Xeroderma pigmentosum (XP) is a rare genetic disorder characterized by extreme sun sensitivity and a very high risk of skin cancer. It is caused by an inability to repair UV damage to DNA. Patients with XP often experience severe sunburn, freckling, and skin pigmentation changes at an early age, along with a greatly increased risk of developing skin cancers. Some patients also experience neurological problems like cognitive decline. Strict sun avoidance and regular skin exams are important for management.

1. Nikhil Ranjan Das
XERODERMA
PIGMENTOSUM

2. ELECTROMAGNETIC SPECTRUM OF SUN LIGHT

7. HEADINGS
• Introduction
• Causes
• Aetiology
• Signs and Symptoms
• Diagnosis
• Treatment
• Prognosis
• Prevention
• Conclusion

8. INTRODUCTION
• Rare genetic disorder that occurs
worldwide in all races and ethnic
groups.
• First described by Hebra and Kaposi
in 1874.
• Photosensitivity and premature
onset of all major types of skin
cancer .
• Inability of a cell to repair damage
caused by UV leading to genetic
instability and skin cancer.
Mortiz Kaposi

9. DEFINITION
• Xeroderma pigmentosum (XP) is a rare autosomal
recessive disorder of DNA repair.
• It is characterized by progressive pigmentary changes at
exposed sites, an increased risk of ultraviolet radiation
(UVR) induced skin and mucous membrane cancers,
severe photosensitivity in about 50%, and
neurodegeneration in approximately 30% of affected
cases.

10. INCIDENCE
• 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.

11. Exposure to UV light
Thymine dimer
DNA damage
No replication of DNA strand
.
NER
NUCLEOTIDE EXCISION REPAIR(NER)

12. NUCLEOTIDE EXCISION REPAIR(NER)
• Responsible for removing the damaged segments of DNA and
restoring the original sequence of DNA.
• The NER mechanism is composed of two types:
• Transcription coupled(TCR): Which rapidly repairs areas of
DNA that are "active" and being
transcribed into RNA
• Global genome(GGR): Which repairs damage in the
rest of the genome more slowly
• Seven XP genes are central to NER which includes many other
accessory proteins

15. COMPLEMENTATION GROUP
• The term “complementation group” is based on cell fusion
experiments.
• Cells from different XP patients are fused to investigate if the
DNA repair defect in the fused cells is corrected.
• If DNA repair in the fused cell is increased, each cell provides
proteins that the other is lacking and the cells “complement”
each other and are in different complementation groups.
• If DNA repair in the fused cells is not normalized, the cells do not
“complement” each other, meaning that both cells harbor
mutations in the same DNA repair gene.
• Seven such complementation groups have been identified (XP-A
to XP-G), which correspond with mutations in seven distinct
genes that can cause XP.

17. CLINICAL FEATURES

18. CLINICAL FEATURES
The clinical manifestations,
Severity of disease &
Age of onset
Cumulative UVR exposure,
The complementation group &
Precise nature of the pathogenic mutation.

19. EXAGGERATED SUNBURN &
PIGMENTARY CHANGES
• Severity changes is dependent on
the amount of sun exposure and
the degree of UVR protection
• Acute and severe sunburn on
minimal sun exposure takes weeks
to resolve.
• 50% of XP patients suffer from
severe and prolonged sunburn
reactions.
• Rest 50% have sunburn reactions
that are normal and present with
lentigines as well as
hypopigmented macules.

20. PIGMENTARY CHANGES
• Development of many freckles at
an early age.
• Rough-surfaced growths (solar
keratoses), and skin cancers
• Blistering or freckling on minimum
sun exposure
• Telangiectasia (spider veins)
• Limited growth of hair on chest
and legs
• Scaly skin• Xeroderma (dry skin)
• Irregular dark spots on the skin
• Poikiloderma (a mixture of both hyper (increased) and hypo
(decreased) skin pigmentation

21. SKIN CANCER
• Absorption of UVR by DNA results in
the formation of photoproducts (CPDs
and 6‐4PPs) - Classic ‘UVB signature’
• 10 000‐fold increased risk of
developing non‐melanoma skin cancer
(NMSC).
• 2000‐fold increased risk of melanoma
skin cancer
• The median age at diagnosis of first
NMSC is 9 years
• The median age at diagnosis of first
melanoma is 22 years.

