Xeroderma Pigmentosum

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What is Xeroderma Pigmentosum?

Xeroderma pigmentosum (XP) is an extremely rare inherited condition affecting the skin and eyes. It is also referred to as DeSanctis-Cacchione syndrome.

According to a quote, "People with xeroderma pigmentosum experience an almost 100% risk of developing multiple skin cancers if their environment is not very carefully controlled."

Xeroderma pigmentosum (XP) was first described by Hebra and Kaposi in 1874. The term “xeroderma pigmentosum” for the condition was coined by Kaposi in 1882, referring to its characteristic dry and pigmented skin.

XP is characterized by marked sensitivity to sunlight (ultraviolet radiation) and an inherited inability of the body to repair the damage caused by ultraviolet radiation from the sun. Unless precautions are taken to protect from sunlight, there is severe damage to the skin and eyes and resultantly increased occurrence of skin and eye cancers.

It is therefore a precancerous condition. Nearly 25 percent of affected persons also have central nervous system (CNS) involvement for reasons not clear.

How is Xeroderma Pigmentosum Caused?

Xeroderma pigmentosum occurs when the genes involved in the repair of DNA (deoxyribonucleic acid, the genetic material) in the cell are faulty.

Normally when a person is exposed to ultraviolet radiation or toxic chemicals, for example, cigarette smoke, the DNA damage caused is corrected by innate repair mechanisms in cell repair before it can cause any serious problems. However in XP, the body is unable to repair this DNA damage and as more and more DNA abnormalities accumulate, the cell may either become cancerous or die.

How does a Person Inherit Xeroderma Pigmentosum?

Xeroderma pigmentosum is an inherited autosomal recessive condition. This means that the person carries two copies of a faulty gene (one from each parent), with consequent disruption of normal cellular repair mechanisms of the body when exposed to ultraviolet radiation (from sun exposure).

Although both parents also carry one copy each of the faulty gene, they are not affected because two copies of the faulty gene are necessary for the condition to get manifested clinically by the definition of an autosomal recessive condition.

Xeroderma pigmentosum affects both sexes and all ethnic groups. Estimated rates of incidence vary from 1 in 250, 000 in the USA, approximately 2.3 per million live births in Western Europe and Japan (1 in 20,000). It is more prevalent particularly in the Middle East and North Africa, probably due to the high degree of consanguinity in these regions.

What are the Genetic Changes in Xeroderma Pigmentosum?

Inherited changes (mutations) in at least eight genes have been found to cause Xeroderma pigmentosum. The normal variants of these genes are involved in various DNA repair mechanisms within the cell that are referred to as nucleotide excision repair (NER).

The genes involved in DNA repair (NER) perform the following important functions:
  • Recognize that DNA damage has occurred
  • Unwind portions of DNA where the damage has occurred
  • Cut out (excise) the abnormal areas, and
  • Replace the damaged portions with the normal DNA.
Thus, inherited defects in the NER-related genes (7 genes) prevent cells from carrying out one or more of these steps. Additionally, the POLH gene is another gene that is involved in protecting cells from UV-induced DNA damage, although it is not involved in the steps of NER. Mutations in the latter gene (POLH) lead to a type of XP referred to as the “variant” form (XP-V), while the remaining seven types are known as groups A, B, C, D, E, F, and G.

What are the Symptoms and Signs of Xeroderma Pigmentosum?

The major clinical features of xeroderma pigmentosum occur due to a buildup of abnormal unrepaired DNA. When abnormal DNA builds up, cells can either die or multiply in an unregulated manner. Such uncontrolled cell growth can lead to the development of cancerous tumors. Although the brain is not exposed to UV rays, neurological abnormalities are also thought to result from an accumulation of DNA damage; it is suspected that other factors contribute to DNA damage in nerve cells. However, it is unclear why some people with xeroderma pigmentosum develop neurological abnormalities while many do not.

