Xeroderma pigmentosum

Last Updated: 2023-07-07

Author(s): Anzengruber F., Navarini A.

ICD11: LD27.1

1/11

Kaposi 1874

Moonlight disease, XP, atrophodermia pigmentosa (Crocker), light-shrinking skin, lioderma essentialis congenita (Auspitz).

Autosomal recessive inherited genodermatosis in which disruption of the nucleotide excision repair system leads to the expression of multiple tumours, premature skin ageing, neurological and ocular diseases.

  • Worldwide
  • Affects all breeds
  • Incidence: 1/250'000/year (Europe)
  • Prevalence: 1/1,000,000 (worldwide)
  • Patients' parents are obligate mutation carriers in one of the XP genes
  • Occurrence already in childhood, first manifestation at ½ - 1 ½ yrs.
  • Females = males
  • Tumours can show as early as 2 yrs

  • Depending on the subtype, there is a different enzymatic defect in DNA repair, which leads to increased sensitivity, especially to UVB. There is an accumulation of somatic mutations in the course, which trigger cutaneous neoplasia.
  • 7 complementation groups A-G as well as XP variant (V)

Repair proteins

 Gene locus Deficiency Function
XP-A 9q22 DNA-damage binding protein 1 Detection of damaged DNA disrupted
XP-B 2q21 Disruption of excision-.repair-cross-complementing-3-gene Deficiency of helicase
XP-C 3p25 Deficiency of endonuclease Detection of damaged DNA disturbed
XP-D 19q13 Deficiency of excision-repair-cross-complementing-2-gene Deficient helicase
XP-E 11p12 Deficiency of DNA-damage binding protein 2 Detection of damaged DNA impaired
XP-F 16ß13 Deficiency of excision-repair-cross-complementing-4-gene à defect of endonuclease Detection of damaged DNA disturbed
XP-G 13q33 Defect of endonuclease Detection of damaged DNA disturbed
XP-V 6p21 Deficiency of DNA polymerase Ɛ Deficiency of postreplication repair of DNA damage

  • Neurological changes
    • In approx. 20%
      • DeSanctis-Cacchione syndrome [1932]
        • Complementation group A patients
        • Severe mental retardation
        • Dwarfism
    • Ocular changes
      • In approx. 40%
      • Keratoconjunctivitis with photophobia, corneal ulceration, ocular neoplasia.
    • XP-A
      • Dermatological symptoms ↑↑↑
      • Mostly there is expression of spinocellular carcinoma
      • Neurological symptoms ↑↑
      • Ocular symptoms ↑↑
    • XP-.B
      • Dermatological symptoms ↑↑↑
      • Mostly there is expression of basal cell carcinoma and spinocellular carcinoma
      • Neurological symptoms ↑
      • Ocular symptoms ↑↑
    • XP-.C
      • Dermatological symptoms ↑
      • Mostly basal cell carcinomas and spinocellular carcinomas occur
      • Neurological symptoms ↑
      • Ocular symptoms -.
    • XP-D
      • Dermatological symptoms ↑↑
      • Mostly malignant melanomas
      • Neurological symptoms ↑↑
      • Ocular symptoms ↑
      • XP-.E
        • Dermatological symptoms ↑
        • Mostly basal cell carcinoma expression
        • Neurological symptoms -
        • Ocular symptoms -
      • XP-F
        • Dermatological symptoms ↑↑
        • Mostly there is expression of basal cell carcinoma and spinocellular carcinoma
        • Neurological symptoms ↑
        • Ocular symptoms -
      • XP-.G
        • Dermatological symptoms ↑↑
        • Mostly there is expression of basal cell carcinoma and spinocellular carcinoma
        • Neurological symptoms ↑
        • Ocular symptoms -.
      • XP-V
        • Dermatological symptoms ↑
        • Mostly there is expression of basal cell carcinoma
        • Neurological symptoms -
        • Ocular symptoms -

  • Histories
    • UV sensitivity (sunburns)
  • Clinical diagnosis
  • Laboratory
    • Determination of complement types
      • Detection of the absence of an endonuclease in fibroblast culture
      • In specialised centres:
      • Measurement of fibroblast survival post-UV exposure
      • Measurement of DNA repair capacity
      • Prenatal diagnosis. in specialised laboratories

Especially sun-exposed areas.

