Xeroderma pigmentosum

Xeroderma pigmentosa, or XP, is an autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet (UV) light is deficient. This disorder leads to multiple basal cell carcinomas (basaliomas) and other skin malignancies at a young age. In severe cases, it is necessary to avoid sunlight completely. The two most common causes of death for XP victims are metastatic malignant melanoma and squamous cell carcinoma. XP is about six times more common in Japanese people than in other groups.

The most common defect in xeroderma pigmentosum is an autosomal recessive genetic defect whereby nucleotide excision repair (NER) enzymes are mutated, leading to a reduction in or elimination of NER. Unrepaired damage can lead to mutations, altering the information of the DNA in individual cells. If mutations affect important genes, such as tumour suppressor genes (e.g. p53) or proto oncogenes, then this disorder may lead to cancer. Patients exhibit elevated risk of developing cancer, such as basal cell carcinoma.

Normally, damage to DNA in epidermal cells occurs during exposure to UV light. The absorption of the high energy light leads to the formation of pyrimidine dimers, namely CPDs (cyclobutane-pyrimidine-dimers) and 6-4PPs (pyrimidine-6-4-pyrimidone photoproducts). The normal repair process entails nucleotide excision. The damage is excised by endonucleases, then the gap is filled by a DNA polymerase and "sealed" by a ligase.

Types

There are 7 complementation groups, plus one variant form :

Symptoms

Some of the most common symptoms of XP include:

An unusually severe sunburn after a short sun exposure. The sunburn may last for several weeks. The sunburn usually occurs during a child's first sun exposure.
Development of many freckles at an early age
Irregular dark spots on the skin
Thin skin
Excessive dryness of skin
Rough-surfaced growths (solar keratoses), and skin cancers
Eyes that are painfully sensitive to the sun and may easily become irritated, bloodshot, and clouded
Blistering or freckling on minimum sun exposure
Premature aging of skin, lips, eyes, mouth and tongue
Crusting skin
Spidery blood vessels
Scaly skin
Oozing raw skin surface
Limited growth of hair on chest and legs

Treatment

The most important part of managing the condition is reducing exposure to the sun. The number of keratoses can be reduced with Isotretinoin ([http://www.emedicine.com/DERM/topic462.htm#section~treatment]) (though there are significant side-effects.) Existing keratoses can be treated using cryotherapy or fluorouracil.

Prognosis

Fewer than 40% of individuals with the disease survive beyond age 20 years. Individuals with milder disease may survive beyond middle age.

In popular culture

Fictional characters with severe cases of XP sometimes play prominent roles in books and movies. Some of the most notable characters include Christopher Snow, the protagonist and narrator of Dean Koontz' Moonlight Bay Trilogy of novels, and the children of the protagonist of Alejandro Amenábar's 2001 film, The Others. In Taiyou no Uta, a Japanese movie and TV drama of the same name, the protagonist Amane Kaoru has Type A XP. Also featured in the 1994 CBS Movie of the Week, Children of the Dark.

Translation

The phrase "Xeroderma pigmentosum" occurs as such in the following languages: English, Danish, German, French, Indonesian, Dutch.

Translation(s) in other languages: Bulgarian: Ксеродерма, Catalan: Xerodèrmia pigmentada, Spanish: Xerodermia pigmentosa, Italian: Xeroderma pigmentoso, Hebrew: קסרודרמה פיגמנטוזום, Japanese: 色素性乾皮症, Polish: Skóra pergaminowa, Portuguese: Xerodermia pigmentosa, Russian: Ксеродерма, Serbian: Ксеродерма пигментозум, Chinese: 著色性乾皮症.