Rare Classroom: Xeroderma Pigmentosum

Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Xeroderma Pigmentosum

Sometimes called DeSanctis-Cacchione syndrome. 

What is Xeroderma Pigmentosum?

  • Xeroderma pigmentosum (XP) is a rare genetic disorder in which the ability of the body to repair DNA damage, such as that caused by ultraviolet light, is substantially reduced.
  • This disease causes serious damage to the skin along with a number of systemic symptoms and an increased risk of cancer, particularly skin cancer.
  • Symptoms are typically noticeable before the patient has reached one year of age.
  • Patients with the disease have been called “moon children” or “children of the night” due to their vulnerability to skin damage from the sun.
  • There is no cure for the disease and patients are forced to avoid sunlight exposure as much as possible.
  • There are eight different types of XP
  • Globally, the frequency rate of XP is 1 in 100,000.
    • The frequency rate varies greatly in different regions of the world; in India, frequency is much higher at 1 in 370 births. Meanwhile, in the UK, the frequency is only 1 in 1,000,000.

How Do You Get It?

  • This genetic disorder is inherited in an autosomal recessive pattern
  • In many cases, the nucleotide excision repair (NER) have been mutated
  • XP impacts the DNA repair mechanism in skin cells that normally counteracts UV light exposure
  • Mutations impacting at least eight genes have been identified as causing XP, but research suggests that there could be many more
    • These include the genes that code for XP repair proteins (XPA-XPG)
    • Others include ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, DDB2, POLH

What Are The Symptoms?

  • Symptoms of xeroderma pigmentosum include:
    • Severe sunburn after only minor sun exposure. This is often noticeable the first time that the child is exposed
    • Ulcers on the cornea
    • Development of heavy freckles in sun exposed areas early in life
    • Unusual dark spots on the skin
    • Solar keratoses – rough skin growths
    • Skin cancer
      • Patients have a 1,000 fold greater than average risk of skin cancer
    • Scaly skin
    • Eyes that are very sensitive to sunlight
      • May be cloudy, bloodshot, or otherwise irritated
    • Reduced hair growth on legs and chest
    • Skin blistering or freckling after very little sun exposure
    • Telangiectasia
    • Skin dryness
    • Loss of eyelashes and skin thinning around the eyes
  • Patients are also at an increased risk of brain and eye cancers
    • Around half of patients will have skin cancer by age ten without preventative measures
  • Neurological symptoms can occur in some patients. These can include:
    • Coordination problems
    • Seizures
    • Intellectual disability
    • Hearing loss
    • These symptoms are progressive, meaning that they tend to worsen over time

How Is It Treated?

  • There is no cure for XP
  • Available treatments are preventative or symptomatic in nature
  • The most important approach for controlling symptoms is to avoid sunlight exposure as much as possible. If the patient must be outdoors, they should wear protective clothing and sunscreen.
  • In severe cases, UV light from fluorescent lightbulbs, tobacco smoke, or even covered windows can be enough to trigger symptoms
  • Patients should be monitored closely for signs of cancer
  • Fluorouracil and cryotherapy are used to treat keratosis skin growths
  • Xeroderma pigmentosum patients have a much reduced life expectancy
    • The average life expectancy for patients is 37 years
    • For patients with neurological symptoms, life expectancy is only 29 years
    • Patients that are never exposed to sunlight can survive longer

Where Can I Learn More???

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