Xeroderma pigmentosum
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A child develops severe sunburns after minimal sun exposure and has freckling in sun-exposed areas by age 2. By age 10, he develops multiple skin cancers.
AR; nucleotide excision repair (NER) genes
- 8 complementation groups: XPA-XPG, XPV (POLH)
- XPC most common
- Extreme sun sensitivity (severe burns with minimal exposure)
- Freckling in sun-exposed areas (early childhood)
- Multiple skin cancers (BCC, SCC, melanoma) - 1000-fold increased risk
- Ocular abnormalities (photophobia, keratitis, tumors)
- Progressive neurological degeneration (~30%, especially XPA)
- Median age of first skin cancer: 8-9 years
- Clinical suspicion from extreme photosensitivity (severe sunburn after minimal exposure), early sun-exposed freckling, and very early-onset skin cancers
- Functional/laboratory confirmation: cultured fibroblasts show reduced unscheduled DNA synthesis and impaired post-UV survival, reflecting defective nucleotide excision repair
- Confirm and subtype with germline testing across the complementation groups (XPA-XPG and POLH/XPV); XPC is most common, and XPA variants carry the highest neurodegeneration risk
- Strict UV protection (sunscreen, protective clothing, UV-blocking windows)
- Regular dermatologic surveillance (every 3-6 months)
- Early excision of skin cancers
- Neurological monitoring
xERo-derma has "Xero" (zero) Excision Repair activity: XP = nucleotide eXcision repair defect. "Xero" = dry, "derma" = skin, "pigmentosum" = abnormal skin pigmentation from sun sensitivity.
"NER in XERoderm" (N and X both have 4 "points"): XP involves nucleotide excision repair (NER). Cannot repair T-T dimers ("XeroDimer") caused by UV damage. UV is close to X in the alphabet.
XP for "Xcision" repair: Three disorders involve NER: Xeroderma pigmentosum, Cockayne syndrome, and Trichothiodystrophy. For "TTD", turn the "t" 45 degrees clockwise and you get another "X" for "Xcision".
This overview breaks down the disease name: "Xero" = dry, "derma" = skin, "pigmentosum" = abnormal pigmentation from sun hypersensitivity, with "xERo" encoding zero nucleotide Excision Repair (NER) activity.
