FaCD Online Syndrome Fact Sheet

Last updated: 19 Mar 2008

Name: Epidermodysplasia Verruciformis, Familial Clustering of

Mode of Inheritance: AR / AD?/ XLR?

Genes

EVER1, mapped to 17q25
EVER2, mapped to 17q25

Tumor features

skin cancer, squamous cell

Tumor features (possible)

non-Hodgkin lymphoma

Non-tumor features

actinic keratosis
flat red-brown scaly plaques (HPV associated)
flat warts (HPV associated)

Comment

This rare disorder is characterized by the development of two types of Human Papilloma Virus (HPV) associated skin lesions: multiple brown to red scaly plaques (on neck, trunk and proximal extremities, and hundreds of flesh colored flat warts (mainly on acral sites). Malignant transformation of the warts into multiple squamous cell cancer occurs in 25-63 % of the patients.[1;2;3]. Skin cancer occurs at a relatively early age (peak incidence 31-40 years[4], but it has been reported to develop as early as 13 years[2]) Cell-mediated immune response is generally low in these patients. Familial cases of epidermodysplasia verruciformis have been reported. Mode of inheritance is usually autosomal recessive. Bogdan et al[5] reported a family with five children, whereof the father and two sons suffered from EV. The father had a very mild form with only pityriasis versicolor–like macules on the body and no skin cancer. An intestinal diffuse large B cell lymphoma was diagnosed in a 19-year-old male with the disorder[6].

Many different HPV types have been detected in the skin lesions.[1]. Jablonska et al.[7] followed a family with the disorder for 21 years and found that only HPV 4 infected patients developed skin cancer, whereas the HPV 3 associated cases ran a more benign course. However, in a review, Drolet et al.[1] state that HPV 4 has no potential oncogenicity and HPV 5 (the most important one ?), 8, 16 and 18 are detected in epidermodysplasia verrucicans associated squamous cell skin cancer.

References

[1] Drolet BA, Neuburg M, Sanger J. Role of human papillomavirus in cutaneous oncogenesis. Ann Plast Surg 1994; 33(3):339-347.
[2] Lutzner MA. Epidermodysplasia Verruciformis: an autosomal recessive disease characterized by viral warts and skin cancer. A model for viral oncogenesis. Bull Cancer 1978; 65(2):169-182.
[3] Gül U, Kiliç A, Gönül M, Cakmak SK, Bayis SS. Clinical aspects of epidermodysplasia verruciformis and review of the literature. International journal of dermatology 2007; 46(10):1069-72.
[4] Tanigaki T, Kanda R, Yutsudo M, Hakura A. Epidemiologic aspects of epidermodysplasia verruciformis (L-L 1922) in Japan. Jpn J Cancer Res 1986; 77(9):896-900.
[5] Bogdan I, Schärer L, Rüdlinger R, Hafner J. Epidermodysplasia verruciformis in two brothers developing aggressive squamous cell carcinoma. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] 2007; 33(12):1525-8.
[6] Youssef M, Denguezli M, Ghariani N, Belajouza C, Nouira R. Epidermodysplasia verruciformis associated with intestinal lymphoma: a model of viral oncogenicity. Pediatric dermatology 2007 Sep-Oct; 24(5):511-3.
[7] Jablonska S, Orth G, Jarzabek-Chorzelska M, Glinski W, Obalek S, Rzesa G, Croissant O, Favre M. Twenty-one years of follow-up studies of familial epidermodysplasia verruciformis. Dermatologica 1979; 158(5):309-327.