Ocular Manifestations and Genetic Spectrum of Xeroderma Pigmentosum: Insights From an Indian Cohort in a Global...

Xeroderma Pigmentosum (XP) is a rare autosomal recessive disorder caused by defective nucleotide excision repair. Although dermatological features are well characterized, data on ocular manifestations and associated genotypes in Indian populations remain limited. This study aimed to delineate the ocular phenotype and underlying genetic variants in Indian patients with XP and compare them with global data.

Retrospective review of 23 patients with genetically confirmed XP was conducted. Variant pathogenicity was assessed using in silico tools. Logistic regression analysis and Generalized Estimating Equations model with a logit link function was used to evaluate any potential associations between clinical genetic parameters with the occurrence of ocular surface neoplasia (OSN).

The cohort (median age: 24 years; male: female = 15:8) had a high consanguinity rate (69.6%). All patients reported of photophobia and visual impairment. Ocular surface dryness was also a notable complaint in 17%. Frequent ocular findings included conjunctival abnormalities (97%), corneal involvement (80%), and eyelid changes (70%). OSN or lid/adnexal tumors together were observed in 37% of eyes. Whole exome sequencing identified 18 pathogenic/likely pathogenic variants-15 in XP-C and 3 in DDB2 (XP-E), including 12 novel variants. There was a statistically significant increased risk of OSN in XP-E subtype compared with XP-C subtype.

XP-C was the predominant subtype, followed by XP-E in patients with XP with ocular involvement. XP-E subtype has been reported for the first time in Indian data in this study. Most variants were frameshift or stop gain. The patients with XP-E subtype may be more at risk of OSN development. These findings underscore the importance of routine ocular surveillance and genetic testing in XP.