What Is Xeroderma Pigmentosum?

Xeroderma Pigmentosum is a rare genetically acquired condition that increases a person's sensitivity to UV radiation in the sunlight and causes skin cancers and eye and neurological problems quite early in life. The condition has no cure, but it can be managed with strict protection from sunlight and regular health checkups.

Xeroderma pigmentosum is characterised by sensitivity to UV radiation (UVR) in sunlight, leading to dry, freckled skin and skin cancers early in life, together with eye and neurological issues. The cause is a defect in the DNA repair genes, which are supposed to protect the skin from UVR  damage. This defect makes the skin more susceptible to the harmful effects of UV radiation on the skin. Hence, this dramatically increases the risk of skin cancers in the individual.

It is a genetically acquired disease which is transmitted to a child when both parents are carriers of this defective gene. 

It can be suspected that first sun exposure causes extensive skin changes in a baby.

What are the signs and symptoms of xeroderma pigmentosum?

• Severe sunburns at first exposure - Babies or small children who are first exposed to sunlight may get severely sunburnt.² The sunburn would also appear to persist for more than 10 days.³ It can be seen to happen on overcast or cloudy days.
• Freckled, pigmented skin - These occurring with sun exposure, irrespective of the skin colour, is another clue to the diagnosis
• Red eyes -Some children get sore or red eyes on exposure to daylight³ 
• Skin ageing - Early onset skin ageing, as well as severely dry skin, is another feature.

What causes xeroderma pigmentosum?

In this condition, there is a defect in the gene responsible for repairing DNA damage caused by UV light exposure. This leads to extensive damage to the skin without the ability to repair it. 

This is a genetically acquired condition which is seen to be autosomal recessive in its pattern of transmission.

In such cases, both parents need to be carriers of this genetic trait to pass it on to the offspring. In other words, a child needs to get two defective genes from the parents to have the condition.

Who is at risk of getting xeroderma pigmentosum?

Children of consanguineous parents (parents who are also first cousins) have an increased risk of getting this condition.⁴ This is because the carriers do not manifest the disease, and hence, it will be undetected in parents prior to the birth of the child.  Also, the chances of both parents carrying a similar gene are higher due to consanguinity. 

Also, if there is a family history or, in other words, if a person in the family already has this condition, there is an increased risk of developing this condition.

Additionally, it is reported that having Japanese ancestry also poses a higher risk than other populations, although the reason is not known.⁴

How common is xeroderma pigmentosum?

This condition is rare. It is said to be detected in about 1in 250,000 people in the US, and the same figure is true for Europe as well.¹ Countries like Japan have a slightly higher incidence of the disease.

How can xeroderma pigmentosum be diagnosed?

A doctor would take a detailed clinical history of the symptoms concerning sun exposure and do a physical examination.

Sometimes, a skin biopsy, meaning a small sample of skin, is taken to test for features of this disease. ⁵

The definitive diagnosis is based on a genetic test that will show the defective gene pattern.

Can I know if my baby is going to have this condition before the baby is born( while in utero)?

It is possible to diagnose Xeroderma Pigmentosum antenatally while the baby is still in the womb. A procedure called amniocentesis or chorionic villi sampling is needed to diagnose this. Both these are invasive procedures are performed whilst the mother is pregnant, with some risks. These procedures sample some cells shed from the baby or placenta and check for the genetic defect.

What are the skin cancers that can occur with xeroderma pigmentosum?

These cancers include squamous cell carcinoma, basal cell carcinoma and melanoma. The cancers also tend to be multi-focal and occur early on. However, with good protection from UV light early on, these can be minimised.

What is the risk of having skin cancer when having xeroderma pigmentosum?

Having Xeroderma Pigmentosum increases a person’s skin cancer risks by many thousandfold. Therefore, once diagnosed, the mainstay of management is prevention by protecting the skin from exposure to UV light.

What are the eye conditions that can develop when a person has xeroderma pigmentosum?

There is a generalised sensitivity of the eyes to daylight. Additionally, complications in the cornea, like keratitis, which means inflammatory changes, as well as ulceration and pterygium, which is a small growth on the eye, can occur.⁵ In some cases, eye surface cancers can also develop, which include basal cell carcinoma, squamous cell carcinoma and melanoma.

What are the neurological problems that can develop when a person has xeroderma pigmentosum?

About 25 to 30%of people are reported to develop neurological issues. Some people tend to develop hearing loss of both sensory and neural types. 

Some people can develop cognitive impairment, especially quite early on in life. 

Later on symptoms can occur in the cerebellum, which is the posterior part of the brain. These include problems in articulation called dysarthria as well as balance problems, difficulty in walking etc.⁵

How can xeroderma pigmentosum be treated?

Treatment and management of Xeroderma Pigmentosum (XP) primarily revolve around minimising exposure to ultraviolet (UV) radiation from the sun and other sources. Sun protection is crucial for individuals with XP since their skin cannot properly repair UV-induced DNA damage. This often involves wearing protective clothing, such as wide-brimmed hats, long-sleeved shirts, and sunglasses with UV protection, and using a broad-spectrum sunscreen with a high SPF rating and reapplying it frequently. Additionally, home and vehicle windows may be equipped with UV-blocking films to reduce indoor UV exposure. Individuals with XP are also advised to limit outdoor activities during peak sunlight hours. 

Regular skin examinations by dermatologists are essential to detect and treat any skin abnormalities or early signs of skin cancer. For those who do develop skin cancer, various treatment options are available, including surgery, chemotherapy, and radiation therapy. Moreover, ongoing research explores potential gene therapies and medications that may improve the DNA repair mechanisms in XP patients. 

In summary, managing XP involves a combination of strict sun protection measures, vigilant medical monitoring, and ongoing research into potential treatments to enhance the quality of life for those affected by this rare genetic disorder.

How to avoid or minimise exposure to UVR in day-to-day life?

• UVR is highest when the sun is directly overhead between 11 am and 3 pm, and it’s best to avoid outdoor activity in this period.⁶
• Note that UVR can be present even when it is rainy or cloudy during the daytime, but it is not present at night.
• Wear covering clothes with thick material or multiple layers, which tend to block UVR, and note that dark colours tend to absorb UVR.

How frequently should check-ups be performed for complications of xeroderma pigmentosum?

Some reports recommend a skin check-up every 3 months, an eye check-up annually, and neurological assessments are performed every 6 months if having a neurological issue. ⁵

What does genetic counselling mean in xeroderma pigmentosum?

Genetic counselling for Xeroderma Pigmentosum (XP) is a vital service that helps individuals and families understand the genetic basis of this condition and its inheritance patterns. In genetic counselling sessions, trained professionals explain the risk of passing XP to future generations, provide information about available genetic testing options, and offer emotional support. They also help individuals and families make informed decisions regarding family planning and assist in exploring options such as prenatal testing or in vitro fertilisation with preimplantation genetic diagnosis to reduce the risk of having a child with XP. Genetic counselling empowers families with the knowledge they need to navigate the challenges associated with XP and make choices that are best suited to their unique circumstances.

Summary

Xeroderma pigmentosum is a genetically inherited condition that increases a person’s sensitivity to UV radiation in the sunlight, leading to sunburns, pigmentation, and a huge increase in skin cancer risk. Usually diagnosed at a young age due to severe sunburns with first exposure, this condition requires strict protection from UVR exposure and regular checkups for skin cancers and eye and neurological problems.