Xeroderma Pigmentosum

XP, attributed by acute sensitivity to sunlight and predisposition to cancer, is an autosomal recessive disease caused by defect in any one of the 7 complementation groups and a single variant. Alterations in these proteins of the NER pathway lead to the declined rate of DNA repair, from which the clinical manifestations of this disease stem. A study in 1968 visibly established a direct link between DNA repair and carcinogenesis by observing that, the cells derived from XP patients were incapable of repairing the ultraviolet (UV) induced DNA damage, hence leading to an increased predisposition to cancer.

The most prominent cutaneous characteristics of XP patients include the parchment of the skin (Xeroderma) and the freckles (pigmentosum), which are remarkably restricted to only the sun-exposed areas of the skin. Also this sun exposure of XP patients generally results in progressive degenerative alterations of the skin and eyes.

Genetics

One of the most frequent defects in XP is an autosomal recessive genetic defect in which nucleotide excision repair (NER) enzymes are mutated, leading to a reduction in or elimination of NER. If left unchecked, damage caused by ultraviolet light can cause mutations in individual cell's DNA. The causes of the neurological abnormalities are poorly understood and are not connected with exposure to ultraviolet light. The most current theories suggest that oxidative DNA damage is generated during normal metabolism in the central nervous system, and that some types of this damage must be repaired by NER. Since DNA repair is under genetic control, it can easily undergo mutations.

The molecular defects in XP cells result in a greatly elevated induction of mutations in sun-exposed skin of affected individuals. This increased mutation frequency probably accounts for the pigmentation changes and the skin cancers. Examination of mutations in the p53 gene in tumors from XP patients reveal p53 mutations characteristic of UV exposure in the majority of tumors. As with all genetic disorders, genetic counseling and psychological support is appropriate for the families, to discuss probability of occurrence in future pregnancies, feelings of isolation and concern about career prospects.

Although there is no cure for xeroderma pigmentosum, the effects can be minimized by getting protection from the sunlight and if possible early removal of precancerous lesions. The most common fate for individuals with XP is early death from cancer due to the fact that they need to take outstanding measures to protect themselves from the dangers of the UV light. But if there is an absence of neurological problems and the individual is always protected or away from sunlight, the prognosis is good.

Types

Symptoms

• Severe sunburn when exposed to only small amounts of sunlight. These often occur during a child's first exposure to sunlight.
• Development of many freckles at an early age.
• Rough-surfaced growths (solar keratoses), and skin cancers.
• Eyes that are painfully sensitive to the sun and may easily become irritated, bloodshot and clouded.
• Blistering or freckling on minimum sun exposure.
• Spider Veins
• Limited growth of hair on chest and legs.
• Scaly skin
• Dry skin
• Irregular dark spots on the skin
• Corneal ulcerations

Treatments

The most obvious, and often important part of treatment, is avoiding exposure to sunlight. This includes wearing protective clothing and using sunscreen (physical and chemical).Keratosis can also be treated using cryotherapy or fluorouracil.

Prognosis

Fewer than 40% of individuals with the disease survive beyond the age of 20. Some XP victims with less severe cases do manage to live well into their 40s.

Popular Citations

• Halpern J, Hopping B, Brostoff J (2008). "Photosensitivity, corneal scarring and developmental delay: Xeroderma Pigmentosum in a tropical country"
• James W, Berger T, Elston D (2005). "Andrews' Diseases of the Skin: Clinical Dermatology".