Xeroderma pigmentosum

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Xeroderma pigmentosum


Xeroderma pigmentosum is a rare inherited genetic disease. People with this condition develop skin and eye cancers at young ages because their DNA is extremely susceptible to damage caused by ultraviolet radiation. Xeroderma (dry, scaly skin) and pigmentosum (freckling and abnormal skin coloring) refer to changes that occur after exposure to sunlight or other ultraviolet radiation.


Xeroderma pigmentosum refers to a group of similar conditions. Each subgroup is designated by a letter or a roman numeral. Xeroderma pigmentosum is also often abbreviated XP. XP A and XP I are the same, as are XP B and XP II, XP C and XP III, etc. There are seven types of xeroderma pigmentosum designated A–G or I–VII. An eighth type of XP is called the "variant" type. XP VIII/XP H was once a separate subgroup; now it known to be part of XP D/XP IV.

Each of the eight types of xeroderma pigmentosum has its own DNA defect. However, each section of DNA affected is involved in the same process. These defects affect the body's ability to repair DNA damage, especially DNA damage to the skin caused by exposure to ultraviolet radiation. Sunlight is the most common source of ultraviolet radiation. Everyone's DNA is damaged when it is exposed to sunlight. However, the body has complex and very effective methods to repair the DNA damage. This repair mechanism does not work properly in people with xeroderma pigmentosum. They quickly accumulate damage to their DNA if they are exposed to ultraviolet radiation. Cumulative DNA damage leads to cancer , especially of the skin and the eyes.

DeSanctis-Cacchione syndrome refers to the combination of xeroderma pigmentosum along with mental retardation, short stature, and other symptoms. Trichothiodystrophy (TTD) is sometimes caused by the same DNA change that causes XP D, and rarely XP B. People with TTD also have brittle hair and nails, and physical and mental retardation.

Genetic profile

Xeroderma pigmentosum is inherited as an autosomal recessive condition. Everyone inherits one set of genetic material from each parent. People with xeroderma pigmentosum inherited one non-functional XP gene from each parent. Their parents have one normal gene and one abnormal gene (of that particular pair); they are called "carriers." Carriers do not have the autosomal recessive conditions because the normal gene in the pair protects them. Two carrier parents have a one in four chance with each pregnancy to have an affected child. A person with xeroderma pigmentosum will have an affected child only if the child's other parent is a carrier or is affected with XP.

The genetics of xeroderma pigmentosum are a bit complicated. The genetic defect in seven of the subgroups has been identified. Each subgroup (A–G) has its own abnormal gene. Each person with xeroderma pigmentosum has a particular subtype, which is associated with one specific abnormal gene. For example, a person with XP type A has no normal XP A gene but does not have XP type B and does not have the abnormal genes associated with XP type B. The genes for types A, B, C, D, E, F, and G are on chromosomes 9, 2, 3, 19, 11, 16, and 13. If two people with different forms of xeroderma pigmentosum had a child, the child would not have xeroderma pigmentosum. But if two people with the same type of xeroderma pigmentosum mated, all of their children would also have xeroderma pigmentosum.

This discussion involves two different types of DNA changes. The first DNA change is the change that the person with xeroderma pigmentosum inherits from both parents. This change (mutation) affects the repair enzymes and is present in every cell in his or her body. The second type of change discussed is additional DNA mutations that result from exposure to ultraviolet radiation. Since the skin and eyes are commonly exposed to ultraviolet radiation that damages DNA and since the body's repair system is not working, people with this condition have a high rate of mutation in the exposed organs. These mutations often manifest themselves as cancers—abnormal, uncontrolled growths. Thus, it is the combination of genetic defect and environmental exposure that causes the manifestations of this disease. The first DNA change would not be nearly as problematic if it did not predispose the person with it to accumulate many additional DNA mutations.


Xeroderma pigmentosum occurs in every ethnic group. It occurs equally in men and women. Approximately 1 in 250,000 people in the United States have xeroderma pigmentosum. The most common types are A, C, D, and the variant type.

Signs and symptoms

People with xeroderma pigmentosum have photo-sensitive skin. This means that their skin is hypersensitive to the effects of sunlight. Development of cancer at a young age is the most serious consequence. The eyes are also affected. Some people with xeroderma pigmentosum are affected intellectually, but not all. The symptoms a person will have are somewhat predictable based on which mutation he or she has.

Cutaneous symptoms

Skin manifestations usually begin in infancy. Early effects of skin exposure to minimal ultraviolet radiation include acute sunburn, blistering, freckles, increased or decreased pigment, birthmark-like spots, inflammation, dryness, and rough spots. The face, hands, neck, and arms are more severely affected because of increased sun exposure. Multiple scars may develop. The skin is normal at birth.

