XERODERMA PIGMENTOSUM

Edited by, SOWNDHARYA

Xeroderma Pigmentosum (XP) is a rare inherited skin disorder characterized by a heightened sensitivity to the DNA damaging effects of ultraviolet radiation. The main source of UV is the sun. The symptoms of XP can be seen in any sun exposed area of the body. The effects are greatest on the skin, the eyelids and the surface of the eyes but the tip of the tongue may also be damaged. Approximately 25% age of XP patients also develop abnormalities of the nervous system manifesting as progressive neurodegeneration with hearing loss. People with XP have a 10,000 fold increased risk of developing skin cancer which includes basal cell carcinoma, squamous cell carcinoma and Melanoma.

SIGNS AND SYMPTOMS:

Individuals with XP are particularly sensitive to the DNA damaging effects of UV. Sources of UV include the sun, unshielded fluorescent light bulbs, Mercury vapor lights and halogen light bulbs. Symptoms may differ from person to person, but typically impact the skin, eyes and nervous system. 

Cutaneous effects

• Approximately half of XP patients develop blistering bones 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. 

• Lentigos, are a patchy freckling of the skin that appear before the age of 2 years in XP patients. The lentigos can be seen on all Sun exposed skin, but are often seen first on the face. Lentigos are a sign of unrepaired UV damage in the skin.

• Xerosis 

• Poikiloderma 

• Skin atrophy

• Telangiectasia (a widening of the small blood vessels, which produces red lines and patterns on the skin)

• Actinic keratosis and skin cancers 

OCULAR (EYE) EFFECTS:

• The eyelids and the surface of the eyes exposed to sunlight will usually be affected within the first decade of life.

• Photo phobia is common and is noted in infancy or early childhood

• The conjunctiva (the white portion of the eye) may show sunlight induced inflammation and 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

• Cancers of the eyelids, tissues surrounding the eyes, cornea and sclera can occur very early in life.

NEUROLOGIC (NERVE) EFFECTS:

Approximately 25 % of patients with XP develop a progressive neurodegeneration. The Degeneration can vary in time of onset and rate of progression. Symptoms of the neurodegeneration include

• Acquired microcephaly 

• Diminishing or absent deep tendon reflexes

• Progressive high-frequency sensorineural hearing loss

• Progressive cognitive impairment

• Spasticity (tightness/rigidity of the skeletal muscles), ataxia (poor muscle control and coordination), seizures, difficulty swallowing and or vocal cord paralysis

Neoplasia's (cancer)

• Individuals with XP have a much greater chance of developing certain cancers. The risk of acquiring non-melanoma skin cancers is 10,000 times greater than in the general population.

• Median age of first non-melanoma cancer for XP patients is 9 years old, which is 50 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 dark skinned patients.

CAUSES:

Inheritance

XP is an autosomal recessive genetic disorder. Most genetic diseases are determined by the status of the two copies of a gene, one paternal and the other maternal. Recessive genetic disorders occur when an individual inherits two copies of a non-working gene for the same trait, one from each parent. If an individual inherits one normal gene and one non-working gene for the disease, the person will be a career for the disease but usually will not show symptoms. The risk for two career parents to both pass the altered gene and have an affected child is 25 % with each pregnancy. The risk to have a child who is a career like the parents is 50 % with each pregnancy. The risk for inheriting the disease is the same for males and females.

Parents who are consanguineous have a higher chance than unrelated parents to both carry the same non-working gene, increasing the risk to have children with a recessive genetic disorder.

DIAGNOSIS:

XP is typically first diagnosed on the basis of clinical symptoms. Many patients with XP do not have past family history of the condition. Molecular genetic testing for mutations in the XP genes is available to confirm the diagnosis.

TREATMENT: 

Read about Treatment of XP:

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