Cockayne syndrome is a rare disorder characterized by an abnormally small head size (microcephaly), a failure to gain weight and grow at the expected rate (failure to thrive) leading to very short stature, and delayed development.
The signs and symptoms of this condition are usually apparent from infancy, and they worsen over time. Most affected individuals have an increased sensitivity to sunlight (photosensitivity), and in some cases even a small amount of sun exposure can cause a sunburn or blistering of the skin. Other signs and symptoms often include hearing loss, vision loss, severe tooth decay, bone abnormalities, hands and feet that are cold all the time, and changes in the brain that can be seen on brain scans.
People with Cockayne syndrome have a serious reaction to an antibiotic medication called metronidazole. If affected individuals take this medication, it can cause life-threatening liver failure.
Cockayne syndrome is sometimes divided into types I, II, and III based on the severity and age of onset of symptoms. However, the differences between the types are not always clear-cut, and some researchers believe the signs and symptoms reflect a spectrum instead of distinct types. Cockayne syndrome type II is also known as cerebro-oculo-facio-skeletal (COFS) syndrome, and while some researchers consider it to be a separate but similar condition, others classify it as part of the Cockayne syndrome disease spectrum.
Cockayne syndrome is estimated to occur in 2 to 3 per million newborns in the United States and Europe.
Cockayne syndrome can result from mutations in either the ERCC6 gene (also known as CSB) or the ERCC8 gene (also known as CSA). These genes provide instructions for making proteins that are involved in repairing damaged DNA. DNA can be damaged by ultraviolet (UV) rays from the sun and by toxic chemicals, radiation, and unstable molecules called free radicals. Cells are usually able to fix DNA damage before it causes problems. However, in people with Cockayne syndrome, DNA damage is not repaired normally. As errors build up in DNA, cells malfunction and eventually die. The faulty DNA repair underlies photosensitivity in affected individuals, and researchers suspect that it also contributes to the other features of Cockayne syndrome. It is unclear how ERCC6 or ERCC8 gene mutations cause all of the varied features of this condition.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.