chapter  6
22 Pages

Poikilodermas and aging syndromes

The different types of XP can be subdivided into eight complementation groups related to their different molecular origins, are reported in Table 6.1, but they share the following symptoms:

• Photosensitivity (severe to extreme) • Freckling on photoexposed areas (Figure 6.1)

• Progressive premature aging with poikilodermatous changes (atrophy, lentigo, and telangiectasias) (Figures 6.2 and 6.3)

• Basal cell carcinomas, squamous cell carcinomas and melanoma (in decreasing order) in photoexposed areas, lips, tongue and, rarely, oral and nasal mucosa (Figure 6.4)

• Disfiguring cancer on the face can cause loss of nasal pyramid, orbital structures or external ears, as occurs with repeated surgery (Figures 6.5 and 6.6)

• Rarely, skin angiosarcomas

Extracutaneous findings

• Photophobia, conjunctival cancer, blepharitis, corneal opacities and blindness

• 25% of XP patients show neurologic involvement of different degrees, with low IQ

• Ataxia, abnormal reflex with paresis and progressive central deafness (XP-A) (see Table 6.1)

• Microcephaly, growth retardation and abnormal sexual development in a minority of patients

Genetics and pathogenesis

• XP is inherited as an autosomal recessive disease. • Clinical and cellular photosensitivity is due to

the inability to repair UV-induced DNA damage. Two different DNA-repair processes are defective in XP: the classic nuclear excision repair, divided into two subpathways called the global genome repair system and transcription-coupled repair; and translation synthesis.