Xeroderma pigmentosum Disease

About Gene:

Xeroderma pigmentosum (XP) is a genetic disease inherited in an autosomal recessive pattern. People suffering from this condition are extremely sensitive to UV rays from sunlight. The disease largely affects the eyes and areas of skin exposed to sunlight. In some cases, patients also experience problems relating to the nervous system. The symptoms of xeroderma (meaning “parchment skin”) pigmentosum become apparent in early childhood or infancy. Most patients have severe sunburn accompanied by redness and blistering after only a few minutes in the Sun. In addition, children develop freckles, dry skin, and skin pigmentation(lentigo). Children with this condition can develop skin cancer as early as 10 years old, with repeated sun exposure increasing the risk of developing precancerous skin lesions (such as actinic keratosis). Patients have a high risk of developing basal skin cancers and melanoma, as well as cancers of the eye, lips, mouth, tongue, neurological disorders such as progressive neuromuscular degeneration, reflex loss, and tumours of the central nervous system. Consanguineous parents have a higher risk of having a child with the condition. The disease affects males and females equally, with the prevalence being higher in Japan,Tunisia, Libya, Egypt,Turkey, Israel,Algeria, Morocco and Syria. In XP, both copies of the genes that code for proteins that work in DNA repair and recognition of DNA damage are not functional. Therefore, DNA damage from UV exposure cannot be repaired. The 9 possible genes that may be non-functional in patients are DDB2 (XP-E),ERCC3 (XP-G), ERCC4 (XP-F), ERCC5 (XP-B), POLH (XP-V or variant), ERCC1, ERCC2 (XP-D), XPA and XPC.

Number of Patients: 2

Disease Causing Genes:

ATR XPC ERCC5 XPA POLH ERCC4 ERCC2 DDB2 ERCC3 DDB1 ERCC1 TP53 HMGB1 GSTM1 GSTT1 XRCC1 ATM PARP1 APEX1 XRCC3 MMP13 SMO NR1H2 KAT2A RAD23B TDG GTF2H1 RAD23A REV3L CETN2 UVRAG MMS19 GEN1 GTF2H5 UVSSA CLEC2A

Sign and Symptoms:

  1. Extreme sunburn after slight sun exposure
  2. Blistering after exposure to sunlight
  3. Xerosis
  4. Atrophy (skin thinning)
  5. Dry eye
  6. Corneal inflammation
  7. Photophobia
  8. Dysphagia
  9. Ataxia
  10. Spasticity
  11. Microcephaly
  12. Loss of cognitive skills
  13. Gradual hearing loss
  14. Vocal cord paralysis
  15. Telangiectasia

Diagnosis:

Diagnoses are typically done on the basis of clinical symptoms. Diagnoses are further confirmed by molecular genetic testing for mutations in the XP genes.

Preventions:

Genetic counselling, avoidance of consanguineous marriage, genetic testing.

Treatment:

Treatment largely involves rigorous sun protection and avoidance, in addition to early detection and treatment of malignant skin lesions. Treatment can include cryotherapy, chemical peeling, surgical excision, etc and topical gels, creams and ointments.