PD09 Life expectancy of patients with xeroderma pigmentosum: evidence from a UK study

Abstract Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of DNA repair, characterized by extreme sensitivity to ultraviolet radiation. Patients are at risk of skin cancers and ocular surface disease, and approximately one-third of patients experience progressive neurodegeneration. Life expectancy varies significantly based on complementation group, disease severity and access to preventive measures. Obtaining reliable survival estimates for this rare and genetically heterogeneous disease can be challenging, leading to variability in reported survival rates. A National Institutes of Health study of 106 patients (1971–2009) reported a median age at death of 29 years for patients with XP with neurodegeneration, and 37 years for those without. These statistics are frequently cited in academic literature and widely reported on publicly accessible websites. Our aim was to assess the life expectancy of patients with XP receiving multidisciplinary care at the UK National XP Service and assess patients’ and families’ understanding of their prognosis. We conducted a longitudinal study of 89 patients seen annually in the UK National XP Service from 2015 to 2024. Mortality events were documented and categorized between those with and without neurodegeneration. To evaluate patient perceptions on life expectancy, 24 clinic attendees completed a short survey between February and July 2023. Over a 9-year period, 15 deaths (17%) were recorded, comprising 11 cases with neurodegeneration (groups A, B, D, F and G) and four cases without (groups A, C and V). There were no deaths attributable to skin cancer. Four deaths were linked to internal malignancies. The median survival age was calculated as 50 years (95% confidence interval 34 to not calculable) for those with neurological involvement, and 81 years (95% confidence interval 81 to not calculable) for those without. The latter is comparable with the general UK population (78.6 years for men, 82.6 years for women; 2020–2022 data). Only 11 of 24 survey respondents (46%) believed that life expectancy in neurologically unaffected patients with XP was normal. One respondent (4%) estimated life expectancy at 20–29 years, eight (31%) at 30–39 years and one (4%) at 50–59 years, and three reported uncertainty. We present evidence of improved survival outcomes in patients with XP in the UK, both with and without neurological involvement. While life expectancy can be limited, particularly in the presence of neurodegeneration, advances in medical management and strict adherence to preventive measures have improved outcomes. It is important that outdated and potentially harmful information online is updated. Discussions with patients and families should convey that regular medical follow-ups, diligent photoprotection and timely intervention for skin cancers can enhance longevity and quality of life for those affected by XP.