Skip to main content
SpringerLink
Log in

Management of Xeroderma Pigmentosum

  • Chapter
  • First Online:
DNA Repair Disorders

  • 745 Accesses

Abstract

Xeroderma pigmentosum (XP) is a rare, autosomal recessive inherited disease of DNA repair with a high incidence of sunlight-induced cancer of the skin and eye. Approximately half of the patients have marked burning on minimal sun exposure, often resulting in severe blistering in infancy. The other XP patients do not have this exquisite photosensitivity but develop freckle-like pigmentation of the face and other sun exposed sites, frequently before 2 years of age. Overall, XP patients have a more than 10,000-fold increase in frequency of basal cell or squamous cell carcinoma of the skin with a median age of onset of less than 10 years, nearly 60 years younger than in the US general population. There is a similar high frequency of skin melanoma, but the median age is 22 years, which is 33 years younger than in the US general population. About 25% of the XP patients have progressive neurological degeneration, often first appearing as diminished deep tendon reflexes, microcephaly, and high-frequency sensorineural hearing loss. Early recognition of neurological involvement permits use of hearing aids and other assistive devices. Management is based on early diagnosis, rigorous sun protection, and early detection and treatment of skin cancers. Oral retinoids have been demonstrated to prevent new skin cancers but have numerous side effects. Newer therapies such as use of topical bacterial DNA repair enzymes, correction of the DNA repair defect in cultured cells, and topical agents to increase read-through of premature stop codons are under investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kleijer WJ, Laugel V, Berneburg M, Nardo T, Fawcett H, Gratchev A, et al. Incidence of DNA repair deficiency disorders in western Europe: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. DNA Repair (Amst). 2008;7(5):744–50.

    Article  CAS  Google Scholar 

  2. Cartault F, Nava C, Malbrunot AC, Munier P, Hebert JC, N’Guyen P, et al. A new XPC gene splicing mutation has lead to the highest worldwide prevalence of xeroderma pigmentosum in black Mahori patients. DNA Repair (Amst). 2011;10(6):577–85.

    Article  CAS  Google Scholar 

  3. Nakano E, Masaki T, Kanda F, Ono R, Takeuchi S, Moriwaki S, et al. The present status of xeroderma pigmentosum in Japan and a tentative severity classification scale. Exp Dermatol. 2016;25(Suppl 3):28–33.

    Article  PubMed  Google Scholar 

  4. Doubaj Y, Laarabi FZ, Elalaoui SC, Barkat A, Sefiani A. Carrier frequency of the recurrent mutation c.1643_1644delTG in the XPC gene and birth prevalence of the xeroderma pigmentosum in Morocco. J Dermatol. 2012;39(4):382–4.

    Article  CAS  PubMed  Google Scholar 

  5. Kraemer KH, Lee MM, Andrews AD, Lambert WC. The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm. Arch Dermatol. 1994;130(8):1018–21.

    Article  CAS  PubMed  Google Scholar 

  6. DiGiovanna JJ, Kraemer KH. Shining a light on xeroderma pigmentosum. J Invest Dermatol. 2012;132(3 Pt 2):785–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bradford PT, Goldstein AM, Tamura D, Khan SG, Ueda T, Boyle J, et al. Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair. J Med Genet. 2011;48(3):168–76.

    Article  PubMed  Google Scholar 

  8. Emmert S, Ueda T, Zumsteg U, Weber P, Khan SG, Oh KS, et al. Strict sun protection results in minimal skin changes in a patient with xeroderma pigmentosum and a novel c.2009delG mutation in XPD (ERCC2). Exp Dermatol. 2009;18(1):64–8.

    Article  CAS  PubMed  Google Scholar 

  9. Tamura D, Khan SG, Merideth M, DiGiovanna JJ, Tucker MA, Goldstein AM, et al. Effect of mutations in XPD(ERCC2) on pregnancy and prenatal development in mothers of patients with trichothiodystrophy or xeroderma pigmentosum. Eur J Hum Genet. 2012;20(12):1308–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fassihi H. Importance of genotype-phenotype correlation in xeroderma pigmentosum. Br J Dermatol. 2015;172(4):859–60.

    Article  CAS  PubMed  Google Scholar 

  11. Fassihi H, Sethi M, Fawcett H, Wing J, Chandler N, Mohammed S, et al. Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect. Proc Natl Acad Sci U S A. 2016;113(9):E1236–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol. 1987;123(2):241–50.

