New genetic clues explain severe eye damage in patients with rare XP disorder

HYDERABAD: In a significant breakthrough for rare disease research in India, doctors at the LV Prasad Eye Institute (LVPEI) have uncovered new genetic causes behind severe eye damage in patients with xeroderma pigmentosum (XP), a rare inherited condition that makes individuals extremely vulnerable to sunlight.The findings, published in the journal ‘Cornea,' are the first-of-their kind in the Indian population. Researchers studied 23 XP patients—most of them children and young adults—shedding new light on how the disorder affects the eyes, an aspect often overshadowed by its well-known skin complications. XP has no cure and occurs due to a defect in the body's ability to repair DNA damaged by ultraviolet rays, meaning even minimal exposure to sunlight can result in serious skin and eye injury. Abnormal growthAlarmingly, more than one-third of the patients developed abnormal growths on the eye surface, some of which have the potential to turn cancerous. Dr Sunita Chaurasia, the study's lead author, said that while XP is commonly associated with skin damage, its eye-related complications are frequently overlooked in the early stages. "By the time eye problems are detected, the damage is usually severe and can lead to blindness. This is why there is a need for early diagnosis, genetic counselling, sun protection, and regular eye check-ups to protect vision before damage becomes irreversible," she added. The study revealed that all patients suffered from severe photophobia, or extreme sensitivity to light, along with varying degrees of vision impairment. Nearly all showed damage to the outer surface of the eye, while 80% had corneal involvement and about 70% exhibited abnormalities of the eyelids, underscoring the widespread and debilitating impact of the condition on ocular health. Major risk factorA striking observation was that most patients were born to parents who were closely related, highlighting consanguineous marriages as a major risk factor in the occurrence of the disease. Through advanced genetic testing, researchers identified 15 disease-causing variants of the XP-C gene, 12 of which had never been reported before. In another first for India, XP-E gene variants were also detected. Patients carrying the XP-E variant were found to have a higher risk of developing severe eye disease.