xeroderma pigmentosum

Xeroderma pigmentosum, or XP, is an autosomal recessive genetic disorder of DNA repair in which the body's normal ability to remove damage caused by ultraviolet (UV) light is deficient. This leads to multiple basaliomas and other skin malignancies at a young age. In severe cases, it is necessary to avoid sunlight completely.

Causes

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 6-4PP (pyrimidine-6-4-pyrimidone photoproducts). The normal repair process is called nucleotide excision repair. The damage is excised by endonucleases, then the gap is filled by a DNA polymerase and sealed by a ligase. The most common defect in xeroderma pigmentosum is a 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. If mutations affect important genes, like tumour suppressor genes (e.g. p53) or proto oncogenes then this may lead to cancer. Since in XP patients the frequencies of mutations is much elevated, these patients have a predisposition for cancer.

Types

There are 7 complementation groups, plus one variant form:

Symptoms

Some of the most common symptoms of XP are:

• 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.

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.^[1]

In popular culture

• A notable fictional character who suffers from XP is Christopher Snow featured in the novels Fear Nothing and Seize the Night by Dean Koontz.
• The Lifetime Network movie Children of the Dark (1994) is about two young girls who have been diagnosed with an extreme case of XP and how their family copes with it.
• Lurlene McDaniel's "Night Vision" tells the story of a lonely girl with extreme XP and a young man who befriends her.
• The television miniseries Ultraviolet includes a character, Oliver, who has XP.
• In the television series Forever Knight, the main character is a vampire who explains his aversion to sunlight by claiming he has XP.
• In the 2001 film The Others, the two main child characters have XP.
• During the second season of ABC's Extreme Makeover: Home Edition, the Pope family was selected for an Extreme Makeover as their daughter, Shelby, suffers from XP. Later, ABC and the Popes teamed with Walt Disney World to give XP children a special treat – Walt Disney World made a special night-time opening (midnight to 4 AM) so XP children could spend time at the popular park. Footage from this event aired as part of an Extreme Makeover holiday special on December 11, 2005.
• The 2006 Japanese TV series Taiyou no uta is about an 16-year-old girl named Kaoru, who has XP. Kaoru has a talent for singing and songwriting with a guitar, but XP starts to ravage her guitar playing, by which her friend Koji began to accompany her on guitar instead, and soon, other friends joined in to form a band they called Moon Child.
• The Girl who Lives in the Dark (2006) documents the story of Wan Lao Yang. Wan Lao Yang is a 9-year-old girl from China suffering from XP. This film documents Wan Lao’s journey to Shanghai, and the treatment she receives from a specialist from the famous Great Ormornd Street Hospital. It also explores the work of NASA’s Sun Protection Team which has created a customised ‘sun suit’ for Wan Lao that blocks out 100% of U.V. light.
• In the anime Ouran High School Host Club, the occult-obsessed character Umehito Nekozawa seems to suffer from XP, but whether it is clinical or that he simply does not like the light remains unknown.
• In the video game Ace Combat 3, Rena Hirose suffers from the fictional "Silver Stone Disease", which has similar (if not the same) symptoms as XP.
• In the novel "A Cool Moonlight" by Angela Johnson, the main character Lila suffers from XP.

See also

• Biogerontology
• Cockayne syndrome
• Photophobia
• Senescence
• XPB

References

1. ^ DermNet systemic/xeroderma-pigmentosum

External links

• XP Society
• XP Family Support Group
• UK Patient Support Group
• An article about this disorder in English and Italian
• Web Site of a Short Film about an Xeroderma pigmentosum (XP) Patient. Film is directed by Kimberly Williams Paisley
• Article About the Xeroderma pigmentosum (XP) Society by William Lambers (pdf format)

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