Xeroderma Pigmentosum

Xeroderma pigmentosum (XP) is a rare autosomal recessive genodermatosis that results due to mutations in nucleotide excision repair. The condition characteristically demonstrates severe photosensitivity, skin pigmentary changes, malignant tumor development, and occasionally progressive neurologic degeneration. The disease affects about 1 per million in the United States, and the incidence in Japan is much higher at 45 per million.

Dermatologist Moriz Kaposi first described xeroderma pigmentosum in 1874. Dr. Kaposi described patients with dry skin, pigmentary changes, and the development of multiple skin tumors at a young age. Further studies over the next several decades highlighted the importance of severe photosensitivity in the pathophysiology of xeroderma pigmentosum. In the 1960s, Dr. James Cleaver performed studies on cultured fibroblasts from patients with xeroderma pigmentosum and found the fibroblasts to have defective DNA repair after UV exposure. Further studies showed that patients with xeroderma pigmentosum with neurologic manifestations have even less effective DNA repair after UV exposure compared to patients with XP without neurologic manifestations. These studies have enhanced knowledge about the connections between UV exposure, DNA damage and repair, and the development of malignant tumors.