OBSOLETE: Xeroderma pigmentosum complementation group D

Xeroderma pigmentosum complementation group D (XP-D) is an autosomal recessive disorder caused by mutations in the ERCC2 (XPD) gene, which encodes a helicase involved in nucleotide excision repair (NER) and transcription. This Orphanet entry (276258) is designated as OBSOLETE, meaning it has been retired and its clinical content has been merged into other active disease entries. XP-D is now typically classified under the broader entry for xeroderma pigmentosum or under specific phenotypic categories associated with ERCC2 mutations, which can include classic xeroderma pigmentosum, XP with neurological disease, trichothiodystrophy, or cerebro-oculo-facio-skeletal syndrome, depending on the nature of the mutation. In its classic xeroderma pigmentosum presentation, XP-D affects primarily the skin, eyes, and nervous system. Patients develop extreme sensitivity to ultraviolet (UV) radiation, leading to severe sunburns, freckling, and a dramatically increased risk of skin cancers (basal cell carcinoma, squamous cell carcinoma, and melanoma) at a very young age. Ocular manifestations include photophobia, keratitis, and potential malignancies of the eye. A subset of XP-D patients also develops progressive neurological degeneration, including sensorineural hearing loss, cognitive decline, and peripheral neuropathy. Management is primarily preventive, focusing on rigorous UV protection, regular dermatological surveillance, early excision of skin cancers, and ophthalmologic monitoring. There is currently no curative treatment, though gene therapy approaches are under investigation.

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