Cockayne Syndrome

Excerpt

Cockayne syndrome is an autosomal recessive rare genetic disorder resulting from a DNA repair defect, leading to heightened sensitivity of cells in affected individuals to the lethal effects of UV light. Individuals with this disorder display unique facial characteristics, including sunken eyes, a beaked nose, and prominent ears, and also experience progressive dementia. In addition to these characteristics, individuals with Cockayne syndrome frequently exhibit cachectic dwarfism, intellectual disabilities, skin and hair thinning, failure to thrive, short stature with a stooped standing posture, microcephaly, progressive neurological dysfunction resulting from demyelination, retinal degeneration accompanied by pigmented retinopathy and optic atrophy, kyphoscoliosis, gait defects, neuromotor abnormalities, compromised vision and hearing, and sun sensitivity.

Cockayne syndrome was first identified in 1936 by the British physician Dr Edward Alfred Cockayne. Cockayne syndrome manifests as a spectrum that can be divided into 3 types—I, II, and III. This syndrome is specifically associated with mutations in 2 defective excision repair cross-complementation genes (ERCC)—the ERCC8 (Cockayne syndrome A or CSA) gene for Cockayne syndrome type I and the ERCC6 (Cockayne syndrome B or CSB) gene for Cockayne syndrome type II. Cockayne syndrome type II is the most severe variant that manifests at birth, and individuals typically succumb within the first decade of life. Cockayne syndrome type I becomes evident in early childhood, with death typically occurring in early adolescence. Cockayne syndrome type III represents a milder form that becomes apparent later in life. An additional variant—the xeroderma pigmentosum–Cockayne syndrome overlap complex—stems from mutations in different ERCC genes such as ERCC2, ERCC3, and XPD.

Unlike xeroderma pigmentosum, where sun sensitivity is associated with an elevated risk of skin cancer, individuals with Cockayne syndrome are sun-sensitive but do not exhibit an increased rate of cancer. The treatment for CS is mainly supportive and focuses on managing and preventing the associated complications. Children affected by Cockayne syndrome experience a reduced life expectancy, with the majority succumbing by early adolescence. Thus, early engagement of a multidisciplinary healthcare team is crucial in mitigating morbidity and enhancing the overall quality of life.