    Article  CAS  PubMed  Google Scholar 

  13. Giarelli E, Jacobs LA. Modifying cancer risk factors: the gene-environment interaction. Semin Oncol Nurs. 2005;21(4):271–7.

    Article  PubMed  Google Scholar 

  14. Kraemer KH. Xeroderma pigmentosum. A prototype disease of environmental-genetic interaction. Arch Dermatol. 1980;116(5):541–2.

    Article  CAS  PubMed  Google Scholar 

  15. Almeida HL, Kopp J, Jorge VM, Sartori DS, Velloso CD. Extensive hydroa vacciniforme. An Bras Dermatol. 2013;88(4):620–2.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Andersen J, Gjengedal E, Sandberg S, Raheim M. A skin disease, a blood disease or something in between? An exploratory focus group study of patients’ experiences with porphyria cutanea tarda. Br J Dermatol. 2015;172(1):223–9.

    Article  CAS  PubMed  Google Scholar 

  17. Fassihi H. Spotlight on xeroderma pigmentosum. Photochem Photobiol Sci. 2013;12(1):78–84.

    Article  CAS  PubMed  Google Scholar 

  18. Milota M, Jones DL, Cleaver J, Jamall IS. Xeroderma pigmentosum family support group: helping families and promoting clinical initiatives. DNA Repair (Amst). 2011;10(7):792–7.

    Article  CAS  Google Scholar 

  19. Duarte I, Rotter A, Malvestiti A, Silva M. The role of glass as a barrier against the transmission of ultraviolet radiation: an experimental study. Photodermatol Photoimmunol Photomed. 2009;25(4):181–4.

    Article  PubMed  Google Scholar 

  20. Tamura D, DiGiovanna JJ, Khan SG, Kraemer KH. Living with xeroderma pigmentosum: comprehensive photoprotection for highly photosensitive patients. Photodermatol Photoimmunol Photomed. 2014;30(2–3):146–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Davis BE, Koh HK, Rohrer TE, Gonzalez E, Cleaver JE. Sunlight avoidance and cancer prevention in xeroderma pigmentosum. Arch Dermatol. 1994;130(6):806–8.

    Article  CAS  PubMed  Google Scholar 

  22. Webb S. Xeroderma pigmentosum. BMJ. 2008;336(7641):444–6.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lim HW, Arellano-Mendoza MI, Stengel F. Current challenges in photoprotection. J Am Acad Dermatol. 2017;76(3S1):S91–S9.

    Article  CAS  PubMed  Google Scholar 

  24. Ramkumar HL, Brooks BP, Cao X, Tamura D, Digiovanna JJ, Kraemer KH, et al. Ophthalmic manifestations and histopathology of xeroderma pigmentosum: two clinicopathological cases and a review of the literature. Surv Ophthalmol. 2011;56(4):348–61.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Dollfus H, Porto F, Caussade P, Speeg-Schatz C, Sahel J, Grosshans E, et al. Ocular manifestations in the inherited DNA repair disorders. Surv Ophthalmol. 2003;48(1):107–22.

    Article  PubMed  Google Scholar 

  26. Brooks BP, Thompson AH, Bishop RJ, Clayton JA, Chan CC, Tsilou ET, et al. Ocular manifestations of xeroderma pigmentosum: long-term follow-up highlights the role of DNA repair in protection from sun damage. Ophthalmology. 2013;120(7):1324–36.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mahindra P, DiGiovanna JJ, Tamura D, Brahim JS, Hornyak TJ, Stern JB, et al. Skin cancers, blindness, and anterior tongue mass in African brothers. J Am Acad Dermatol. 2008;59(5):881–6.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Olson MT, Puttgen KB, Westra WH. Angiosarcoma arising from the tongue of an 11-year-old girl with xeroderma pigmentosum. Head Neck Pathol. 2012;6(2):255–7.

    Article  PubMed  Google Scholar 

  29. Behan JW, Sutton A, Wysong A. Management of skin cancer in the high-risk patient. Curr Treat Options Oncol. 2016;17(12):60.

    Article  PubMed  Google Scholar 

  30. Cerio R. The importance of patient-centred care to overcome barriers in the management of actinic keratosis. J Eur Acad Dermatol Venereol. 2017;31(Suppl 2):17–20.

