Xeroderma pigmentosum


What is Xeroderma Pigmentosum?

Xeroderma pigmentosum (XP) is an inherited autosomal recessive disease that is characterized by photosensitivity, pigmentary changes, premature skin aging, and malignant tumour development.6 These manifestations are due to a cellular hypersensitivity to ultraviolet (UV) radiation caused by a defect in DNA repair, which leads to an increase of 1000-2500 times the risk of cancer. These symptoms appear before patients have 2 years old and they have an increased risk of developing skin cancer before 10 years old between 1.000 and 2.500 times more. Damage by ultraviolet rays in the eyes can lead to loss of vision and eye cancer. Estimated incidences vary from 1 in 20,000 in Japan to 1 in 300,000 in the USA6, and approximately 2.3 per million live births in Western Europe7.

Autosomal recessive inheritance
Autosomal recessive inheritance scheme. Wikipedia

XP  an is an inherited rare disease passed down from parents to children in an autosomic recessive manner, meaning that the person needs to receive both alleles of the mutation of this gene to suffer from the illness8. This disease is caused by mutations in the group of genes of Xeroderma Pigmentosum that are involved in repairing damaged DNA in our skin cells. This is essential as a protection mechanism against the mutations caused by UV light in our skin cells.

Ultraviolet light reacts with our genes, causing mutations in our DNA. UV is present during all daylight hours, through windows, found in many types of artificial lighting and even lightning or cloudy days. Normal cells are usually able to fix DNA damage before it causes problems. However, in people with XP, DNA damage is not repaired normally in the cells of their. As more abnormalities occur in the DNA of these cells, mutations accumulate and may cause a normal cell to turn into a cancer cell.

Ultraviolet affects mostly in the highest exposed areas of the body: skin and eyes. Interestingly, UV comes from the sun but also from some artificial lights such as fluorescents and halogens. Other tumours have been described in these patients because of its inability to repair DNA damage for example in brain, lung, thyroids, breast, kidney, testis and prostate or leukaemia. This risk comprehends a 10-20 times higher than in regular population.

There is no cure for XP, but much can be done to prevent and treat some of the problems it causes. Protection from all sources of UV is required, including total daylight avoidance via specialized clothing, sunscreens and sunglasses, even during short periods of exposition or cloudy days. It is recommended to measure the UV radiation at any change of illumination with an UV meter to avoid exposition to UV levels above 1uW/cm2. Protection with UV filters should be done in windows at home, school, work place, as well as in the car. A significant commitment to lifestyle changes is also required to reduce against the risk of exposure and combat its effects.

Other symptoms than hyperpigmentation and burns in sun exposed areas can appear such as photo-aged skin too early or thin skin or progressive neurological complications in some types of XP including hearing loss or progressing to deafness, developmental disabilities and mental retardation. People with XP must also undergo frequent skin, eye and neurological examinations, as approximately 30%  of XP patients will develop neurodegeneration9, and have prompt removal of cancerous tissue. For more details on prevention and therapies, please refer to section Treatments.

6Zghal, M., Fazaa, B., Abdelhak, S. & Mokni, M. Xeroderma pigmentosum. Ann. Dermatol. Venereol. 145, 706–722 (2018).
7Lehmann, A. R., McGibbon, D. & Stefanini, M. Xeroderma pigmentosum. Orphanet J. Rare Dis. 6, 70 (2011).
8Kraemer, K. H., Lee, M. M. & Scotto, J. Xeroderma Pigmentosum. Arch. Dermatol. 123, 241 (1987).
9Griffiths, C. (Christopher), Barker, J., Bleiker, T., Chalmers, R. (Robert J. G. . & Creamer, D. Rook’s textbook of dermatology. (2016).
Last modified
21 October 2019