Causes and Risk Factors of Xeroderma Pigmentosum

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Xeroderma pigmentosum (XP) is a rare genetic condition that runs in families and is passed from both parents to their child. Those with XP must keep away from ultraviolet light (UV) like that from the sun. Starting when they are very young, if they get even a little sun for a short amount of time, their skin burns and blisters.

Those with this condition are particularly prone to skin cancer, as well as often to developing eye and neurological problems. This article will discuss the causes of xeroderma pigmentosum, the role of genetics, and lifestyle risk factors.

gene mutation

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Common Causes

Xeroderma pigmentosum is a hereditary condition for which both parents contribute a copy of the flawed gene to their child. It is what's known as an autosomal recessive disorder.

The good news is that this is a very rare genetic mutation with unlikely odds of occurring. But, however slight the likelihood, children do inherit this condition from time to time.

Genetics

XP is what's known in genetic terms as an autosomal recessive disorder. The condition can occur only when both genetic parents pass down a flawed copy of the gene.

If only one copy is passed down, the child does not show signs of the condition, but rather is what's known as a carrier. Any carrier of the XP gene has a risk of having a child with the condition.

If two XP carriers have a child, the chances of that child having that condition are 25%. But the chances of having a child who's a carrier in this situation is 50%.

While it's highly unlikely to find a random person who also carries this recessive gene, the odds go up if both people are related. Related carriers are known as consanguineous.

For example, if you share a set of great-great grandparents, one of whom passed down a copy of the XP gene, you are far more likely to both be carriers. Both males and females have about the same chance of being a carrier as the mutation is on one of the chromosomes that do not determine sex.

Out in the world, XP carriers tend to be extremely rare. They are more common in some regions than in others. In the United States or in Europe, the prevalence of XP is only about 1 in 1 million. But in Japan, the prevalence is much higher, with 1 out of every 22,000 people affected by XP.

However, this is not just about one flawed gene. There are actually nine different genes that are capable of causing XP. They are:

  • DDB2 (XP-E)
  • ERCC1
  • ERCC2 (XP-D)
  • ERCC3 (XP-G)
  • ERCC4 (XP-F)
  • ERCC5 (XP-B)
  • POLH (XP-V)
  • XPA
  • XPC

These genes are all responsible for DNA repair. Eight of them are part of what's known as the nucleotide excision repair pathway (NER). As for the ninth, this mutation works to bypass unrepaired damage.

If someone inherits two flawed copies of any one of these genes, when DNA damage occurs it will not be detected and this damage will not be able to be properly repaired as it normally would be. This person will then begin showing signs of the disorder.

Lifestyle Risk Factors

With XP, damage to DNA such as can be produced by exposure to UV radiation is not properly repaired, so the person must avoid exposure to UV light. Prevention becomes the watchword.

About half of the people in the world with these mutations have a defect in the XPC gene. People with this mutation have issues with sun sensitivity. They must cover up with long sleeves and long pants and rely on high-SPF sunscreen.

Those with this particular mutation have no neurological abnormalities and experience normal growth and development.

Cigarette smoke contains certain carcinogens that can damage DNA. Since this can't be repaired in individuals with XP, it's important to prevent the damage by avoiding smoking, as well as any secondhand smoke. Those patients who do smoke go on to develop lung cancers.

Summary

Xeroderma pigmentosum is an inherited condition that leaves people vulnerable to DNA damage, particularly from UV light. Those with this condition have an extreme sensitivity to the sun and are prone to developing skin cancer and other cancers.

Fortunately, this condition is a very rare one in which two copies of a mutated gene, one from each parent, are needed for a case to occur.

A Word From Verywell

Whether you or someone in your family has xeroderma pigmentosum or is a carrier for this condition, understanding more about the causes can be helpful. Anyone who is a carrier may find it reassuring to better understand the genetics here and see what this means for any family planning.

People with the condition can benefit from understanding just what's happening at the cellular level. Hopefully, in the future, gene repair will make treatment for this condition possible.

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3 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Mount Sinai. Xeroderma pigmentosum.

  2. National Organization for Rare Disorders. Xeroderma pigmentosum.

  3. Sarasin A, Munier P, Cartault F. How history and geography may explain the distribution in the Comorian archipelago of a novel mutation in DNA repair-deficient xeroderma pigmentosum patientsGenet Mol Biol. 2020;43(1 suppl 1):e20190046.