Xeroderma pigmentosum variant with multisystem involvement.

Abstract

BACKGROUND: Xeroderma pigmentosum (XP) is a hereditary disorder characterized by recessive inheritance and elevated rates of skin carcinogenesis. There are seven complementation groups (A through G) for which the genetic defect results in a failure to repair DNA damage from UV light and sunlight; one group, the variant, fails to replicate UV-damaged DNA correctly. Patients in XP groups A, B, D, and G have associated neurologic problems, the most severe being known as the DeSanctis-Cacchione syndrome. OBSERVATIONS: We describe a patient with XP from consanguineous parents who has severe multisystem involvement similar to that of the DeSanctis-Cacchione syndrome. Extensive laboratory investigation showed that cells from this patient exhibit DNA replication after irradiation with UV light that is characteristic of the XP variant. The cells also show normal sensitivity to UV light and normal excision repair, consistent with XP variant classification. The presence of the neurologic symptoms is quite unusual in an XP variant. CONCLUSION: Our patient clearly fits into the XP variant category based on normal survival, caffeine toxic reaction, photoproduct excision and repair, and the deficient replication of UV-damaged DNA. This patient seems to be rare, however, among XP variants in displaying severe neurologic symptoms. Because of the consanguineous parents, the possibility that some of this patient's findings are from non-XP-related abnormalities must also be entertained. However, other consanguineous patients with XP variant, eg, XPIOCA, have been described who do not show neurologic abnormalities. In view of the difficulty of defining an XP group from clinical symptoms alone, we urge the term xeroderma pigmentosum variant be used only in the context of the laboratory studies of patients with XP that contain normal repair but deficient semiconservative replication of UV-damaged DNA.