The average age at which people with xeroderma pigmentosum develop the first skin cancer is eight years. The risk to develop skin cancer is increased 1,000 times over the risk of the general population. A cell accumulates multiple abnormalities in its transition from a normal cell to a cancer cell. Cancers that occur frequently in people with xeroderma pigmentosum include squamous cell carcinoma, basal cell carcinoma, and malignant melanoma. Basal cell cancers are malignant and, if untreated, are characterized by relentless local invasion, but not metastasis elsewhere in the body. Squamous cell cancers are also malignant and, like basal cell carcinomas, tend to be local, although they are occasionally capable of metastasis. Malignant melanoma, as the name implies, is also malignant, but is much more agressive than either basal cell or squamous cell cancers of the skin. It is especially threatening because if not diagosed and treated early, it commonly will spread to internal organs and can be fatal. Cancer may occur on the eyes, lips, and tongue.

Ocular symptoms

Most people with xeroderma pigmentosum also have extremely light sensitive eyes. Their eyes easily become irritated, red, and swollen. Abnormal growths may appear. Cataracts may occur at an unusually young age.

Other symptoms

The other symptoms associated with xeroderma pigmentosum are variable. Many people who are affected have only eye and skin manifestations. Mental deterioration may occur; when it does, it usually worsens over time. Neurological symptoms are not believed to be associated with sun exposure. Some people have one or a combination of: deafness, poor reflexes, lower intelligence, or spasticity (in addition to ocular and cutaneous symptoms).


Xeroderma pigmentosum may be suspected based on a person's history of skin changes that occurred after minimal exposure to sunlight. The diagnosis is confirmed by a blood test or a skin test. The skin or blood cells are sent to a specialty laboratory. Studies are performed to determine whether the cells are hypersensitive to ultraviolet radiation. Scientists may examine whether abnormal changes can be seen in the chromosomes. The type of xeroderma pigmentosum may be determined by genetic studies or other specialized studies.

Genetic testing for xeroderma pigmentosum is complicated because there are eight different genes involved. Genetic tests are usually very specific, looking for a change in one gene. To confirm a diagnosis of xeroderma pigmentosum by DNA testing, scientists must look for multiple changes in eight different genes.

Prenatal diagnosis may be possible, especially if genetic studies have already been performed on an affected sibling and the parents.

Treatment and management

The only treatment for xeroderma pigmentosum is avoiding harmful exposure to ultraviolet radiation and treating/removing growths as they occur. The DNA damage caused by exposure to ultraviolet light accumulates over time and the resulting DNA damage is irreversible.

Life is changed dramatically when a family member has xeroderma pigmentosum. Extreme measures must be taken to completely avoid exposure to the sun. Preventative measures include: sunglasses, tightly woven long-sleeved clothing, wide brim hats, sunblock, and protective window coverings (at home, in the car, and at school). Children do not play outside during the day. All sources of ultraviolet radiation are avoided, even exposure to certain light bulbs. These precautions are critical to survival. Levels of ultraviolet radiation at home and at school can be measured with special instruments. Abnormal skin growths and other symptoms are treated/removed as they arise. Regular visits are made to the eye doctor, dermatologist, and neurologist. Often psychosocial support is also helpful.

Treatments that would deliver DNA repair proteins into the skin of affected patients are under investigation. Some people with xeroderma pigmentosum may be offered other types of medication, like isotretinoin. The dermatologist weighs the benefit of prescribing a medication against the side effects associated with that medication.

Because our bodies have different mechanisms for fixing different forms of DNA damage, people with xeroderma pigmentosum are most susceptible to DNA damage by ultraviolet radiation. Some other exposures have been associated with the type of DNA damage caused by ultraviolet radiation. Therefore, people with xeroderma pigmentosum should also avoid exposure to tobacco and certain other drugs.


Life expectancy is significantly reduced due to morbidity associated with the cancers. Researchers have not determined how effective preventative measures are, e.g. avoidance of ultraviolet radiation.

In the 1990s scientists discovered a great deal about DNA repair mechanisms, and about the genes associated with xeroderma pigmentosum. The range of symptoms associated with each type have been better defined. The media has also been interested in XP, giving it more attention than is typical for such a rare condition. Advocates in the XP community have developed helpful resources for other affected families, such as Camp Sundown. Hopefully the first decade of 2000 will also lead to new insights, services, and possibly new treatments.



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National Cancer Institute. Office of Communications, 31 Center Dr. MSC 2580, Bldg. 1 Room 10A16, Bethesda, MD 20892-2580. (800) 422-6237. <http://www.nci.nih.gov>.

Skin Cancer Foundation. 245 Fifth Ave., Suite 1403, New York, NY 10016. (800) 754-6490. [email protected]

Task Force on Xeroderma Pigmentosum, American Academy of Dermatology. Box 4014, Schaumburg, IL 60168-4014. (708) 330-0230.

Xeroderma Pigmentosum Registry. New Jersey Medical School, Dept. of Pathology, 185 South Orange Ave., Room C-520, Newark, NJ 07103-2714. (201) 982-4405.

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Michelle Queneau Bosworth, MS, CGC