FaCD Online Syndrome Fact Sheet

Last updated: 06 May 2008

Name: Xeroderma Pigmentosum

Synonym: incl. XPA, XPB, XPC, XPD, XPE, XPF, XPG, XP Variant, XPV

Mode of Inheritance: AR

Genes

DDB2, mapped to 11p12-p11
ERCC2, mapped to 19q13.2-q31.3
ERCC3, mapped to 2q21
ERCC4, mapped to 16p13.3-p13.13
ERCC5, mapped to 13q33
POLH, mapped to 6p12-p21.1
XPA, mapped to 9q22.3-q31
XPC, mapped to 3p25

Tumor features

angiosarcoma
fibroxanthoma
intraoral squamous cell cancer
keratoacanthoma
melanoma, cutaneous
oropharyngeal cancer
skin cancer, basal cell
skin cancer, squamous cell
tongue cancer

Tumor features (possible)

astrocytoma
fibrosarcoma
malignant fibrous histiocytoma
renal leiomyosarcoma
schwannoma (neurilemmoma), cranial nerve
Wilms' tumor (nephroblastoma)

Non-tumor features

actinic keratosis
conjunctivitis
cutaneous telangiectasia
developmental delay/mental deficiency/mental retardation
hearing loss, neurosensory
hyperpigmentation of the skin
hypopigmentation of the skin
increased chromosomal breakage
microcephaly
mutagen sensitivity, increased
neurological degeneration, general
oculocutaneous telangiectasia
oropharyngeal leukoplakia
testicles, small
UV hypersensitivity
UV radiation sensitivity, increased

Comment

This is a heterogeneous group of disorders: subdivided into a number of subtypes: complementation groups A-G and XPV, together XPA and XPC account for approximately half of XP cases. Typical shared symptoms are sunlight (UV) sensitivity: photophobia, conjunctivitis (developing during early childhood) and later pigmented and achromic macules, actinic keratosis, cutaneous telangiectasia, and the development of (early onset) basal cell cancer, squamous cell cancer, melanoma and keratoacanthoma.[2].

In the 10-14 year age group 50 % of the XP patients has skin neoplasms, the median age of onset of non-melanoma skin cancer is under the age of ten years. Melanomas have been reported in 5 % of cases.[2]. Other tumors that have been reported: angiosarcoma[3-6], intraoral squamous cell cancer and leukoplakia[7-9], fibroxanthoma[10-12], schwannoma [13], spinal cord astrocytoma[14], malignant fibrous histiocytoma[15], renal leiomyosarcoma[16] and adult Wilms tumor[17].

Patients from the XPA and XPD complementation groups are also prone to develop neurological complications due to premature neuronal death: including mental retardation, ataxia, choreoathetosis, quadriparesis and sensineuronal deafness. In general, XP patients have shortened life expectancy (they die on average 30 years earlier than the general population).

XP Variant (XPV) patients have sun sensitivity and increased skin cancer risk and complications with neurological abnormalities are extremely rare. XPV cells have normal nucleotide excision repair, normal unscheduled DNA synthesis, decrease in post-UV survival in the presence of caffeine and have bi-allelic germline defects in the POLH gene[18-20]. XPV patients generally do not develop clinical manifestations, including skin cancer, until a later age, but early symptoms as in other XP types have been reported. In a Japanese cohort of XPV patients, the average age of onset of skin cancer was 45 years[20]. Some authors have suggested that XPV predisposes to internal malignancies as well[21].

