Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight (photosensitivity), eye disorders and premature aging. Failure to thrive and neurological disorders are criteria for diagnosis, while photosensitivity, hearing loss, eye abnormalities, and cavities are other very common features. Problems with any or all of the internal organs are possible. It is associated with a group of disorders called leukodystrophies, which are conditions characterized by degradation of neurological white matter. The underlying disorder is a defect in a DNA repair mechanism. Unlike other defects of DNA repair, patients with CS are not predisposed to cancer or infection. Cockayne syndrome is a rare but destructive disease usually resulting in death within the first or second decade of life. The mutation of specific genes in Cockayne syndrome is known, but the widespread effects and its relationship with DNA repair is yet to be well understood.It is named after English physician Edward Alfred Cockayne (1880–1956) who first described it in 1936 and re-described in 1946. Neill-Dingwall syndrome was named after Mary M. Dingwall and Catherine A. Neill. These two scientists described the case of two brothers with Cockayne syndrome and asserted it was the same disease described by Cockayne. In their article, the two contributed to the signs of the disease through their discovery of calcifications in the brain.
The normal function of the TREX1 gene is to provide instructions for making the 3-prime repair exonuclease 1 enzyme. This enzyme is a DNA exonuclease, which means it trims molecules of DNA by removing DNA building blocks (nucleotides) from the ends of the molecules. In this way, it breaks down unneeded DNA molecules or fragments that may be generated during genetic material in preparation for cell division, DNA repair, cell death, and other processes. Changes (mutations) to the TREX1 gene can result in a range of conditions, one of which is RVCL. The mutant TREX1 protein is produced and mislocalized. Haploinsufficiency of TREX1 does not explain the disease, since the parents of patients with Aicairdi-Goutieres syndrome, a disease characterized by insufficient TREX1 activity, are completely healthy with only one functional TREX1 allele. Different mutations in the TREX1 gene have also been identified in people with disorders involving the immune system. These disorders include a chronic inflammatory disease called Aicardi-Goutieres syndrome, as well as systemic lupus erythematosus (SLE), including a rare form of SLE called chilblain lupus that mainly affects the skin. Those diseases, which are inflammatory, may have a completely distinct mechanism compared with that of RVCL. The TREX1 gene is located on chromosome 3: base pairs 48,465,519 to 48,467,644

Pathogenesis
The main pathologic process centers on small blood vessels that prematurely "drop out" and disappear. The retina of the eye and white matter of the brain appear to be among the most sensitive to this pathologic process.