Xeroderma Pigmentosum Health Article

Definition

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.

Description

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 nonfunctional 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 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.

Demographics

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