xeroderma pigmentosum

Epidemiology: rare Pathology: - defect in nucleotide excision repair of DNA (except XPV [POLH] variant) - skin cancers - basal cell carcinoma - squamous cell carcinoma - malignant melanomas Genetics: - autosomal recessive - 7 different complementation groups XP-A to XP-G have been identified. - 5 of these genes have been cloned XPAC, XPBC, XPCC, XPDC, XPFC & XPGC - a defect in DDB2 is a cause of XP-E - a defect in POLH (XPV) is associated with mild disease - group A patients (defect in XPAC) show the most severe skin symptoms & progressive neurologic disorder Clinical manifestations: - variable, depending upon genetic defect - may be limited to photo-induced deterioration of the skin & eyes with skin neoplasms at a later age (XPV) - may be serious mutilating disorder - skin - photosensitivity - skin lesions are first noted during infancy or early childhood - sun exposed areas such as the face, neck, hands & arms are most severely involved, but lesions may occur at other sites including the scalp - skin lesions consist of erythema, scaling, bullae, crusting, ephelides, telangiectasia, keratosis, - ocular manifestations - photophobia, lacrimation, blepharitis, symblepharon, keratitis, corneal opacities, tumors of the lids & possible eventual blindness. - neurologic abnormalities - mental deterioration & sensorineural deafness may develop in some patients - syndromes - association of xeroderma pigmentosum with microcephaly, mental retardation, dwarfism & hypogonadism is known as De Santis-Cacchione syndrome - some complementation group XP-B & XP-D patients present with features of Cockayne syndrome - life span is often quite brief Laboratory: - DNA repair defect is detectable in cells cultured from amniotic fluid

General

genetic disease of the skin (genodermatosis) hereditary neoplastic syndrome; cancer susceptibility syndrome progeroid syndrome

Properties

ASSOCIATED-NEOPLASM[S]: squamous cell carcinoma of the skin basal cell carcinoma melanoma

References

Nelson Textbook of Pediatrics, 14th ed., Behrman et al (eds) WB Saunders, Philadelphia, 1992, pg 1651

Databases & Figures

OMIM correlations Human Disorders of DNA Repair