Cockayne syndrome: Year of the Zebra 2026

Cockayne syndrome, or CS, is a rare genetic neurodegenerative condition resulting from defects in DNA repair and is characterized by distinct facial characteristics, disrupted growth, developmental delays, sunlight sensitivity, and premature aging.

CS is caused by mutations, or pathogenic variants, in either the ERCC8 or ERCC6 gene, which code for the CSA and CSB proteins, respectively. This is an autosomal recessive condition, meaning that to be affected, a child must inherit two faulty copies of the gene, one from each parent. The CSA and CSB proteins from these genes are involved in the identification and repair of damaged DNA, the genetic code found in each cell.

Everyone’s DNA is routinely damaged by normal wear and tear in the human body over time, as well as by harmful radiation found in the environment such as UV rays; x-rays; and gamma rays. Usually, damaged DNA is repaired during a process called nucleotide excision repair, or NER. In CS, faulty ERCC8 or CRCC6 genes produce proteins that cannot identify or remove damaged DNA. The damaged DNA then builds-up and leads to cell dysfunction or cell death.

CSA and CSB proteins also do other jobs in cells, including the regulation of other proteins. Whether the symptoms found in individuals with CS are due to the loss of DNA repair functionality, these other jobs, or both is the subject of ongoing research.

Although CS affects overall growth and development, individuals with CS are happy and outgoing! They are very social and love to be around people!

CS affects the eyes, ears, muscles, gastrointestinal system, and skin, and may reduce the ability to fight infection. Affected individuals develop distinct facial features, such as sunken eyes, a slender nose, and prominent ears. Physical growth is disrupted resulting in microcephaly, or a small head, and short stature. Neurologic symptoms include intellectual disabilities, tremors, speech difficulties, dementia, and sometimes seizures. Hearing loss and eye problems, such as cataracts; and nystagmus, eye shaking or involuntary horizontal eye movement, are common. Patients may experience limited mobility due to muscle spasms or difficulty with walking. Individuals living with CS have swallowing and digestive problems and commonly are underweight. Even minimal exposure to sunlight can cause severe sunburns and in some it can cause redness and scaling skin around the eyes. Unlike related conditions, people with CS are not prone to getting skin cancer.

CS is suspected when a child has the characteristic facial features, developmental delay, sun sensitivity, and disrupted growth. MRI of the brain may show structural differences.

Definitive diagnosis of CS is made when genetic testing finds two pathogenic variants in either the ERCC8 or ERCC6 genes.

CS is typically categorized into three main types, distinguished by the age of onset and severity of symptoms.

Type I is the classic form. Symptoms appear within the first two years of life.

Type II is the most severe. Symptoms are present at birth or within the first few months.