xeroderma pigmentosum

Xeroderma pigmentosum has an autosomal recessive pattern of inheritance.

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.^[1]:574 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^[2]. XP is about six times more common in Japanese people^[2] 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.^[3] 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 ([1]) (though there are significant side-effects.) Existing keratoses can be treated using cryotherapy or fluorouracil.^[4]

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.

The condition is featured in the 1994 CBS Movie of the Week, Children of the Dark.

References

See also

• Biogerontology
• Cockayne syndrome
• Photophobia
• Senescence
• XPB

External links

Information

• An article about this disorder from DigiLander.iol.it (in English and Italian)
• DermNet systemic/xeroderma-pigmentosum

Charities

• XP Society
• XP Family Support Group
• UK Patient Support Group
• An article about an untreated XP patient with no access to modernized medical care, with photos.

Halpern, J.; Hopping, B.; Brostoff, J. (2008). "Photosensitivity, corneal scarring and developmental delay: Xeroderma Pigmentosum in a tropical country". Cases journal 1 (1): 254. doi:10.1186/1757-1626-1-254. PMID 18937855. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577106/. 

Short films

• Sloan Science and Film / Short Films / XP by David Barba 10 minutes
• Web Site of a Short Film about an Xeroderma pigmentosum (XP) Patient. Film is directed by Kimberly Williams Paisley