    Article  PubMed  Google Scholar 

  31. Lambert WC, Lambert MW. Development of effective skin cancer treatment and prevention in xeroderma pigmentosum. Photochem Photobiol. 2015;91(2):475–83.

    Article  CAS  PubMed  Google Scholar 

  32. Giannotti B, Vanzi L, Difonzo EM, Pimpinelli N. The treatment of basal cell carcinomas in a patient with xeroderma pigmentosum with a combination of imiquimod 5% cream and oral acitretin. Clin Exp Dermatol. 2003;28(Suppl 1):33–5.

    Article  PubMed  Google Scholar 

  33. Goldenberg G. Treatment considerations in actinic keratosis. J Eur Acad Dermatol Venereol. 2017;31(Suppl 2):12–6.

    Article  PubMed  Google Scholar 

  34. Gupta AK, Paquet M, Villanueva E, Brintnell W. Interventions for actinic keratoses. Cochrane Database Syst Rev. 2012;12:CD004415.

    PubMed  Google Scholar 

  35. Roseeuw D. The treatment of basal skin carcinomas in two sisters with xeroderma pigmentosum. Clin Exp Dermatol. 2003;28(Suppl 1):30–2.

    Article  PubMed  Google Scholar 

  36. Stockfleth E. The importance of treating the field in actinic keratosis. J Eur Acad Dermatol Venereol. 2017;31(Suppl 2):8–11.

    Article  PubMed  Google Scholar 

  37. Walker JL, Siegel JA, Sachar M, Pomerantz H, Chen SC, Swetter SM, et al. 5-fluorouracil for actinic keratosis treatment and chemoprevention: a randomized controlled trial. J Invest Dermatol. 2017;137(6):1367–70.

    Article  CAS  PubMed  Google Scholar 

  38. Yang JQ, Chen XY, Engle MY, Wang JY. Multiple facial basal cell carcinomas in xeroderma pigmentosum treated with topical imiquimod 5% cream. Dermatol Ther. 2015;28(4):243–7.

    Article  PubMed  Google Scholar 

  39. Larson DM, Cunningham BB. Photodynamic therapy in a teenage girl with xeroderma pigmentosum type C. Pediatr Dermatol. 2012;29(3):373–4.

    Article  PubMed  Google Scholar 

  40. Brooks PJ, Wise DS, Berry DA, Kosmoski JV, Smerdon MJ, Somers RL, et al. The oxidative DNA lesion 8,5′-(S)-cyclo-2′-deoxyadenosine is repaired by the nucleotide excision repair pathway and blocks gene expression in mammalian cells. J Biol Chem. 2000;275(29):22355–62.

    Article  CAS  PubMed  Google Scholar 

  41. Besaratinia A, Bates SE, Synold TW, Pfeifer GP. Similar mutagenicity of photoactivated porphyrins and ultraviolet A radiation in mouse embryonic fibroblasts: involvement of oxidative DNA lesions in mutagenesis. Biochemistry. 2004;43(49):15557–66.

    Article  CAS  PubMed  Google Scholar 

  42. Kraemer KH, DiGiovanna JJ, Moshell AN, Tarone RE, Peck GL. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med. 1988;318(25):1633–7.

    Article  CAS  PubMed  Google Scholar 

  43. Campbell RM, DiGiovanna JJ. Skin cancer chemoprevention with systemic retinoids: an adjunct in the management of selected high-risk patients. Dermatol Ther. 2006;19(5):306–14.

    Article  PubMed  Google Scholar 

  44. DiGiovanna JJ. Retinoid chemoprevention in the high-risk patient. J Am Acad Dermatol. 1998;39(2 Pt 3):S82–5.

    Article  CAS  PubMed  Google Scholar 

  45. Nelson BR, Fader DJ, Gillard M, Baker SR, Johnson TM. The role of dermabrasion and chemical peels in the treatment of patients with xeroderma pigmentosum. J Am Acad Dermatol. 1995;32(4):623–6.

