Cockaynesyndrom

Cockayne syndrome is a rare autosomal recessive disorder caused by mutations in genes involved in transcription-coupled nucleotide excision repair, most often ERCC6 (CSB) or ERCC8 (CSA). Defects in this repair pathway lead to improper handling of DNA damage in actively transcribed genes, resulting in sensitivity to ultraviolet light and a progressive neurodevelopmental and multisystem degenerative process.

Clinical features typically appear in infancy or early childhood and include growth failure with microcephaly, photosensitivity with sun-induced skin changes, and developmental delay followed by progressive neurologic deterioration (hypotonia, ataxia, dysarthria). Patients often have sensorineural hearing loss, vision problems, skeletal and dental anomalies, and a distinctive facial appearance. The course is highly variable but generally progressive, with worsening neurologic function and reduced lifespan.

Genetic testing identifies biallelic mutations in ERCC6 or ERCC8. The disorder is inherited in an autosomal recessive manner.

There are three main clinical subtypes: Type I (classic severe form with onset in infancy and growth failure), Type II (congenital onset with more severe growth failure and limited postnatal development), and Type III (milder form with later onset and slower progression).

Brain imaging may show cerebral atrophy and white matter changes; assessments reflect multisystem involvement. Management is supportive and multidisciplinary, focusing on photoprotection, nutrition, physical, occupational, and speech therapy, vision and hearing support, and treatment of complications. There is no cure, and prognosis depends on subtype, with most individuals experiencing significant neurodevelopmental impairment and shortened lifespan.