Xeroderma pigmentosum, which is commonly known as XP, is an inherited condition characterized by an extreme sensitivity to ultraviolet rays from sunlight. This condition mostly affects the eyes and areas of skin exposed to the sun. Some affected individuals also have problems involving the nervous system. (Stefanini) The signs of xeroderma pigmentosum usually appear in infancy or early childhood. Many affected children develop severe sunburns after spending just a few minutes in the sun. The sunburn causes redness and blistering that can last for weeks. Saad) Other affected children do not get sunburned with minimal sun exposure, but instead tan normally. By age 2, almost all children with xeroderma pigmentosum develop freckling of the skin in sun-exposed areas. Such as the face, arms, and lips; this type of freckling rarely occurs in young children without the disorder. In affected individuals, exposure to sunlight often causes dry skin (xeroderma) and changes in skin coloring (pigmentation). This combination of features gives the condition its name, xeroderma pigmentosum. People with xeroderma pigmentosum have a greatly increased risk of developing skin cancer.
Without sun protection, about half of children with this condition develop their first skin cancer by age 10. (Lehmann) Most people with xeroderma pigmentosum develop multiple skin cancers during their lifetime. These cancers occur most often on the face, lips, and eyelids. Cancer can also develop on the scalp, in the eyes, and on the tip of the tongue. Studies suggest that people with xeroderma pigmentosum may also have an increased risk of other types of cancer, including brain tumors. Additionally, affected individuals who smoke cigarettes have a significantly increased risk of lung cancer. Janjua) The eyes of people with xeroderma pigmentosum may be painfully sensitive to UV rays from the sun. If the eyes are not protected from the sun, they may become bloodshot and irritated, and the clear front covering of the eyes (the cornea) may become cloudy. In some people, the eyelashes fall out and the eyelids may be thin and turn abnormally inward or outward. In addition to an increased risk of eye cancer, xeroderma pigmentosum is associated with noncancerous growths on the eye. Many of these eye abnormalities can impair vision.
About 30 percent of people with xeroderma pigmentosum develop progressive neurological abnormalities in addition to problems involving the skin and eyes. These abnormalities can include hearing loss, poor coordination, difficulty walking, movement problems, loss of intellectual function, difficulty swallowing and talking, and seizures. When these neurological problems occur, they tend to worsen with time. Researchers have identified at least eight inherited forms of xeroderma pigmentosum: complementation group A (XP-A) through complementation group G (XP-G) plus a variant type (XP-V).
The types are distinguished by their genetic cause. All of the types increase skin cancer risk, although some are more likely than others to be associated with neurological abnormalities. ( Janjua) Xeroderma pigmentosum is caused by mutations in genes that are involved in repairing damaged DNA. DNA can be damaged by UV rays from the sun and by toxic chemicals such as those found in cigarette smoke. Normal cells are usually able to fix DNA damage before it causes problems. However, in people with xeroderma pigmentosum, DNA damage is not repaired normally.
As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die. Many of the genes related to xeroderma pigmentosum are part of a DNA-repair process known as nucleotide excision repair (NER). The proteins produced from these genes play a variety of roles in this process. They recognize DNA damage, unwind regions of DNA where the damage has occurred, snip out the abnormal sections, and replace the damaged areas with the correct DNA. Inherited abnormalities in the NER-related genes prevent cells from carrying out one or more of these steps.
The POLH gene also plays a role in protecting cells from UV-induced DNA damage, although it is not involved in NER; mutations in this gene cause the variant type of xeroderma pigmentosum. (McGibbson) Gene therapy for xeroderma pigmentosum is still in a theoretical and experimental stage. Various methods of correcting the defects in xeroderma pigmentosum have been attempted in vitro and in animal studies using viral vectors (adenoviruses and retroviruses) carrying the gene replacement products. Ex: vivo skin gene therapy, which refers to grafting skin that has the genetic defect corrected, may be useful in xeroderma pigmentosum in the future. Oxford) The goal of treatment is to protect the patient from sunlight. To this end, regular visits to the dermatologist might be necessary for the purposes of patient education and early detection and treatment. (McGibbson) The use of sunscreens along with other sun-avoidance methods such as: protective clothing, hats, and eyewear can minimize UV-induced damage in patients with xeroderma pigmentosum. Sunscreens should be applied to all exposed surfaces including the hands, the back of the neck, the ears, the lower lips, and the anterior part of the chest.
Whenever UV exposure is expected this steps need to take action to limit and avoid exposure. The 2 basic types of sunscreens are physical and chemical. ( Task Force on Xeoderma) Oral retinoids have been shown to decrease the incidence of skin cancer in patients with xeroderma pigmentosum. This therapy is limited by dose-related irreversible calcification of ligaments and tendons. ( Diwan) Info Citations: Janjua, Shahbaz A. , MD. “Xeroderma Pigmentosa, Carcinoma, Squamous Cell – DermAtlas – Dermatology Image Atlas. ” Xeroderma Pigmentosa, Carcinoma, Squamous Cell – DermAtlas – Dermatology Image Atlas.
DermAtlas, 6 Oct. 2011. Web. 28 Feb. 2013. Lehmann, Alan R. , David McGibbon, and Miria Stefanini. “Multiple Reference Genomes and Transcriptomes for Arabidopsis Thaliana | ReadCube Articles. ” Multiple Reference Genomes and Transcriptomes for Arabidopsis Thaliana | ReadCube Articles. ReadCube Articles, 1 June 2011. Web. 28 Feb. 2013. http://emedicine. medscape. com/article/1119902-treatment Saad, Alaa. “Xeroderma Pigmentosum (2nd Stage). ” – DermRounds Dermatology Network. DermRounds, 17 Oct. 2010. Web. 28 Feb. 2013. http://www. dermrounds. com/photo/intradermal-nevus/next? context=latest Diwan, Hafeez A. MD, PhD. “Xeroderma PigmentosumA Treatment & Management. ” Xeroderma Pigmentosum Treatment & Management. Medscape, 29 Nov. 2011. Web. 28 Feb. 2013. Task Force on Xeroderma. “Understanding Xeroderma Pigmentosum. ” Clinical Center National Institutes of Health. N. p. , 2006. Web. 28 Feb. 2013. Media Citations: Lehmann, Alan R. , David McGibbon, and Miria Stefanini. “Multiple Reference Genomes and Transcriptomes for Arabidopsis Thaliana | ReadCube Articles. ” Multiple Reference Genomes and Transcriptomes for Arabidopsis Thaliana | ReadCube Articles. ReadCube Articles, 1 June 2011. Web. 28 Feb. 2013. ttp://emedicine. medscape. com/article/1119902-treatment Saad, Alaa. “Xeroderma Pigmentosum (2nd Stage). ” – DermRounds Dermatology Network. DermRounds, 17 Oct. 2010. Web. 28 Feb. 2013. http://www. dermrounds. com/photo/intradermal-nevus/next? context=latest Oxford. “Brain. ” Neurological Symptoms and Natural Course of Xeroderma Pigmentosum. Oxford Journals, 21 June 2008. Web. 28 Feb. 2013. http://brain. oxfordjournals. org/content/131/8/1979/F2. expansion. html “List Of Disease. ” List Of Disease. N. p. , 5 Oct. 2011. Web. 28 Feb. 2013. http://listofdisease. wordpress. com/2011/10/05/xeroderma-pigmentosum/