 Xeroderma Pigmentosum (XP) is

a rare genetic disorder that occurs

worldwide in all races and ethnic
groups.
 First described by Hebra and
Kaposi in 1874 the disorder is
characterised by marked
photosensitivity and premature
onset of all major types of skin
cancer.
 It is characterised by inability of a
cell to repair damage caused by
UV leading to genetic instability
and skin cancer.
 Usually found at very young age(1-2yrs).
 XP affects approximately one in 1,00,000
individuals worldwide.
 One in 250,000 persons in the United States
and Europe.
 Six times more common in Japanese people
than in any other groups.
 The products of seven of XPgenes (XP-A through G) are
involved in the repair of ultraviolet-induced
photoproducts in DNA by the process of nucleotide
excision repair (NER)5.
 The XPC and XPE proteins are needed to recognise the
photoproducts in DNA.
 XPB and XPD are part of a protein complex TFIIH, which
opens up the structure of the DNA around the site of
the photoproduct.
 XPA protein verifies that proteins are in the correct
position and then the nucleases XPG and XPF cut the
DNA on either side of the damage, so that the damaged
section can be removed and replaced with intact DNA.
 Patients defective in the XPC or XPE genes do not, in
general, have the extreme sunburn reactions or
neurological abnormalities.
 Defects in the eighth XP gene do not affect NER .
 The DNA polymerases that normally replicate DNA
cannot deal with damage in the DNA template and
specialised polymerases have to be employed to get
past the damage (translesion synthesis).
 For UV damage, the cell uses DNA polymerase η,
encoded by the gene POLH and this gene is mutated in
XP-V patients .
 Like XP-C and XP-E patients, XP-V patients rarely have
extreme sunburn reactions or neurological problems.
 Autosomal recessive genetic disorder.
 Nucleotide excision repair(NER) enzymes are
mutated.
 Reduced or eliminated number of NER
enzymes.
 Metastatic malignant melanoma.
 Squamos cell carcinoma.
 In recessive disorders, the condition does not
appear unless a person inherits the same
defective gene for thesame trait from each
parent.
 If an individual receives one normal gene and
one genefor the disease, the person will be a
carrier for the disease.
 The risk of transmitting the disease to the
children of a couple, both of whom are carriers
for a recessive disorder, is 25 percent. Fifty
percent of their children risk being carriers of
the disease.
 Severe sunburn.
 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
Before birth:
 Amniocentesis
 Chorionic villous sampling
After birth:
 Severe sunburn after first exposure to the
sunlight.
 Based on clinical findings and family
history,skin, eye, and nervous system.
 By measuring the DNA repair factor from skin
or blood sample.
 Cryotherapy
Removal of heat from the body.

 Fluorouracil
Pyrimidine analogue used to treat cancer.

 Reduced exposure to sun’s UV rays

 Many patients die at an early age from skin cancers
but if a person is diagnosed early, does not have
severe neurological symptoms and takes all the
precautionary measures to avoid exposure to UV
light, they may survive beyond middle age.

Less than 40% of individuals with the disease survive

beyond age 20.

Some with less severe cases manage to live well up to 40

years.
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