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Xeroderma pigmentosum
	Classification and external resources
ICD-10	Q82.1
ICD-9	757.33
DiseasesDB	14198
eMedicine	derm/462 neuro/399
MeSH	D014983

"XP1" redirects here. For the phone, see Sonim XP1 ToughPhone.

Xeroderma pigmentosum has an autosomal recessive pattern of inheritance.

Xeroderma pigmentosa, or XP, is an autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet (UV) light is deficient.^[1]^:574 This disorder leads to multiple basal cell carcinomas (basaliomas) and other skin malignancies at a young age. In severe cases, it is necessary to avoid sunlight completely. The two most common causes of death for XP victims are metastatic malignant melanoma and squamous cell carcinoma^[2]. XP is about six times more common in Japanese people^[2] than in other groups.

The most common defect in xeroderma pigmentosum is an autosomal recessive genetic defect whereby nucleotide excision repair (NER) enzymes are mutated, leading to a reduction in or elimination of NER.^[3] Unrepaired damage can lead to mutations, altering the information of the DNA in individual cells. If mutations affect important genes, such as tumour suppressor genes (e.g. p53) or proto oncogenes, then this disorder may lead to cancer. Patients exhibit elevated risk of developing cancer, such as basal cell carcinoma.

Normally, damage to DNA in epidermal cells occurs during exposure to UV light. The absorption of the high energy light leads to the formation of pyrimidine dimers, namely CPDs (cyclobutane-pyrimidine-dimers) and 6-4PPs (pyrimidine-6-4-pyrimidone photoproducts). The normal repair process entails nucleotide excision. The damage is excised by endonucleases, then the gap is filled by a DNA polymerase and "sealed" by a ligase.

[edit] Types

There are 7 complementation groups, plus one variant form :

Type	Diseases Database	OMIM	Gene	Locus	Also known as/Description
Type A, I, XPA	29877	278700	XPA	9q22.3	Xeroderma pigmentosum group A. Classical form of XP.
Type B, II, XPB	29878	133510	XPB	2q21	Xeroderma pigmentosum group B.
Type C, III, XPC	29879	278720	XPC	3p25	Xeroderma pigmentosum group C.
Type D, IV, XPD	29880	278730 278800	XPD ERCC6	19q13.2-q13.3 , 10q11	Xeroderma pigmentosum group D or De Sanctis-Cacchione syndrome. De Sanctis-Cacchione syndrome can be considered a subtype of XPD.
Type E, V, XPE	29881	278740	DDB2	11p12-p11	Xeroderma pigmentosum group E.
Type F, VI, XPF	29882	278760	ERCC4	16p13.3-p13.13	Xeroderma pigmentosum group F.
Type G, VII, XPG	29883	278780 133530	RAD2 ERCC5	13q33	Xeroderma pigmentosum group G and COFS syndrome type 3.
Type V, XPV		278750	POLH	6p21.1-p12	Xeroderma pigmentosum variant. XPV patients suffer from mutation in a gene that codes for a specialized DNA polymerase called polymerase-η (eta). Polymerase-η can replicate over the damage and is needed when cells enter S-phase in the presence of a DNA-damage.

[edit] Symptoms

Some of the most common symptoms of XP include:

An unusually severe sunburn after a short sun exposure. The sunburn may last for several weeks. The sunburn usually occurs during a child's first sun exposure.
Development of many freckles at an early age
Irregular dark spots on the skin
Thin skin
Excessive dryness of skin
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
Premature aging of skin, lips, eyes, mouth and tongue
Crusting skin
Spidery blood vessels
Scaly skin
Oozing raw skin surface
Limited growth of hair on chest and legs

[edit] Treatment

The most important part of managing the condition is reducing exposure to the sun. The number of keratoses can be reduced with Isotretinoin ([1]) (though there are significant side-effects.) Existing keratoses can be treated using cryotherapy or fluorouracil.^[4]

[edit] Prognosis

Fewer than 40% of individuals with the disease survive beyond age 20 years. Individuals with milder disease may survive beyond middle age.

[edit] In popular culture

Fictional characters with severe cases of XP sometimes play prominent roles in books and movies. Some of the most notable characters include Christopher Snow, the protagonist and narrator of Dean Koontz' Moonlight Bay Trilogy of novels, and the children of the protagonist of Alejandro Amenábar's 2001 film, The Others.

In Taiyou no Uta, a Japanese movie and TV drama of the same name, the protagonist Amane Kaoru has Type A XP.

The condition is featured in the 1994 CBS Movie of the Week, Children of the Dark.

[edit] References

^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0721629210.
^ ^a ^b Li, Lei (January 8, 2007). "Chapter 3 Nucleotide Excision Repair". DNA REPAIR, GENETIC INSTABILITY, AND CANCER. World Scientific Publishing. pp. 75–76. ISBN 9812700145.
^ E. C. Friedberg, G. C. Walker, W. Siede, R. D. Wood, R. A. Schultz and T. Ellenberger (2006). DNA repair and mutagenesis. Washington: ASM Press. p. 1118. ISBN 978-1555813192.
^ Halpern, J.; Hopping, B.; Brostoff, J. (2008). "Photosensitivity, corneal scarring and developmental delay: Xeroderma Pigmentosum in a tropical country". Cases journal 1 (1): 254. doi:10.1186/1757-1626-1-254. PMID 18937855. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577106/.

[edit] See also

[edit] External links

Information

An article about this disorder from DigiLander.iol.it (in English and Italian)
DermNet systemic/xeroderma-pigmentosum

Charities

XP Society
XP Family Support Group
UK Patient Support Group
An article about an untreated XP patient with no access to modernized medical care, with photos.

Halpern, J.; Hopping, B.; Brostoff, J. (2008). "Photosensitivity, corneal scarring and developmental delay: Xeroderma Pigmentosum in a tropical country". Cases journal 1 (1): 254. doi:10.1186/1757-1626-1-254. PMID 18937855. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577106/.

Short films

Sloan Science and Film / Short Films / XP by David Barba 10 minutes
Web Site of a Short Film about an Xeroderma pigmentosum (XP) Patient. Film is directed by Kimberly Williams Paisley

[Andrews-0] James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0721629210.

[Wei-1] Li, Lei (January 8, 2007). "Chapter 3 Nucleotide Excision Repair". DNA REPAIR, GENETIC INSTABILITY, AND CANCER. World Scientific Publishing. pp. 75–76. ISBN 9812700145.

[2] E. C. Friedberg, G. C. Walker, W. Siede, R. D. Wood, R. A. Schultz and T. Ellenberger (2006). DNA repair and mutagenesis. Washington: ASM Press. p. 1118. ISBN 978-1555813192.

[3] Halpern, J.; Hopping, B.; Brostoff, J. (2008). "Photosensitivity, corneal scarring and developmental delay: Xeroderma Pigmentosum in a tropical country". Cases journal 1 (1): 254. doi:10.1186/1757-1626-1-254. PMID 18937855. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577106/.

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