SNP Shot: Genomic Insights

Xeroderma pigmentosum (XP) is a genetic disorder causing extreme sensitivity to ultraviolet (UV) radiation, found in sunlight and some artificial lights. It primarily affects sun-exposed skin and the eyes. XP elevates the risk of UV-induced cancers and often leads to premature aging. Some individuals with XP also experience neurological issues.

Symptoms of XP typically appear in infancy or early childhood. Around half of affected children experience severe sunburns after brief sun exposure, resulting in redness and blisters that can persist for weeks. However, some children with XP can tan normally.

By age two, almost all children with XP develop freckling on sun-exposed areas like the face, arms, and lips, a rare occurrence in young children without the condition. Sunlight exposure in affected individuals often leads to dry skin (xeroderma) and changes in skin pigmentation, giving the condition its name.

Individuals with XP have a significantly higher risk of developing skin cancer compared to those without the condition. They are approximately 10,000 times more likely to develop non-melanoma skin cancer and up to 2,000 times more likely to develop melanoma. Common skin cancers include basal cell carcinoma, squamous cell carcinoma, and melanoma. The first skin cancer usually appears before age 10.

Without sun protection, most individuals with XP develop multiple skin cancers throughout their lives, primarily on sun-exposed areas like the face, lips, eyelids, scalp, and tongue. Studies suggest a possible increased risk of internal cancers, including brain tumors, thyroid cancer, and blood cancers. Smoking further elevates the risk of lung cancer in affected individuals.

The eyes of individuals with XP can be extremely sensitive to UV radiation (photophobia). Without protection, the eyes may become bloodshot and irritated, and the cornea can become cloudy. Eyelash loss and abnormal eyelid turning may also occur. In addition to cancer risk, XP is linked to noncancerous eye growths, and many of these eye abnormalities can impair vision.

About 30% of individuals with XP develop progressive neurological abnormalities alongside skin and eye issues. These may include hearing loss, poor coordination, walking difficulties, movement problems, intellectual decline, difficulty swallowing and speaking, and seizures. These neurological problems tend to worsen over time.

Individuals with XP may experience early menopause.

Researchers have identified at least eight genetic forms of XP: complementation groups A through G, and a variant type (XP-V). These types are differentiated by their genetic cause. While all types increase skin cancer risk, some are more prone to causing neurological abnormalities.

Inheritance:

XP follows an autosomal recessive inheritance pattern. This means that both copies of the responsible gene in each cell must be mutated for the disorder to manifest. Parents of an individual with XP each carry one copy of the mutated gene but typically do not exhibit symptoms themselves.