Xeroderma pigmentosum
Xeroderma pigmentosum (XP) is a rare inherited genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation, leading to a significantly increased risk of developing skin cancers at a young age. This condition is caused by mutations in genes responsible for DNA repair, specifically those involved in nucleotide excision repair. There are several classes of xeroderma pigmentosum, each with varying severity and associated risks. Symptoms typically manifest in early childhood, including freckling, changes in skin pigmentation, and an increased propensity for skin cancer, particularly on the eyelids, which may also develop papillomas.
The prevalence of xeroderma pigmentosum varies globally, with about one in a million people affected in the United States and a higher incidence noted in certain populations, such as those in Japan and North Africa. Diagnosis is primarily based on clinical symptoms and family history, supplemented by genetic testing. Management strategies focus on rigorous UV protection measures, regular skin cancer screenings, and potential surgical interventions for malignancies. Emerging treatments, such as gene therapy, show promise in addressing the underlying genetic defects. Given its genetic nature, counseling is recommended for families with a history of xeroderma pigmentosum.
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Xeroderma pigmentosum
ALSO KNOWN AS: Xeroderma pigmentosa
RELATED CONDITIONS: Skin cancer, eyelid tumors, telangiectasia, photophobia, cognitive disabilities
DEFINITION: Xeroderma pigmentosum is an inherited genetic disease characterized by extreme sensitivity to ultraviolet (UV) radiation. Patients with this disease have an extremely high risk of developing skin cancer and often die from skin cancer at an early age. Different classes of xeroderma pigmentosum have greater or lesser risks due to the severity of their disease. Dark skin color does not protect xeroderma pigmentosum patients from skin cancer.
Risk factors: The main risk factor for xeroderma pigmentosum is having a family member with the disease.
Etiology and the disease process: Xeroderma pigmentosum is caused by the lack of functionality of genes responsible for DNA repair after damage caused by ultraviolet light. The disease is classified as XPA, XPB (ERCC3), XPC, XPD (ERCC2), XPE (DDB2), XPF (ERCC4), XPG (ERCC5), or ERCC1 depending on which of seven genes involved in nucleotide excision repair (DNA repair) are damaged. XP-variant (XPV, or POLH) is a class of xeroderma pigmentosum patients who have a mutated DNA polymerase eta gene. Xeroderma pigmentosum is an autosomal recessive genetic trait. The disease is staged as follows:
- Stage I: After six months of age, freckling, redness, and pigment changes appear on the skin.
- Stage II: Patches of light and dark skin (poikiloderma) and spider veins (telangiectasia) develop.
- Stage III: Malignant skin cancers develop, including eyelid tumors.
Incidence: In the United States, xeroderma pigmentosum affects one in one million people. In the Japanese population, the condition is more common, affecting about one in twenty-two thousand people. A higher prevalence has also been noted in North Africa and the Middle East.
Symptoms: Common symptoms in xeroderma pigmentosum are freckling, changes in skin pigmentation such as poikiloderma, dry skin (xerosis), and the eventual development of multiple malignant skin cancers. The eyelids may form papillomas or become atrophied, leading to deformity or the need for removal. Patients are sensitive to light, tend to suffer from conjunctival inflammation, and sunburn easily. Some patients exhibit immunosuppression and neurological problems such as learning disabilities, hearing loss, or degeneration of muscles and reflexes, especially in XPA and XPD. The intensity of symptoms varies by xeroderma pigmentosum class and exposure to ultraviolet light.
Screening and diagnosis: Clinical symptoms, often apparent within a year of birth, and family history are the first clues to xeroderma pigmentosum. Gene sequencing and other special tests are used to conclusively diagnose the disorder.
Treatment and therapy: Avoiding exposure to ultraviolet light, using sunscreen, and aggressive monitoring for skin cancer are necessary. Patients frequently require surgery or other treatment for skin cancer. Cases involving significant damage to eyelids may be treated with special eye drops or contact lenses to protect and moisturize the eyes. Gene therapy, which uses viral vectors to correct defects of XP, has shown promise in treating xeroderma pigmentosum. Topical treatments such as 5-fluorouracil and imiquimod have provided symptom relief.
Prognosis, prevention, and outcomes: Because xeroderma pigmentosum is an inherited genetic disease, genetic counseling is encouraged for those with a family history of the disorder before having children. Extreme measures are needed to protect the xeroderma pigmentosum patient from ultraviolet light from the sun or fluorescent lamps. Death from skin cancer is the typical outcome, usually by early adulthood.
Bibliography
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Hossain, Mozammel, et al. "Current Therapeutic Strategies of Xeroderma Pigmentosum." Indian Journal of Dermatology, vol. 66, no. 6, 2021, pp. 660-667, doi.org/10.4103/ijd.ijd‗329‗21. Accessed 17 June 2024.
Kraemer, Kenneth. “Xeroderma Pigmentosum - GeneReviews®.” NCBI, 20 June 2003, www.ncbi.nlm.nih.gov/books/NBK1397. Accessed 17 June 2024.
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“Xeroderma Pigmentosum.” MedlinePlus, 27 June 2023, medlineplus.gov/genetics/condition/xeroderma-pigmentosum. Accessed 17 June 2024.