ERCC8 mutation, and Cockayne syndrome type B with ERCC6 (or CSB) 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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