xeroderma pigmentosum-Cockayne syndrome complex

Xeroderma pigmentosum-Cockayne syndrome complex is a very rare multisystem condition that combines the photosensitive skin abnormalities of xeroderma pigmentosum with the systemic and neurological features of Cockayne syndrome. Genetic alterations in one of the DNA repair genes — ERCC5, ERCC3, ERCC4, or ERCC2 — are responsible for the disorder. The condition typically presents in childhood with a range of features affecting the skin, eyes, and nervous system, including cognitive impairments and developmental challenges. It is extremely rare, affecting fewer than 1 in 1,000,000 people.

The clinical presentation of xeroderma pigmentosum-Cockayne syndrome complex is multisystem and variable. Neurologically, affected individuals often experience intellectual disability, global developmental delay, ataxia, spasticity, microcephaly, and sometimes confusion, hearing impairment, retinopathy, nystagmus, and optic atrophy. Cutaneous features include dry skin, skin rash, marked photosensitivity, urticaria, and poikiloderma, along with numerous pigmented freckles, dermal atrophy, and a prematurely aged appearance. Additional systemic manifestations may include short stature, cachexia, arteriosclerosis, hydrocephalus, and abnormalities of amino acid metabolism. Not all individuals experience all features, and severity varies considerably.

Xeroderma pigmentosum-Cockayne syndrome complex results from pathogenic variants in one of several genes that are crucial for DNA repair, specifically ERCC5, ERCC3, ERCC4, and ERCC2. These genetic alterations impair the ability to repair ultraviolet-induced DNA damage, leading to the characteristic skin findings as well as the systemic and neurological abnormalities. The inheritance pattern of this condition is not clearly defined, and families are encouraged to seek genetic counseling to better understand the implications for family planning and recurrence risks.

Currently, management focuses on supportive care and symptom management, as there are no treatments specifically approved for xeroderma pigmentosum-Cockayne syndrome complex. A multidisciplinary approach is central to care, with regular surveillance to detect emerging complications before they become serious. Management is tailored to the individual, and patients should discuss treatment options with their healthcare team. Genetic counseling is also recommended to support families in understanding the condition and planning for the future.

Outcomes for xeroderma pigmentosum-Cockayne syndrome complex vary widely between individuals, and severity and symptoms vary widely between individuals. The condition may progress, stabilize, or follow a variable course, with some individuals experiencing periods of relative stability following initial complications. With current standards of care, many individuals benefit from improved management of symptoms, and outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition, including genetic counselors, to navigate ongoing management and support.