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هدى البيان

on 19 May 2014

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3-year-old boy, was referred to the dermatology clinic for evaluation of severe sun sensitivity and freckling.
On physical examination:
he was photophobic
had conjunctivitis
prominent freckled hyperpigmentation in sun-exposed area
His development and physical examination were otherwise normal.

the child is for non consanguineous Japanese parents; no one else in the family was similarly affected.

The dermatologist explained that child had classic features of xeroderma pigmentosum, that is"parchment-like pigmented skin".

What's the phenotype and natural history of XP ?

Confirmation of the diagnosis of XP relies on functional tests of DNA repair and UV sensitivity such tests are usually performed on cultured skin fibroblasts.

Diagnostic confirmation by identification of mutations in an XP-associated gene is not currently clinically available.

In the United States and Europe, the prevalence is approximately 1 in 1 million .

In Japan, the prevalence is 1 in 100,00 .
Xeroderma Pigmentosum
Clinical case
Xeroderma pigmentosum

A rare disorder transmitted in an autosomal recessive manner.

It is characterized by :
occurs at childhood
pigmentary changes
premature skin aging
malignant tumor development.

Variable expressivity
Genetic heterogeneity
Genetic complementation
Caretaker tumor-suppressor genes
What's the cause

Defect in ( Nucleotide Excision Repair).

Repair of damaged DNA by UV irradiation occurs by three mechanisms :

-Excision Repair

Postreplication Repair


Nucleotide excision repair is a complex but versatile process involving at least 30 proteins.

The basic principle is the removal of a small single-stranded DNA segment containing a lesion by incision to either side of the damaged segment and subsequent gap-filling repair synthesis with use of the intact complementary strand as a template.

Nucleotide excision repair
XP is caused by mutations affecting :

the global genome repair subpathway of nucleotide excision repair
or by mutations affecting postreplication repair.

In contrast, Cockayne syndrome a related disorder is caused by mutations affecting the transcription-coupled repair

XP and Cockayne syndrome have been separated into 10 biochemical complementation groups .

The reduced or absent capacity for global genome repair or postreplication repair represents a higher level of oncogene and tumor-suppressor gene mutations than have tumors from the normal population, and those mutations appear to be highly UV specific.

Cutaneous neoplasms detected in those patients .
first stage
second stage
The appearance of malignancies:
squamous cell carcinomas
malignant melanoma
basal cell carcinoma

These malignancies may occur as early as age 4-5 years and are more prevalent in
sun-exposed areas .

skin healthy at birth
3 stages ?
appears after age 6 months.

This stage is characterized by :

diffuse erythema, scaling, and freckle like areas of increased pigmentation.

seen with over light-exposed areas, appearing initially on the face.

With progression of the disease, the skin changes appear on the lower legs, the neck, and even the trunk in extreme cases.

These features tend to diminish during the winter months with decreased sun exposure.

as time passes, these findings become permanent.
Poikiloderma consists of :

skin atrophy,
mottled hyperpigmentation and hypopigmentation .

giving rise to an appearance similar to
that of chronic radiodermatitis .

Third stage
60% to 90% of patients experience ocular abnormalities :

photophobia, conjunctivitis, blepharitis, ectropion, and neoplasia.
distribution of ocular damage and neoplasms corresponds to the sites of greatest UV exposure.

Approximately 18% of patients experience progressive neuronal degeneration.

Features include sensorineural deafness, mental retardation, spasticity, hyporeflexia or areflexia, segmental demyelination, ataxia, choreoathetosis, and supranuclear ophthalmoplegia.
Two related disorders, Cockayne syndrome and trichothiodystrophy are also caused by defects in other components of the cellular mechanism for repair of UV-induced DNA damage.

Both are characterized by :

poor postnatal growth
diminished subcutaneous tissue
joint contractures
thin papery skin with photosensitivity
mental retardation, and neurological deterioration.

management by :
careful surveillance for and excision of cutaneous malignant neoplasms.

No curative treatments are currently available.
physical and chemical sunscreens
avoidance of exposure to sunlight

protective clothing


XP is an
autosomal recessive
disease .......
many patients do not have a family history of the disease.
For parents who already have a child affected with XP, the risk for future children to have XP is 1 in 4.

Prenatal diagnosis is possible by functional testing of DNA repair and UV sensitivity in cultured amniocytes or chorionic villi.

The results of this testing confirmed the diagnosis of xeroderma pigmentosum.

Despite appropriate preventive measures, he developed metastatic melanoma at 15 years of age an died 2 years later.

His parents had two other children; neither was affected with xeroderma pigmentosum.
To confirm the diagnosis that he had a skin biopsy to evaluate DNA repair and ultraviolet (UV) radiation sensitivity in his skin fibroblasts.

References :

Thank you
Prepared by :

Somaya Aref Al-hout

supervisor :
Dr. Basim Ayesh
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