    Article  CAS  PubMed  Google Scholar 

  46. Sibar S, Findikcioglu K, Erdal AI, Barut I, Ozmen S. Technical aspects and difficulties in the management of head and neck cutaneous malignancies in xeroderma pigmentosum. Arch Plast Surg. 2016;43(4):344–51.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Hoorens I, Batteauw A, Van Maele G, Lapiere K, Boone B, Ongenae K. Mohs micrographic surgery for basal cell carcinoma: evaluation of the indication criteria and predictive factors for extensive subclinical spread. Br J Dermatol. 2016;174(4):847–52.

    Article  CAS  PubMed  Google Scholar 

  48. van Leeuwen AC, The A, Moolenburgh SE, de Haas ER, Mureau MA. A retrospective review of reconstructive options and outcomes of 202 cases large facial Mohs micrographic surgical defects, based on the aesthetic unit involved. J Cutan Med Surg. 2015;19(6):580–7.

    Article  PubMed  CAS  Google Scholar 

  49. Tayeb T, Laure B, Sury F, Lorette G, Goga D. Facial resurfacing with split-thickness skin grafts in xeroderma pigmentosum variant. J Craniomaxillofac Surg. 2011;39(7):496–8.

    Article  PubMed  Google Scholar 

  50. Cox SE, Roberts LJ, Bergstresser PR. Prevention of skin cancer in xeroderma pigmentosum: the physician as advocate. J Am Acad Dermatol. 1993;29(6):1045–6.

    Article  CAS  PubMed  Google Scholar 

  51. Alfawaz AM, Al-Hussain HM. Ocular manifestations of xeroderma pigmentosum at a tertiary eye care center in Saudi Arabia. Ophthal Plast Reconstr Surg. 2011;27(6):401–4.

    Article  PubMed  Google Scholar 

  52. Lim R, Fedele F, Patel P, Morley AM. Ocular solar protection in xeroderma pigmentosum: the role of untinted lenses in blocking ultraviolet radiation. Br J Dermatol. 2016;175(3):625–7.

    Article  CAS  PubMed  Google Scholar 

  53. Jalali S, Boghani S, Vemuganti GK, Ratnakar KS, Rao GN. Penetrating keratoplasty in xeroderma pigmentosum. Case reports and review of the literature. Cornea. 1994;13(6):527–33.

    Article  CAS  PubMed  Google Scholar 

  54. Brooks PJ. DNA repair in neural cells: basic science and clinical implications. Mutat Res. 2002;509(1–2):93–108.

    Article  CAS  PubMed  Google Scholar 

  55. Brooks PJ. The cyclopurine deoxynucleosides: DNA repair, biological effects, mechanistic insights, and unanswered questions. Free Radic Biol Med. 2017;107:90–100.

    Article  CAS  PubMed  Google Scholar 

  56. Robbins JH. A childhood neurodegeneration due to defective DNA repair: a novel concept of disease based on studies xeroderma pigmentosum. J Child Neurol. 1989;4(2):143–6.

    Article  CAS  PubMed  Google Scholar 

  57. Robbins JH, Brumback RA, Mendiones M, Barrett SF, Carl JR, Cho S, et al. Neurological disease in xeroderma pigmentosum. Documentation of a late onset type of the juvenile onset form. Brain. 1991;114(Pt 3):1335–61.

    Article  PubMed  Google Scholar 

  58. Davies H. Living with dying: families coping with a child who has a neurodegenerative genetic disorder. Axone. 1996;18(2):38–44.

    CAS  PubMed  Google Scholar 

  59. Totonchy MB, Tamura D, Pantell MS, Zalewski C, Bradford PT, Merchant SN, et al. Auditory analysis of xeroderma pigmentosum 1971-2012: hearing function, sun sensitivity and DNA repair predict neurological degeneration. Brain. 2013;136(Pt 1):194–208.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Kraemer KH, DiGiovanna JJ. Forty years of research on xeroderma pigmentosum at the US National Institutes of Health. Photochem Photobiol. 2015;91(2):452–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Yarosh D, Klein J, O’Connor A, Hawk J, Rafal E, Wolf P. Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group. Lancet. 2001;357(9260):926–9.

    Article  CAS  PubMed  Google Scholar 

  62. Warrick E, Garcia M, Chagnoleau C, Chevallier O, Bergoglio V, Sartori D, et al. Preclinical corrective gene transfer in xeroderma pigmentosum human skin stem cells. Mol Ther. 2012;20(4):798–807.

