Xeroderma Pigmentosum, a Rare Genetic Condition

Around half of people with xeroderma pigmentosum develop blistering burns on their skin after a short amount of sun exposure. Often, less than 10 minutes of exposure causes burns that take over a week to heal. Nearly every individual who has xeroderma pigmentosum experiences an onset of lentigos after sun exposure. This skin freckling is a sign of UV damage. For these people, frequent sun exposure can cause severely dry skin, patches of lighter skin color, thinning of the skin, and spider veins.

Within the first decade of life, xeroderma pigmentosum will also affect the eyelids and eyes. Light sensitivity is common, typically appearing in infancy. Inflammation may develop in the cornea, conjunctiva, and eyelids. Over time, dry eye can become a chronic issue that leads to severe symptoms. All of these effects contribute to vision loss or blindness. Sun exposure may cause the eyelids to become thinner and the eyelashes to fall out, leaving the eyes without proper protection.

Roughly one-fourth of people with xeroderma pigmentosum will experience progressive neurodegeneration. Symptoms of this can vary, but may include

• Acquired microcephaly or smaller head size
• Diminishing or fully absent deep tendon reflexes
• Hearing impairments including hearing loss
• Ataxia, or poor muscle coordination and control
• Cognitive impairment
• Short stature
• Developmental delays
• Spasticity or tightness of muscles
• Seizures
• Difficulty swallowing
• Vocal cord paralysis

People who have xeroderma pigmentosum have a much higher risk of developing certain types of cancer. Cancerous growth can begin as early as age four, though the average is age eight. The disease more commonly affects areas with greater sun exposure, such as the face and arms. The most common cancers that affect individuals with xeroderma pigmentosum are skin cancers such as basal cell carcinoma, squamous cell carcinoma, and melanoma.

Experts have recognized certain genes with links to xeroderma pigmentosum. There are eight subtypes of xeroderma pigmentosum, and each subtype is associated with a specific mutation in a different gene. These genetic mutations cause these genes to work incorrectly or fail to function entirely. In each subtype, the gene's ability to function is damaged by the UV light.

Xeroderma pigmentosum has an autosomal recessive inheritance pattern in the majority of cases. This means that a person must inherit an altered gene from both of their parents to develop the condition. If an individual only has one of these genes, they become a carrier and usually have no symptoms. If two carriers have a child, there is a 25% chance that the child will have xeroderma pigmentosum.

Doctors diagnose xeroderma pigmentosum through clinical examination of the symptoms. They confirm the diagnosis through genetic testing. Some experts test skin cells to discover a sensitivity to ultraviolet light. Usually, diagnoses for xeroderma pigmentosum occur in early infancy because the child develops a severe sunburn after minor sun exposure.

No cure exists for xeroderma pigmentosum, so medical experts focus on managing symptoms. People with the condition should avoid cigarette smoke, sunlight, and any form of ultraviolet radiation. Often, this involves wearing full-coverage clothing and growing their hair long. Vitamin D supplements are often necessary because they cannot spend time in sunlight, the main way to obtain the nutrient. Lubricating eye drops can help with some eye symptoms and certain creams and lotions can help with the condition’s skin effects. Some people require hearing aids or other devices to manage their hearing loss. Older adults with xeroderma pigmentosum often use wheelchairs to remain mobile.

Because the condition is rare, it is difficult to determine its exact incidence. Studies report that between one in 250,000 and one in 1 million people have xeroderma pigmentosum in the United States. The condition is more common in Japan, North Africa, and the Middle East. Because of the condition’s inheritance pattern, females and males are equally affected.

Many people with xeroderma pigmentosum die before middle age due to skin cancer. Because of this, the average life expectancy of a person who has the condition without neurological symptoms is 37 years. This drops to 29 years if they have neurological issues. With proper precaution, care, and a lack of certain symptoms, a person with xeroderma pigmentosum can live past middle age.