Links

The Xeroderma Pigmentosum Society, Inc. (XPS) 24 1 08

References

[1] Dworaczek H, Xiao W. Xeroderma pigmentosum: a glimpse into nucleotide excision repair, genetic instability, and cancer. Critical reviews in oncogenesis 2007; 13(2):159-77.
[2] Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum:Cutaneous, ocular and neurologic abnormalities in 830 published cases. Arch Dermatol 1987; 123:241-250.
[3] De Silva BD, Nawroz I, Doherty VR. Angiosarcoma of the head and neck associated with xeroderma pigmentosum variant [letter]. Br J Dermatol 1999; 141(1):166-167.
[4] Marcon I, Collini P, Casanova M, Meazza C, Ferrari A. Cutaneous angiosarcoma in a patient with xeroderma pigmentosum. Pediatric hematology and oncology 2004 Jan-Feb; 21(1):23-6.
[5] Ludolph-Hauser D, Thoma-Greber E, Sander C, Sommerhoff CP, Röcken M. Mast cells in an angiosarcoma complicating xeroderma pigmentosum in a 13-year-old girl. Journal of the American Academy of Dermatology 2000; 43(5 Pt 2):900-2.
[6] Leake J, Sheehan MP, Rampling D, Ramani P, Atherton DJ. Angiosarcoma complicating xeroderma pigmentosum. Histopathology 1992; 21(2):179-81.
[7] Keukens F, van Voorst Vader PC, Panders AK, Vinks S, Oosterhuis JW, Kleijer WJ. Xeroderma pigmentosum: squamous cell carcinoma of the tongue. Acta dermato-venereologica 1989; 69(6):530-1.
[8] Huet-Lamy P, Dereure O, Degavre B, Atlan PY, Guillot B, Guilhou JJ. [Carcinoma of the tongue in xeroderma pigmentosum]. Annales de dermatologie et de vénéréologie 1992; 119(12):980-2.
[9] Wade MH, Plotnick H. Xeroderma pigmentosum and squamous cell carcinoma of the tongue. Identification of two black patients as members of complementation group C. Journal of the American Academy of Dermatology 1985; 12(3):515-21.
[10] Youssef N, Vabres P, Buisson T, Brousse N, Fraitag S. Two unusual tumors in a patient with xeroderma pigmentosum: atypical fibroxanthoma and basosquamous carcinoma. Journal of cutaneous pathology 1999; 26(9):430-5.
[11] Shao L, Newell B, Quintanilla N. Atypical fibroxanthoma and squamous cell carcinoma of the conjunctiva in xeroderma pigmentosum. Pediatric and developmental pathology 2007 Mar-Apr; 10(2):149-52.
[12] Dilek FH, Akpolat N, Metin A, Ugras S. Atypical fibroxanthoma of the skin and the lower lip in xeroderma pigmentosum. The British journal of dermatology 2000; 143(3):618-20.
[13] Nakamura T, Ono T, Yoshimura K, Arao T, Kondo S, Ichihashi M, Matsumoto A, Fujiwara Y. Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D. Journal of the American Academy of Dermatology 1991; 25(2 Pt 2):349-53.
[14] DiGiovanna JJ, Patronas N, Katz D, Abangan D, Kraemer KH. Xeroderma pigmentosum: spinal cord astrocytoma with 9-year survival after radiation and isotretinoin therapy. Journal of cutaneous medicine and surgery 1998; 2(3):153-8.
[15] Pe'er J, Levinger S, Chirambo M, Ron N, Okon E. Malignant fibrous histiocytoma of the skin and the conjunctiva in xeroderma pigmentosum. Archives of pathology & laboratory medicine 1991; 115(9):910-4.
[16] Tomás M, Salinas AS, Moreno J, Server G. Renal leiomyosarcoma associated with xeroderma pigmentosum. Archivos españoles de urología 1989; 42(5):484-6.
[17] Visweswara RN, Osman AR, Majeed SA, Sherghin AS, Muttardi MA. Xeroderma pigmentosum with adult Wilms' tumour. A rare association. Scandinavian journal of urology and nephrology 1997; 31(6):569-71.
[18] Gratchev A, Strein P, Utikal J, Sergij G. Molecular genetics of Xeroderma pigmentosum variant. Experimental dermatology 2003; 12(5):529-36.
[19] Inui H, Oh KS, Nadem C, Ueda T, Khan SG, Metin A, Gozukara E, Emmert S, Slor H, Busch DB, Baker CC, Digiovanna JJ, Tamura D, Seitz CS, Gratchev A, Wu WH, Chung KY, Chung HJ, Azizi E, Woodgate R, Schneider TD, Kraemer KH. Xeroderma Pigmentosum-Variant Patients from America, Europe, and Asia. The Journal of investigative dermatology 2008; Epub ahead of print.
[20] Tanioka M, Masaki T, Ono R, Nagano T, Otoshi-Honda E, Matsumura Y, Takigawa M, Inui H, Miyachi Y, Moriwaki S, Nishigori C. Molecular analysis of DNA polymerase eta gene in Japanese patients diagnosed as xeroderma pigmentosum variant type. The Journal of investigative dermatology 2007; 127(7):1745-51.
[21] Kuwamoto K, Miyauchi-Hashimoto H, Isei T, Horio T. Xeroderma pigmentosum variant associated with multiple cancers. Photodermatology, photoimmunology & photomedicine 1999 Jun-Aug; 15(3-4):127-32.