    Article  CAS  PubMed  Google Scholar 

  63. Dupuy A, Valton J, Leduc S, Armier J, Galetto R, Gouble A, et al. Targeted gene therapy of xeroderma pigmentosum cells using meganuclease and TALEN. PLoS One. 2013;8(11):e78678.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Kuschal C, DiGiovanna JJ, Khan SG, Gatti RA, Kraemer KH. Repair of UV photolesions in xeroderma pigmentosum group C cells induced by translational read-through of premature termination codons. Proc Natl Acad Sci U S A. 2013;110(48):19483–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kuschal C, Khan SG, Enk B, DiGiovanna JJ, Kraemer KH. Readthrough of stop codons by use of aminoglycosides in cells from xeroderma pigmentosum group C patients. Exp Dermatol. 2015;24(4):296–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ono R, Khan S, Kuschal C, Tamura D, Chen J, Luo X, DiGiovanna JJ, Kraemer KH. Induced DNA repair in xeroderma pigmentosum group C cells by read-through of premature termination codons. J Investig Dermatol. 2017;137(5S):S117.

    Article  Google Scholar 

  67. Levenson D. Communication with parents counts. Am J Med Genet A. 2010;152A(5):fmvii–fmix.

    Article  PubMed  Google Scholar 

  68. Riley C, Rubarth LB. Supporting families of children with disabilities. J Obstet Gynecol Neonatal Nurs. 2015;44(4):536–42.

    Article  PubMed  Google Scholar 

  69. Rupp K, Davies PS, Newcomb C, Iams H, Becker C, Mulpuru S, et al. A profile of children with disabilities receiving SSI: highlights from the National Survey of SSI Children and Families. Soc Secur Bull. 2005;66(2):21–48.

    PubMed  Google Scholar 

  70. Joachim G, Acorn S. Living with chronic illness: the interface of stigma and normalization. Can J Nurs Res. 2000;32(3):37–48.

    CAS  PubMed  Google Scholar 

  71. Austin A, Herrick H, Proescholdbell S, Simmons J. Disability and exposure to high levels of adverse childhood experiences: effect on health and risk behavior. N C Med J. 2016;77(1):30–6.

    PubMed  Google Scholar 

  72. Deatrick JA, Knafl KA, Murphy-Moore C. Clarifying the concept of normalization. Image J Nurs Schloarsh. 1999;31(3):209–14.

    Article  CAS  Google Scholar 

  73. Silverman AM, Molton IR, Smith AE, Jensen MP, Cohen GL. Solace in solidarity: disability friendship networks buffer well-being. Rehabil Psychol. 2017;62(4):525–33.

    Article  PubMed  Google Scholar 

  74. Janson K, Law M. Siblings of children with special needs. Phys Occup Ther Pediatr. 2002;22(1):73–8.

    Article  PubMed  Google Scholar 

  75. Pit-Ten Cate IM, Loots GM. Experiences of siblings of children with physical disabilities: an empirical investigation. Disabil Rehabil. 2000;22(9):399–408.

    Article  CAS  PubMed  Google Scholar 

  76. Lai JP, Liu YC, Alimchandani M, Liu Q, Aung PP, Matsuda K, et al. The influence of DNA repair on neurological degeneration, cachexia, skin cancer and internal neoplasms: autopsy report of four xeroderma pigmentosum patients (XP-A, XP-C and XP-D). Acta Neuropathol Commun. 2013;1:4.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank the XP patients and their families for participation in our research studies.

Author information

Authors and Affiliations

  1. Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    Deborah Tamura, Ryusuke Ono, John J. DiGiovanna & Kenneth H. Kraemer

Authors
  1. Deborah Tamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryusuke Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John J. DiGiovanna
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenneth H. Kraemer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenneth H. Kraemer .

Editor information

Editors and Affiliations

  1. Department of Dermatology, Graduate School of Medicine, Kobe University, Kobe, Japan

    Chikako Nishigori

  2. Biosignal Research Center, Kobe University, Kobe, Japan

    Kaoru Sugasawa

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Tamura, D., Ono, R., DiGiovanna, J.J., Kraemer, K.H. (2019). Management of Xeroderma Pigmentosum. In: Nishigori, C., Sugasawa, K. (eds) DNA Repair Disorders. Springer, Singapore. https://doi.org/10.1007/978-981-10-6722-8_14

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-6722-8_14

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-6721-1

  • Online ISBN: 978-981-10-6722-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation