Xeroderma Pigmentosum (Dry, Pigmented Skin) – A Rare Genetic Disorder of Skin!

A while ago I happened to come across an interesting science program on one of the medical channels while browsing through them on the television (idiot box as it is nicknamed). The topic being discussed was a rare genetic disorder known as Xeroderma Pigmentosum (XP) that affects about 1 in 250,000 people in the USA and is more common in North Africa, Japan and Middle East. I was very disturbed looking at children as young as 2 years old suffering from this condition. All of them had freckled, dry and pigmented skin. After watching the program, I decided to write an article about it which could be of help to many families who are having a member who has been affected by this disorder.

An eight year old girl from Guatemala with Xeroderma Pigmentosum. An eight year old girl from Guatemala with Xeroderma Pigmentosum. An eight year old girl from Guatemala with Xeroderma Pigmentosum.

What is Xeroderma Pigmentosum?

  • The condition was described for the very first time by Kaposi and Hebra in the year 1874. After observing the characteristic features, the disorder was named Xeroderma Pigmentosum, Xeroderma = dry skin, Pigmentosum = changes in skin coloring or pigmentation.
  • It is a rare genetic condition affecting the sun-exposed regions of the eyes and skin.
  • It is a hereditary condition inherited by the newborns from their parents in an autosomal recessive mode of inheritance. In this mode, for a child to get the disorder, both copies of the gene in each cell should have mutations i.e., both the parents (carriers) carry one copy each of the mutated gene and pass it on to their child, but they themselves do not exhibit any sympytoms associated with the condition.
  • Individuals with this condition are extremely sensitive to ultraviolet rays (UVA, UVB & UVC) of the sunlight.

What causes it?

All of us have heard about UV light present in the sunrays that hit the earth and the harm they cause to human body. One of the harms is the damage to the DNA or genetic material in the body. In normal conditions, the body can repair the damage and restore its normal functioning. The role of the repairing genes is to identify the site of DNA damage. This step is followed by the unwinding of the damaged regions of DNA, removing the abnormal sections and replacing the damaged DNA with normal and correct DNA.

But, in people with Xeroderma Pigmentosum, the damage caused to the DNA cannot be repaired, leading to the development of cancer or cell death in certain body parts. All the major characteristic features of this condition are a result of the piling up off the unrepaired DNA. When UV rays from sunlight cause damage to the genes responsible for controlling the growth and division of cells, the cells may either die or divide uncontrollably. Alterations in at least 8 genes are known to have a role in the disease development beginning from XP-A or complementation group A to XP-G or complementation group G and XP-V which is a variant type. Among these, more than half of the people in the USA develop this condition due to mutations in ERCC2, XPC and POLH genes.

Characteristic Features of Xeroderma Pigmentosum:

  • The signs and symptoms usually begin in infancy or early childhood.
  • The very first sign is severe sunburn soon after exposure to the sunlight just for a few minutes.
  • Blistering and redness of the affected skin that can last for several weeks.
  • Freckling of the skin on face, lips and arms is a sign in all the children affected by the time they reach the age of 2 years.
  • Visible Spider-like blood vessels below the skin.
  • Extreme discomfort when exposed to bright light, a condition known as photophobia.
  • Scaling and crusting of the skin.
  • Evident discolored skin patches in the affected and exposed areas.

Stages of the Disease:

The progression of this disease occurs in 3 stages.

Stage I – About 6 months after the birth of the child. Sun-exposed areas, especially face, shows reddening, freckling and scaling followed by the appearance of irregular dark spots (not in all cases). These physically evident changes may travel to the neck and lower areas of legs. All these skin changes may decrease during winters, when the sunlight is less.

Stage II – This is the second stage characterized by poikiloderma or irregular patches of darkened and lightened skin, thinning of the skin which enables the visibility of the spider web-like formation of blood vessels under the skin.

Stage III – By the time an affected child reaches the age of 9 or 10 years skin cancers and solar keratoses develop. Solar keratoses is the term used to describe rough scaly spots on the skin which appear as thickened or flat, warty or scaly, reddened or skin colored lesions.

