Individuals with XP are particularly sensitive to the DNA damaging effects of UV. Sources of UV include the sun, unshielded florescent light bulbs, mercury vapor lights and halogen light bulbs. Symptoms may differ from person to person, but typically impact the skin, eyes, nervous system. Patients with XP may develop multiple thyroid nodules, premature menopause or leukemia.
Cutaneous (Skin) Effects Approximately half of XP patients develop blistering burns on sun exposed skin after minimal sun exposure (sometimes less than 10 minutes in the sun). These burns evolve over several days and may take greater than a week to heal. Sometimes these burns are so severe, child abuse is suspected. The other 50% of XP patients do not burn, but tan after sun exposure. However, both types of sun reactions result in the early onset of lentigos (freckling) of the skin.
Lentigos, are a patchy freckling of the skin that often appear before the age of two years in XP patients. The lentigos can be visible on all sun exposed skin but are often seen first on the face. Lentigos are a sign of unrepaired UV damage in the skin. Repeated sun exposure also results in xerosis (dry, parchment-like skin) and poikiloderma a mixture of both hyper (increased) and hypo (decreased) skin pigmentation, skin atrophy (thinning of skin tissue), and telangiectasia (a widening of the small blood vessels, which produces red lines and patterns on the skin). In people who do not have XP, poikiloderma is typically seen in older adults, who work outdoors, such as farmers or sailors, with many years of sun exposure.
For people with XP continuous repeated sun exposure has severe effects, resulting in the early development of precancerous skin lesions (such as, actinic keratosis) and skin cancers (see below).
Ocular (Eye) Effects The eyelids and the surface of the eyes exposed to sunlight will usually be affected within the first decade of life.
Photophobia (light sensitivity, or Pain upon seeing light) is common and is often noted in infancy or early childhood. The conjunctiva (the white portion of the eye) may show sunlight induced inflammation. People with XP also develop dry eye. Symptoms of dry eye include a feeling of ‘something being in the eye’, constant irritation and Redness of the eye. Dry eye can result in chronic inflammation and keratitis. Keratitis, or inflammation of the cornea (the clear outer portion of the eye) may also occur in response to sunlight. In severe cases, keratitis can result in corneal opacification (lack of transparency) and vascularization (an increase in blood vessel density). These combined effects may obscure vision, leading to blindness. With repeated sun exposure, the lids of the eyes may atrophy (degenerate) and eyelashes may fall out, leaving the eyes unprotected and contributing to vision loss.
Cancers of the eyelids, tissues surrounding the eyes, cornea and sclera (white part of the eye) can occur very early in life. Surgeries to remove ocular cancers can lead to lid abnormalities resulting in difficulty completely closing the eyes and vision loss. When cancers in or near the eye are large or invasive, the globe of the eye may need to be removed.
Neurologic (Nerve) Effects Approximately 25% of patients with XP develop progressive neurodegeneration. The degeneration can vary in time of onset and rate of progression. Symptoms of neurodegeneration include: acquired microcephaly (a condition marked by smaller head size and structural changes in the brain), diminishing (or absent) deep tendon reflexes, progressive high-frequency sensorineural hearing loss (deafness caused by damage to the nerves of the inner ear), progressive cognitive impairment, spasticity (tightness/rigidity of the skeletal muscles), ataxia (poor muscle control and coordination), seizures, Difficulty swallowing and/or vocal cord paralysis.
These issues are thought to arise due to the loss of nerve cells in the brain. On imaging such as MRI or CT scans, the brains of XP patients with neurologic degeneration show atrophy (shrinkage) with marked dilation of the ventricles (fluid filled spaces in the middle of the brain). It is thought that accumulating unrepaired DNA damage in the brain cells results in their death, however, the source of this damage has not been identified.
Neoplasias (Cancer) Individuals with XP have a much greater chance of developing certain cancers. The risk of acquiring non-melanoma skin cancers (e.g., basal cell carcinoma and squamous cell carcinoma) is 10,000 times greater than in the general population in patients under 20 years of age. Median age of first non-melanoma cancer for XP patients is 9 years old, which is 50 years earlier than in the general population. For melanoma skin cancer, the risk is 2,000 times greater for those with XP. The median age of onset is 22 years, which is 30 years earlier than in the general population.
Oral cavity neoplasms, specifically squamous cell carcinoma of the tip of the tongue (a non-pigmented sun exposed area), is common especially in XP patients who live in very sunny and warm climates. Internal cancers that have been reported in individuals with XP include: glioblastoma of the brain, astrocytoma of the spinal cord, and cancer of the lung in patients who smoke, and rarely, leukemia (cancer of the white blood cells). Cancers of the thyroid, uterus, breast, pancreas, stomach, kidney, and testicles have also been reported.