OBSOLETE: Xeroderma pigmentosum complementation group E

Xeroderma pigmentosum complementation group E (XP-E) is a rare autosomal recessive disorder of DNA repair, specifically affecting the nucleotide excision repair (NER) pathway. This Orphanet entry (276261) is marked as OBSOLETE, meaning it has been retired and its content has been merged into or replaced by another entry within the Orphanet classification system, typically the broader xeroderma pigmentosum entry. XP-E is caused by biallelic pathogenic variants in the DDB2 gene (also known as XPE), which encodes the DNA damage-binding protein 2, a key component in the recognition of UV-induced DNA lesions. Xeroderma pigmentosum group E is generally considered one of the milder forms of XP. Affected individuals develop extreme sensitivity to ultraviolet (UV) radiation, leading to sunburn with minimal sun exposure, freckling and pigmentary changes in sun-exposed skin beginning in early childhood, and a markedly elevated risk of skin cancers including basal cell carcinoma, squamous cell carcinoma, and melanoma. Unlike some other XP complementation groups, XP-E patients typically do not develop the severe neurological degeneration seen in groups A, B, or D, though mild neurological findings have occasionally been reported. Management of XP-E centers on rigorous sun protection, including UV-blocking clothing, broad-spectrum sunscreen, UV-filtering eyewear, and avoidance of sun exposure. Regular dermatological surveillance for early detection and treatment of premalignant and malignant skin lesions is essential. Ophthalmological monitoring is also recommended, as the eyes can be affected by UV damage. There is currently no cure or gene-specific therapy available, and treatment remains supportive and preventive.

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