Xeroderma Pigmentosum & Cancer:

People suffering from this condition are at a very high risk of developing skin cancer. Without any sun protection, nearly half of the children develop skin cancer by the age of 10. Moreover, people tend to develop multiple skin cancers during their lifetime. Lips, face, eyelids, scalp, eyes and tip of the tongue are the most viable areas for the development of cancers. Patients are at an increased risk of developing brain tumors and patients who smoke cigarettes are at a high risk of developing lung cancer. Incidence of cancer in patients below 20 years of age is 1000 times higher than the one seen in general population.

Xeroderma Pigmentosum & Eye Abnormalities:

Apart from a very high incidence of cancer, individuals with this condition are prone to severe eye abnormalities. Their eyes are extremely sensitive to UV rays. Unprotected eyes during exposure to sun may become irritated and bloodshot. Also, the cornea or the clear front covering of the eyes may become cloudy. Other abnormalities include falling out of eyelashes, thinning of eyelids and abnormal inward or outward turning of eyelids. Noncancerous growths on and in the eye and a high risk of eye cancer are seen among the patients. Vision may be impaired in most of the cases.

Xeroderma Pigmentosum & Neurological Complications:

Apart from the development and progression of cancers and eye abnormalities, nearly 30% of the patients develop progressive neurological complications. These include poor coordination, hearing impairment, loss of intellectual function, movement and difficulty walking, spasticity, short stature, delay in development, mental retardation, learning disabilities, seizures, and difficulty talking and swallowing. These neurological abnormalities tend to worsen as the individual ages.

Diagnosing the condition:

The disease is identified in early infancy, when the baby is around 1-2- years of age. The diagnosis usually begins with a complete physical examination and information on family history of the condition.

  • The very first clue in most of the children is the extreme sensitivity to sun exposure or even fluorescent lights in some cases.
  • XP may also be suspected in young children if they have a large number of freckles on their face.
  • Neurological and eye problems are another indication of the disease.

Before the birth of the baby, tests such as amniocentesis, culture of amniotic cells and chorionic villous sampling (removal of a small piece of chorionic villi, part of placenta from the uterus during early pregnancy) may help in the diagnosis of the condition.

After the birth of the child, skin biopsy and culture of skin fibroblasts help in confirming the diagnosis.

Can Xeroderma Pigmentosum Be Treated?

Unfortunately there is no cure for this condition. By now you might have understood the severe effects of sunlight on people suffering from this condition. Thus, the treatment options are aimed at protecting their skin from harmful UV rays. Patients need to take precautionary measures to avoid further progression of the disease.

Preventive Measures:

  • Protection at home – Proper window coverings, window tinting and using low wattage incandescent lights.
  • Always wear protective clothing which includes tightly woven fabrics that do not allow the light to pass through them, long sleeved and collared shirts, wide-brimmed hats, protective eye wear (very dark) specifically made to protect the eyes from UV rays while going outside, to avoid direct exposure to sunrays.
  • Avoid outdoor activities as much as you can and if it is mandatory limit your exposure time.
  • Make sure to cover the exposed areas of the body with a sunscreen whose SPF is 70 or more.
  • If possible restrict your outdoor activities to night time.
  • Make it a routine to get skin examinations done by an expert dermatologist who can recognize the signs of skin cancer immediately looking at the skin. Also, do not delay in reporting to your doctor of any suspicious skin growths or spots on the skin.
    • Every 3 to 6 months get an eye examination done by an expert ophthalmologist.
    • Testing on a yearly basis for potential neurological problems is suggested till the child enters his/her 20th year.


  • Patients who have had multiple skin cancers may be prescribed isotretinoin. This medication contains vitamin A derivative that may help in preventing the formation of new cancers.
  • Patients who have solar keratoses may be treated with 5-fluorouracil cream or cryotherapy.

What to Expect?

Most of the patients with Xeroderma Pigmentosum die of skin cancer in their early adulthood. But if diagnosed in early stages, the survival age may be increased by taking the above mentioned precautionary measures.

The condition cannot be prevented. Therefore, make sure to get a genetic counseling done if you have a family history of the disease and are planning to have babies.

Leave a reply

Your email address will not be published. Required fields are marked *