Xeroderma pigmentosum
Xeroderma pigmentosum
Classification & external resources
| ICD-10 |
Q82.1 |
| ICD-9 |
757.33 |
| DiseasesDB |
14198 |
| eMedicine |
derm/462 neuro/399 |
| MeSH |
D014983 |
Xeroderma pigmentosum, or XP, is an autosomal recessive genetic disorder of DNA repair in which the body's normal ability to repair 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:
| Type |
Diseases Database |
OMIM |
Gene |
Locus |
Also known as/Description |
| Type A, I, XPA |
29877 |
278700 |
XPA |
9q22.3 |
Xeroderma pigmentosum group A. Classical form of XP. |
| Type B, II, XPB |
29878 |
133510 |
XPB |
2q21 |
Xeroderma pigmentosum group B. |
| Type C, III, XPC |
29879 |
278720 |
XPC |
3p25 |
Xeroderma pigmentosum group C. |
| Type D, IV, XPD |
29880 |
278730 278800 |
XPD ERCC6 |
19q13.2-q13.3 , 10q11 |
Xeroderma pigmentosum group D or De Sanctis-Cacchione syndrome. De Sanctis-Cacchione syndrome can be considered a subtype of XPD. |
| Type E, V, XPE |
29881 |
278740 |
DDB2 |
11p12-p11 |
Xeroderma pigmentosum group E. |
| Type F, VI, XPF |
29882 |
278760 |
ERCC4 |
16p13.3-p13.13 |
Xeroderma pigmentosum group F. |
| Type G, VII, XPG |
29883 |
278780 133530 |
RAD2 ERCC5 |
13q33 |
Xeroderma pigmentosum group G. |
| Type V, XPV |
|
278750 |
POLH |
6p21.1-p12 |
Xeroderma pigmentosum variant. 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. |
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.
NO
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]
References
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