Cockayne syndrome

Cockayne syndrome (CS), also known as Neill-Dingwall syndrome, is a rare autosomal recessive multisystem disorder characterized by growth failure, progressive neurological dysfunction, photosensitivity, and a distinctive facial appearance often described as 'cachectic dwarfism.' It belongs to a group of nucleotide excision repair (NER) disorders caused by pathogenic variants in the ERCC8 (CSA) gene or the ERCC6 (CSB) gene, which play critical roles in transcription-coupled nucleotide excision repair of DNA damage. The condition is classified into three subtypes based on severity and age of onset: CS type I (classical or moderate form), CS type II (severe or early-onset form, also called cerebro-oculo-facio-skeletal syndrome in its most severe presentation), and CS type III (a milder, later-onset form). The disease affects multiple body systems. Neurological features include progressive microcephaly, intellectual disability, cerebellar ataxia, spasticity, peripheral neuropathy, and sensorineural hearing loss. Brain imaging typically reveals leukodystrophy, cerebellar atrophy, and intracranial calcifications, particularly in the basal ganglia. Ophthalmological manifestations include cataracts, pigmentary retinopathy, and enophthalmos (sunken eyes). Affected individuals exhibit severe postnatal growth failure with short stature and low weight, a characteristic facial appearance with prominent ears and a thin nose, cutaneous photosensitivity, dental caries, and progressive joint contractures. Skeletal abnormalities and renal dysfunction may also occur. Lifespan is significantly reduced, with individuals with CS type I typically surviving into the second or third decade, while those with CS type II often die in early childhood. There is currently no cure or disease-modifying treatment for Cockayne syndrome. Management is supportive and multidisciplinary, focusing on symptom management and quality of life. This includes sun protection to minimize photosensitivity, physical and occupational therapy for motor difficulties, hearing aids or cochlear implants for hearing loss, nutritional support (including gastrostomy feeding when necessary), ophthalmological monitoring and cataract surgery when indicated, and regular dental care. Surveillance for renal and hepatic complications is also recommended. Genetic counseling is important for affected families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Cockayne syndrome