Xeroderma pigmentosum

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

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

Xeroderma pigmentosum has an autosomal recessive pattern of inheritance.

Xeroderma pigmentosum, 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 In extreme cases, all exposure to sunlight must be forbidden, no matter how small. Multiple basal cell carcinomas (basaliomas) and other skin malignancies frequently occur at a young age in those with XP. In fact, metastatic malignant melanoma and squamous cell carcinoma^[2] are the two most common causes of death in XP victims. This disease involves both sexes and all races, with an incidence of 1:250,000 and a gene frequency of 1:200. XP is roughly 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 in which nucleotide excision repair (NER) enzymes are mutated, leading to a reduction in or elimination of NER.^[3] If left unchecked, damage caused by ultraviolet (UV) light can cause mutations in individual cell's DNA. If tumor suppressor genes (e.g. p53) or proto oncogenes are affected, the result may be cancer. Patients with XP are at a high risk for developing skin cancers, such as basal cell carcinoma, for this reason.

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 cyclobutane-pyrimidine dimers) and pyrimidine-6-4-pyrimidone photoproducts). In a healthy, normal human being, the damage is first excised by endonucleases. DNA polymerase then repairs the missing sequence, and ligase "seals" the transaction. This process is known as nucleotide excision repair.

Types

There are seven 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 - the 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 (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 - these 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.

Symptoms

Some of the most common symptoms of XP include:

• A severe sunburn when exposed to only small amounts of sunlight. Often occurring during a child's first exposure to sunlight.
• 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
• Spidery blood vessels
• Oozing raw skin surfaces
• Limited growth of hair on chest and legs
• Scaly skin
• Irregular dark spots on the skin

Treatment

The most obvious, and often important part of treatment, is avoiding exposure to sunlight. Keratoses can also be treated using cryotherapy or fluorouracil.^[4] A few places specialize in XPS treatment, one of most notable being Camp Sundown in Craryville, New York.

Prognosis

Fewer than 40% of individuals with the disease survive beyond age 20 years. Some XP victims with less severe cases do manage to live well into their 40s.

In popular culture

These fictional characters have XP:

• Christopher Snow in Dean Koontz's Moonlight Bay Trilogy
• In the 2002 novel Going Out by Scarlett Thomas, Luke
• Children of the main character in Alejandro Amenábar's 2001 film, The Others
• In the Japanese movie Taiyou no Uta also known as Midnight Sun, the main character (Kaoru Amane)
• In the ITV series Ultraviolet, one of the humans is mistaken for a vampire because he avoids sunlight, when in fact he has XP.
• In the independent film Dark Side of the Sun (1988) with Brad Pitt as the main character suffering from XP.
• In the 2003 novel Second Glance by Jodi Picoult, Ethan Wakeman, the 9-year-old nephew of Ross Wakeman (the main protagonist)
• The 2003 Angela Johnson novel, A Cool Moonlight, centers on a girl who has XP and can never be in the sun. The family has gone to drastic measures to help make her life easier, and to make her feel like a normal 8-year-old.
• The 2011 film La permission de minuit by French director Delphine Gleize centers on a teenage boy with XP.

See also

• Biogerontology
• Cockayne syndrome
• Photophobia
• Senescence
• List of cutaneous conditions

References

1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0721629210.
2. ^ ^{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. 
3. ^ 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. 
4. ^ 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. PMC 2577106. PMID 18937855. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2577106. 

External links

Information

• GeneReviews/NCBI/NIH/UW entry on Xeroderma pigmentosum
• 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. PMC 2577106. PMID 18937855. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2577106. 

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