  • ↑ or reduced melanin incorporation (Str. basal, dermal pigment incontinence)
  • Solar elastosis
  • Teleangiectasia
  • Changes corresponding to actinic keratoses, BCC, SCC and MM (in XP-D)

  1. Arlett, C.F. and A.R. Lehmann, Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy: sun sensitivity, DNA repair defects and skin cancer, in Genetic Predisposition to Cancer. 1996, Springer Science + Business Media. p. 185-206.
  2. Blankenburg, S., Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of cutaneous melanoma: a case-control study. Carcinogenesis, 2005. 26(6): p. 1085-1090.
  3. Broughton, B.C., Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene. Human Molecular Genetics, 2001. 10(22): p. 2539-2547.
  4. Cleaver, J.E., Opinion: Cancer in xeroderma pigmentosum and related disorders of DNA repair. Nature Reviews Cancer, 2005. 5(7): p. 564-573.
  5. Cox, S.E., L.J. Roberts, and P.R. Bergstresser, Prevention of skin cancer in xeroderma pigmentosum: The physician as advocate. Journal of the American Academy of Dermatology, 1993. 29(6): p. 1045-1046.
  6. Dilek, F.H., et al., Atypical fibroxanthoma of the skin and the lower lip in xeroderma pigmentosum. Br J Dermatol, 2000. 143(3): p. 618-620.
  7. Dubaele, S., et al., Basal Transcription Defect Discriminates between Xeroderma Pigmentosum and Trichothiodystrophy in XPD Patients. Molecular Cell, 2003. 11(6): p. 1635-1646.
  8. Emmert, B., et al., Xeroderma pigmentosum. Hautarzt, 2011. 62(2): p. 91-97.
  9. Emmert, S., et al., Relationship of Neurologic Degeneration to Genotype in Three Xeroderma Pigmentosum Group G Patients11An abstract of this study was presented at the annual meeting of the Society for Investigative Dermatology, May 2000, Chicago, IL, and published in J Invest Dermatol 114:825, 2000. Journal of Investigative Dermatology, 2002. 118(6): p. 972-982.
  10. Herouy, Y., et al., Xeroderma Pigmentosum: Mondscheinkinder. Xeroderma Pigmentosum: Children of the Moon. Journal der Deutschen Dermatologischen Gesellschaft, 2003. 1(3): p. 191-198.
  11. Johnson, R.E., hRAD30 Mutations in the Variant Form of Xeroderma Pigmentosum. Science, 1999. 285(5425): p. 263-265.
  12. Khan, S.G., Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients. Carcinogenesis, 2005. 27(1): p. 84-94.
  13. Khatri, M.L., M. Shafi, and A. Mashina, Xeroderma pigmentosum. Journal of the American Academy of Dermatology, 1992. 26(1): p. 75-78.
  14. Kraemer, K.H., Xeroderma Pigmentosum. Arch Dermatol, 1987. 123(2): p. 241.
  15. Kraemer, K.H. and J.J. DiGiovanna, Forty years of research on xeroderma pigmentosum at the US National Institutes of Health. Photochem Photobiol, 2015. 91(2): p. 452-9.
  16. Lindenbaum, Y., et al., Xeroderma pigmentosum/Cockayne syndrome complex: first neuropathological study and review of eight other cases. European Journal of Paediatric Neurology, 2001. 5(6): p. 225-242.
  17. Łukasiewicz, Ueber Xeroderma pigmentosum (Kaposi). Arch. f. Dermat., 1895. 33(1): p. 37-67.
  18. Lynch, H.T., Xeroderma Pigmentosum. Arch Dermatol, 1984. 120(2): p. 175.
  19. Mondello, C., et al., Molecular analysis of the XP-D gene in Italian families with patients affected by trichothiodystrophy and xeroderma pigmentosum group D. Mutation Research/DNA Repair, 1994. 314(2): p. 159-165.
  20. Moriwaki, S.-I. and K.H. Kraemer, Xeroderma pigmentosum - bridging a gap between clinic and laboratory. Photodermatology, Photoimmunology & Photomedicine, 2001. 17(2): p. 47-54.
  21. Rapin, I., et al., Cockayne syndrome and xeroderma pigmentosum: DNA repair disorders with overlaps and paradoxes. Neurology, 2000. 55(10): p. 1442-1449.
  22. Shah, P. and Y.Y. He, Molecular regulation of UV-induced DNA repair. Photochem Photobiol, 2015. 91(2): p. 254-64.
  23. Stone, N., et al., Xeroderma pigmentosum: the role of phototesting. Br J Dermatol, 2000. 143(3): p. 595-597.
  24. Wang, Y., et al., Evidence of ultraviolet type mutations in xeroderma pigmentosum melanomas. Proceedings of the National Academy of Sciences, 2009. 106(15): p. 6279-6284.
  25. Yarosh, D., et al., Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. The Lancet, 2001. 357(9260): p. 926-929.
  26. Lebwohl, Mark. Treatment of Skin Disease: Comprehensive Therapeutic Strategies. Elsevier, 2014. Print.