Rare inherited skin disorder due to defective repair of DNA characterized by; photosensitivity, pigmentary changes, premature skin aging, early malignant tumor development

1. Xeroderma Pigmentosum
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11. XP

12. What is XP?

13. Rare inherited skin disorder
due to defective repair of DNA
characterized by;
photosensitivity
pigmentary changes
premature skin aging
early malignant tumor development

15. How Is It Inherited?

16. Autosomal recessive

19. What About Its Presentation?

28. Is It a Pure Skin Disorder?

29. Skin
Eyes
Brain

33. What Are The Tumors
That Can Develop In XP?

34. BCC
SCC
keratoacanthoma
malignant melanoma

39. What Is NER?

40. Nucleotide Excision Repair

41. It is a mechanism of DNA repair
used in repairing UV damage

42. Nucleotide
Excision Repair

43. NER in the cell
Damage Recognition
Binding of protein complex
3’
Incision of DNA
5’
Oligonucleotide excision
DNA repair synthesis

44. What Is The Cause Of XP?

45. If mutation affect the important genes, this can lead to
serious disease
For example: p53, tumor suppressor genes, this order can lead to
cancer
Reduction or elimination of NER
Unrepaired damage can lead to mutations, changing the information
of the DNA in the individual
Nucleotide excision repair (NER) enzymes are mutated
NER - DNA repair mechanism

46. DNA damage causes mutations
that activate oncogenes
or
inactivate tumor suppressor genes

48. What are The Different Types Of XP?

49. XP is actually the name of 8 different gene
abnormalities in 8 locations

50. At least 8 different gene abnormalities or
complementation groups (XPA to XPG)  varying
disease severity

52. Type Gene Locus
Type A, I, XPA XPA 9q22.3
Absent or minimal
DNA repair activity
Type B, II, XPB XPB 2q21 Few patients
Type C, III, XPC XPC 3q25
Most common, 1/3 of
all patients
Type D, IV, XPD
XPD
ERCC6
19q13.2-q13.3, 10q11
Second most
common
Type E, V, XPE DDB2 11p12-p11
Type F, VI, XPF ERCC4 16p13.3-p13.13
Type G, VII, XPG
RAD2
ERCC5
13q33
Dominant Type

54. What You Can See In XP Biopsy?

60. How Can XP Be Treated?

61. No “cure” for XP exists yet

62. The best thing to do
is to avoid contact with UVR

66. Reducing exposure to the sun
Sun glasses
Clothing (long sleeves, long pants, gloves)
Optical filtration
Lots and lots of sunscreens

67. HOUSING
Halogen or LED lamps
Special windows are required everywhere with
UV-Blocking films

69. Isotretinoin may reduce the number of keratosis &
prevent formation of new cancers

70. early & complete removal
of all tumors is essential

71. Cryo
5-FU

72. Regular follow-up

73. Gene Therapy

75. What Is The Prognosis Of XP?

76. Many patients with XP die at an early age from
skin cancers
Less than 40% of individuals with XP survive
beyond age 20 years

77. However, if a person is diagnosed early,
does not have severe neurological symptoms,
has a mild variant,
and takes all the measures to avoid UVR,
they may survive beyond middle age

79. References
dermnetnz.org
Google images
en.wikipedia.org
Bolognia Textbook of Dermatology 3rd ed
Genetic Disease By: Jean Liu (Presentation)

80. THANK YOU