Signs & Symptoms of Xeroderma Pigmentosum

The various clinical features of Xeroderma pigmentosum affecting the skin, eyes and nervous system include:
  • Tendency to sun burn easily despite adequate sun protection, unrelated to the color of your skin. Persons with XP-V do not have neurological problems and their sunburn pattern conforms to their skin type
  • Unusually long time (few weeks) for the sunburn to resolve
  • Freckles from an early age (under two years) at sites exposed to daylight
  • Marked eye sensitivity to bright light (photophobia), becoming clouded or bloodshot
  • Increased incidence of skin cancers - Without adequate protection, nearly half the children with this condition develop skin cancer by 10 years. Sites involved are face, lips, eyelids and scalp
  • Noncancerous and cancerous tumors of the eye
  • Premature skin aging (skin of affected persons resembles the skin of elderly persons who have spent much of the time under the sun)
  • Nerve/brain (neurological) problems, such as hearing loss, poor memory or learning problems and poor balance
  • Short stature
  • Lack of development of normal sexual characteristics in some cases
In persons with XP, the changes caused by sun exposure and damage usually begin in infancy, and almost always before 20 years of age.

What are the Risks Factors of Xeroderma Pigmentosum?

Xeroderma pigmentosum is an inherited condition. Therefore, the risk factors of this condition include:
  • Having a parent or both parents who are carriers of the defective gene or have the disease
  • Certain regions such as Middle East and North Africa where marriage between blood relatives and first cousins is common

How do you Diagnose Xeroderma Pigmentosum?

Clinical history and physical examination

In most cases, the initial clinical diagnosis can be made on the basis of extreme sensitivity to sun exposure, or by the appearance of freckles on the face at an unusually early age. A history of consanguinity between the parents may be an additional clue.

Confirmatory Tests for Xeroderma Pigmentosum

Tests to detect defective DNA repair

When there is a high index of suspicion, a piece of skin is removed (skin biopsy) using a local anesthetic and sent for a confirmatory test. These tests detect defective DNA repair and are offered in several countries.

Skin Biopsy Can Helps to Detect Defective DNA Repair

A type of cells found in the skin termed fibroblasts that are hypersensitive when exposed to UV radiation can be studied with the help of a microscope to see how effective the DNA repair mechanism is. A blood sample can also be used to perform this test.


A skin biopsy may show findings of hyperkeratosis and increased pigmentation along with other findings which may confirm the diagnosis.

Genetic Testing

Molecular testing and gene sequencing can be done to identify the specific defect.

Prenatal diagnosis

Prenatal diagnosis may be done if there is already an affected sibling or one of the parents is affected by the condition. The DNA repair tests can be performed on amniotic cells or chorionic villi derived cells. Molecular analysis can also be done in the presence of a known mutation.

How is Xeroderma Pigmentosum Managed?

Xeroderma pigmentosum is a chronic lifelong condition with no cure. It can be controlled effectively by the following measures:

Tips to Prevent & Manage Xeroderma Pigmentosum
  • Complete protection from ultraviolet light to reduce skin damage to a minimum possible level. Exposed skin should be covered with sunscreen and lip balm should be applied. Long sleeved dresses and full length dresses are preferable
  • UV resistant face mask can be worn but if this is not preferred, a broad-brimmed hat along with wraparound sun glasses must be worn
  • Areas of bright light should be avoided or Take simple preventive measures to adequately protect yourself
  • Periodic skin checks (usually three monthly) to identify and treat any signs of skin cancers early
  • Eye check (at least once a year) to detect any lesions as early as possible and to ensure you are offered treatments, advice about glasses and biopsies of any suspicious parts in the eye
  • Neurological assessment to identify any associated brain or nerve problems. This involves a thorough physical examination and sometimes hearing tests, nerve conduction studies and an MRI scan

    Neurological problems may be appropriately managed with hearing aids, speech therapy, physical therapy and occupational therapy
  • Addressing psychological issues through counseling and support; many children feel isolated by peers both at home and school. Job prospects may be limited
  • Regular blood tests to check vitamin D levels so that supplements can be given if required. This is because people with XP have a low vitamin D level as a result of rigorous measures to protect them from the sun
  • Avoid exposure to cigarette smoke as this is associated with an increased risk of lung cancer, and other harmful potentially cancerous environmental chemicals

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