22. SKIN CANCER
• UVR exposure to the
oral cavity in results
in mucocutaneous
malignancy.
• Most common is
squamous cell
carcinoma of the tip
of the tongue

23. OTHER MALIGNANCIES
• Damage caused by cigarette smoke
(benzopyrene) is repaired by NER.
• XP patients are potentially at higher
risk of smoking‐induced lung
cancers.
• 50‐fold increase in cancers of the
brain, including medulloblastoma,
glioblastoma, spinal cord
astrocytomas and schwannoma
• High‐dose X‐ray irradiation can be
used for the treatment of brain
tumours as the pathways involved in
the repair of DNA damage by X‐rays
are normal in patients with XP.

24. OCULAR MANIFESTATIONS
• Conjunctiva develops
UVR‐related damage dry eye,
conjunctival injection and
inflammation, premature
pingueculae and pterygia.
• Corneal scarring and visual
impairment are common.
• Ocular surface cancers mainly
squamous cell carcinomas.
• Neuro‐ophthalmological features including sluggish pupils,
nystagmus and strabismus.
• Photophobia is common and the earliest presenting
ophthalmic symptom.

25. NEURODEGENERATION
• 30% of XP patients develop
neurodegeneration.
• The age at onset and rate of
progression varies with degree
of mutations.
• In the absence of functional
repair, the lesions persist and
result in neuronal cell death.
• Neurological manifestations do
not arise before the age of 2
years XP patients are born
normal

26. • Mild cognitive impairment first,
when the child is starting school.
• Cerebellar signs manifest between 4
and 16 years of age, commonly
dysarthria and difficulties with
balance.
• Magnetic resonance imaging
demonstrates atrophy of the cortex
of the brain with concomitant
dilatation of the ventricles.
• Most develop sensorineural
deafness which has been shown to
predict future neurological
involvement.
NEURODEGENERATION

27. PSYCHOLOGICAL MORBIDITY
• UVR‐protective
clothing restrictions
(such as a facial visor)
in many patients with
XP can result in social
isolation and
depression.
• Surgical procedures
for skin cancers,
many on the face,
with associated
disfigurement.

28. DIFFERENTIAL DIAGNOSIS
• Trichothiodystrophy
• Cockayne syndrome
• Cerebro‐oculo‐facio‐skeletal syndrome
• UV‐sensitive syndrome
• Erythropoietic protoporphyria
• Rothmund–Thomson syndrome

29. MANAGEMENT
• Application of high‐factor sunscreen.
• UVR‐protective clothing, sunglasses, and UVR
blocking window films (at home and in cars).
• Vitamin D deficiency is common and
supplements should be prescribed..
• Retinoids may have a role in the prevention of
skin cancer.
• Regular skin and eye review and appropriate
and early management of any cancers is
essential.
• Topical 5‐fluorouracil and imiquimod are
useful for early or premalignant lesions.
• The eyes need to be treated with lubricating
drops.
• Patients should be given appropriate genetic
counselling.

30. PROGNOSIS
• There is no cure for XP.
• The overall median age of death is 32 years.
• Skin cancer and neurodegeneration the main causes of
death.
• Sun avoidance and regular follow‐up increases life
expectancy.
• The neurological abnormalities are progressive and the
median age at death in these patients (29 years) is
significantly younger than in XP patients without
neurological degeneration (37 years)

31. CONCLUSION
• There is no cure for XP.
• Increased awareness and
early diagnosis, followed by
protection from daylight and
careful patient
management,
• These measures improve the
quality of life and life
expectancy of affected
individuals.