Epidermodysplasia verruciformis (EV) is a rare inherited skin condition in which there is defective immunity to the human papillomavirus (HPV). It usually appears to be recessively inherited, but the genetic basis for the disorder is not entirely clear and in some families, the pattern of inheritance is not consistent with a recessive pattern of inheritance (Robati et al. 2009). In some chronically immunosuppressed patients such as HIV-positive patients, phenocopies may be seen (Jacobelli et al. 2011). Affected individuals develop plane (flat) viral warts in childhood on the trunk and extremities, which evolve into verrucous, polymorphic, warty lesions over time. The appearance of some of the lesions is said to resemble pityriasis versicolor or basal cell papillomas on the trunk and actinic keratoses (precancerous lesions) on exposed sites (Vohra et al. 2010). Ultimately SCC may develop within the warty plaques which may metastasize (Vohra et al. 2010; Kim et al. 2010).
Numerous HPV subtypes have been identified in affected patients, and it is reported that lesions infected with HPV 5 and 8 are more likely to transform, but rarely others are described such as HPV-22b in EV-related SCC (Kim et al. 2010).
The gene associated with recessively inherited EV was mapped to two loci, 2p21-2p24 and 17q25, and subsequently, nonsense mutations in two adjacent novel genes, EVER1 and EVER2, that are associated with the disease were reported at 17p25 (Ramoz et al. 2002). The EVER proteins are expressed by a number of cell types involved in immunity, e.g., dendritic cells and lymphocytes (Rezaei et al. 2011). Twenty-five percent of EV patients have no identifiable mutations in either EVER1 or EVER2 (Orth 2006).