Xeroderma pigmentosum
From Wikipedia, the free encyclopedia
| ICD-10 | Q82.1 |
|---|---|
| ICD-9 | 757.33 |
| DiseasesDB | 14198 |
| eMedicine | derm/462 |
| MeSH | D014983 |
Xeroderma pigmentosum, or XP, is a 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.
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[edit] 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 pathway, using multiple enzymes which repair the UV-damage in healthy cells, is called nucleotide excision repair. The damage is excised by exonucleases, 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 less or no repair of UV-lesions.
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.
[edit] Types
There are 7 complementation groups, plus one variant form:
- Type A, I, XPA, Classical Form (Mendelian Inheritance in Man (OMIM) 278700)
- Type B, II, XPB (133510)
- Type C, III, XPC (278720)
- Type D, IV, XPD (278730)
- Type E, V, XPE (278740)
- Type F, VI, XPF (278760)
- Type G, VII, XPG (278780)
Patients with "XP-variant" (XPV) (278750), do not have mutations in NER genes and are proficient in damage repair. XPV patients suffer from mutation in a gene that codes for a specialized DNA polymerase called polymerase-η (eta). Polymerase-η can replicate over the damage and is needed when cells enter S-phase in the presence of a DNA-damage.
[edit] 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.
[edit] 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. ([2]).
[edit] 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 R. 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 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 movie and TV series "Midnight Sun" (タイヨウのうた, Taiyou No Uta, lit. "Song to the Sun") is about a 16-year old girl who has XP, and spends her time as a street musician at night.
- 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.
- 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.
