1. Background

• considered to be a "chromosome breakage syndrome"
  • one of at least 4 disorders associated with a high frequency of chromosomal defects with an increased risk of lymphoreticular (leukemia) and other malignancies
  • other syndromes:
    • Ataxia-Telangiectasia
    • Bloom Syndrome
    • Fanconi Anemia

2. Genetic Defect

• genetic defect -> defect in UV-induced DNA repair mechanisms (but not x-ray-induced DNA repair mechanisms) -> sensitivity of skin to wavelengths between 280-340 nm -> skin cells unable to repair sunlight-induced DNA damage -> damage to sun-exposed areas (face, neck, hands, arms)
• genetic defect may be related to a deficiency of DNA endonuclease
• eight to ten subtypes of XP have been identified termed complementation groups A through I
  • separated into groups on the basis of group's ability to repair damaged DNA
  • Groups A, C, D, and Variant
    • make up over 90% of cases of XP
    • Group A - show the lowest level of DNA repair and have the most neurological manifestations
    • Group C - show the highest level of DNA repair
    • Variant - later onset of disease and has a defective postreplication DNA repair
• light from unshielded fluorescent bulbs and sunlight passing throught glass windows may also be dangerous

3. Chromosomal Abnormalities

• no chromosomal breaks, gaps, and rearrangements
• clones of cells with chromosomal abnormalities
• increased frequency of UV-induced chromosome breaks and sister chromatid exchanges

1. Cutaneous Manifestations

• affected areas first noted in infany or early childhood
• initial manifestations
  • photosensitivity with blistering on minimal sun exposure and/or freckling upon exposure to UV light
• later manifestations
  • atrophy
  • bullae
  • crusting
  • erythema
  • freckles
  • keratoses
  • lentigines
  • scaling
  • telangiectasia

2. Ocular Manifestations

• blepharitis
• keratitis
• lacrimation
• corneal opacities -> blindness
• photophobia
• symblepharon

3. Other Manifestations

1. Serum

• no deficiencies of immunoglobulins

1. Supportive

• no treatment available
• avoid sunlight:
  • protective clothing, sunglasses, sunscreens
• surveillance for and treatment of all neoplasms

Xeroderma Pigmentosum Society Inc.