Xeroderma pigmentosum (OMIM #278700, #278720, #278730, #278740, #278750, #610651) is a genetic disease in which a defect in the DNA repair system prevents DNA damage caused by UV radiation from being detected and repaired, resulting in a high risk of tumor development in skin exposed to sunlight.

Key Data

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Synonym XP, melanosis lenticularis progressiva
Gene products DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, POLH, XPA, XPC
Function Detection of UV-induced DNA damage and global genome repair
Heredity Autosomal recessive
Prevalence 1:1,000,000 in the USA and Europe, slightly elevated incidence in the Middle East, Japan, and North Africa
Genotype-phenotype correlation A genotype-phenotype correlation study is currently underway.
Penetrance High
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An integrated examination of the typical clinical symptoms and family history and/or molecular genetic evidence of biallelic pathogenic variants in DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, POLH, XPA, or XPC


Genetic evidence can be confirmed by single-gene testing. The use of panel examinations consisting of multiple genes together with exome or genome sequencing may also be helpful.

Basic Variant After Localization

  • XPA

    • India: c.335_338delTTATinsCATAAGAAA
    • Japan: c.390-1G>C (carrier incidence of 1%)
    • Tunisia: p.Arg228Ter
  • XPC

    • North Africa: c.1643_1644delTG
  • ERCC2

    • Iraqi Jews: p.Arg683Gln
  • POLH

    • Tunisia / North Africa: Del exon 10
    • Japan: c.490G>T (splice site variant); p.Ser242Ter; p.Glu306Ter and c.1661delA
    • Basque region / North Spain: c.764+1G>A

Differential Diagnoses

  • Genetic syndrome with increased cutaneous photosensitivity due to a defective nucleotide excision repair system (NER):

    • XP with neurological abnormalities
    • Cockayne syndrome (CS)
    • XP/CS complex
    • Trichothiodystrophy (TTD)
    • XP/TTD complex
    • Cerebro-oculo-facio-skeletal (COFS) syndrome
    • COFS/TTD complex
    • CS/TTD complex
    • UV-sensitive syndrome
  • Baller-Gerold Syndrome

  • Carney Complex

Clinical Presentation

Clinical Presentation

  • Increased sensitivity to sun exposure (severe sunburn with blistering, erythema formation after only minimal exposure to sunlight in around 60% of patients), freckle-like pigmentation changes in the face before the age of 2

  • Sunlight-related eye problems (photophobia, keratitis, eyelid skin atrophy)

  • Greatly increased risk of developing cutaneous neoplasia related to sunlight exposure (basal cell carcinomas, squamous epithelial carcinomas, melanomas)

  • Rare, severe neurological complications (progressive sensorineural hearing loss, cognitive impairment)

Predisposition to Cancer

  • Basal cell carcinomas

  • Melanomas

  • Squamous epithelial carcinomas (face, head, and neck region)

  • Leukemia

  • Cerebral and spinal gliomas

  • Other solid tumors (lungs, uterus, breasts, pancreas, kidneys, stomach, testicles)

Therapeutic Considerations

  • Dietary supplementation with oral vitamin D if there is a deficit

  • Avoiding exposure to UV light from sunlight (UV-A and UV-B) or to UV radiation (UV-C, e.g. halogen lights)

  • Consistently wearing clothing to cover the head, body, and eyes

  • Broad-spectrum sun protection with a high UV protection factor

  • Avoiding the consumption of tobacco

  • Training in self-examination to check for abnormal pigmentation changes

  • Treatment of pre-malignant lesions: cryotherapy

  • Larger areas: topical application of 5-fluorouracil, imiquimod preparations, with dermabrasion and dermatome shaving rarely necessary

  • Treatment of cutaneous neoplasia: curettage or excision

Surveillance Recommendations

Surveillance Recommendations

Evidence-based standards are lacking for early detection, particularly during childhood. The AACR consensus recommendations are listed for you as follows.

  • Hematology-oncology: following the diagnosis, avoidance of exposure to sunlight and ionizing radiation; early diagnosis and treatment of skin changes; screening for ocular neoplasia and tumors of the ENT area every 6-12 months

  • Dermatology: thorough skin examination every 3 months

  • Gastroenterology/nutrition: swallowing examination, need-based dietary supplementation

  • Ophthalmology: Medical examination every 6-12 months

  • Neurology: Testing for developmental retardation and progressive neurological changes

  • Orthopedics: annual scoliosis evaluation

  • ENT: basic audiogram (and as needed) and tumor screening every 6-12 months

Additional Information

Open Clinical Trials / Registries

There are currently no open clinical trials/registries for patients with Xeroderma Pigmentosum that we can recommend to you for more information.

Support Groups