Alternative Names
XP
Symptoms & Characteristics
Xeroderma pigmentosum (XP) is a genetic condition in which the ability to repair DNA damage caused by ultraviolet (UV) light is deficient. This deficiency leads to the accumulation of irreversible DNA changes (mutations). Common characteristics include:
- Skin findings, which can often be seen as early as infancy. Skin findings may include severe sun sensitivity, severe sunburn and blistering even with minimal sun exposure, marked freckling and dark spots on sun-exposed areas, as well as dry and parchment-like skin.
- Eye problems are usually limited to the outside, sun-exposed portions of the eyes. Eye problems may include photophobia (severe sensitivity to light), conjunctivitis, pigmenting of the eyelids, inflammation (keratitis) and cloudiness of the corneas, turning out of the edge of the eyelid (called ectropion), as well as loss of eyelashes. The eyes are easily irritated and often become bloodshot.
- Nervous system abnormalities are present in about 30% of affected people. These neurological symptoms have a variable age of onset and may include acquired microcephaly (small head that develops after birth), poor coordination, seizures, muscle spasticity, progressive hearing loss, and progressive cognitive impairment.
Treatment
An important part of managing XP is avoiding sun and UV exposure. Cigarette smoking and exposure to other known carcinogens should also be avoided. Treatment depends on the specific symptoms; but early diagnosis, routine surveillance and treatment may help manage some of the symptoms.
How Common Is It?
About one in a million people are affected with XP in the United States.
XP is more common in certain geographic areas, including Japan, North Africa (Tunisia, Algeria, Morocco, Libya, and Egypt) and the Middle East (Turkey, Israel, and Syria).
Genetics & Inheritance
Xeroderma pigmentosum is caused by mutations in one of several different genes. XP is categorized into 9 groups called complementation groups each of which has an associated gene.
| Xeroderma Pigmentosum Genetics |
| Complementation Group |
Gene |
| A |
XPA* |
| B |
ERCC3 (XPB) |
| C |
XPC* |
| D |
ERCC2 (XPD) |
| E |
DDB2 (XPE) |
| F |
ERCC4 (XPF) |
| G |
ERCC5 (XPG) |
| H |
ERCC1 |
| Variant |
POLH (XP-V) |
| *Mutations in these two genes account for about 50% of all XP cases. |
We all have two copies of each of the above genes - one from each parent. In XP, it is necessary to have two mutations, one in each gene copy, to be affected. This is called autosomal recessive inheritance.
- Both parents of an affected person are obligate carriers (each have only one mutation). Two carriers have a 25% chance with each pregnancy to have an affected child, but typically do not have symptoms themselves.
There are other genetic conditions that have characteristics that overlap with XP. Some of these conditions include Cockayne syndrome, Rothmund-Thomson syndrome, and Baller-Gerold syndrome. A genetic consultation with a trained genetic professional is important for a complete evaluation, accurate diagnosis, as well as discussion of the benefits and limitations of testing and recurrence risk.
Genetic Testing
Before clinical genetic testing is possible, cells from an affected individual are assigned to a known complementation group using specialized research testing called host-cell reactivation (or other studies). Clinical genetic testing for the XPA and XPC genes that cause XP is available through an in person genetic consultation for people who are considered at risk. Research testing for the remaining genes may be available. Use our find a genetic professional directory to locate a trained genetic professional in your area.
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