Xeroderma pigmentosum

Xeroderma pigmentosum (XP) is a rare inherited disorder characterized by extreme sensitivity to ultraviolet (UV) radiation from sunlight. It is caused by defects in the nucleotide excision repair (NER) pathway, which is responsible for repairing UV-induced DNA damage. There are eight complementation groups (XPA through XPG, and XP variant), each corresponding to mutations in different genes involved in DNA repair. The condition is also known by its abbreviation XP and has historically been referred to as 'moon children disease' due to the need for affected individuals to avoid sunlight. XP primarily affects the skin, eyes, and in some cases the nervous system. The earliest signs typically appear in infancy or early childhood and include severe sunburn after minimal sun exposure, freckling in sun-exposed areas before age two, and progressive skin changes including dryness (xerosis), abnormal pigmentation, and skin thinning. Affected individuals have a dramatically increased risk — estimated at more than 1,000-fold — of developing skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma, often before age 10. Ocular manifestations include photophobia, keratitis, corneal opacification, and eyelid tumors. Approximately 20–30% of patients develop progressive neurological degeneration, which may include sensorineural hearing loss, cognitive decline, diminished reflexes, and microcephaly, particularly in complementation groups XPA, XPB, XPD, and XPG. There is currently no cure for xeroderma pigmentosum. Management focuses on rigorous UV protection, including avoidance of sunlight, use of protective clothing, UV-filtering eyewear, and high-SPF sunscreen. Regular dermatological surveillance with early detection and removal of premalignant and malignant skin lesions is essential. Ophthalmological monitoring is also critical. Topical treatments such as 5-fluorouracil or imiquimod may be used for precancerous lesions. Oral retinoids have been used in some patients to reduce the rate of new skin cancer development. Neurological complications are managed supportively. Gene therapy and other novel approaches remain under investigation. With strict sun avoidance and vigilant cancer screening, life expectancy can be significantly improved, though patients with neurological involvement generally have a more guarded prognosis.

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