Xeroderma pigmentosum

Xeroderma pigmentosum

Xeroderma pigmentosum is a heterogeneous group of autosomal recessive disorders, characterized by the defective repair of DNA after its damage by ultra-violet radiation. The condition is rare affecting about 5 per million in Europe.

Cause

Ultraviolet light damages DNA by producing covalent linkages between adjacent pyrimidines. These distort the double helix and inhibit gene expression. Cells from xeroderma pigmentosum patients lack the abil-ity of normal cells to repair this damage.

DNA repair is a complex process using a large number of genes that encode a variety of interacting products that locate and prepare damaged sites for excision and replacement. It is not surprising there-fore that many genetic defects can lead to a similar clinical picture. The genes for seven main types of xeroderma pigmentosum have now been identified.

Clinical features

There are many variants but all follow the same pattern.

•   The skin is normal at birth. 

•   Multiple freckles, roughness and keratoses on exposed skin appear between the ages of 6 months and 2 years (Fig. 21.7). Photosensitivity increases thereafter.

•   The atrophic facial skin shows telangiectases and small angiomas.

•   Many tumours develop on light-damaged skin: these include basal cell carcinomas, squamous cell carcino-mas, keratoacanthomas and malignant melanomas. Many patients die before the age of 20 years.

•   Eye problems are common and include photopho-bia, conjunctivitis and ectropion.

•   The condition may be associated with microcephaly, mental deficiency, dwarfism, deafness and ataxia (De Sanctis–Cacchione syndrome).

Diagnosis

This becomes evident on clinical grounds, although variants with minor signs may cause difficulty. The DNA repair defect can be detected in a few laborator-ies after the ultraviolet irradiation of cultured fibrob-lasts or lymphocytes from the patient.

Treatment

Skin cancers can be prevented by strict avoidance of sunlight, the use of protective clothing, wide-brimmed hats and of reflectant sunscreens and dark glasses. If possible, patients should not go out by day. Early and complete removal of all tumours is essential. Radio-therapy should be avoided.