Xeroderma pigmentosum

Xeroderma pigmentosum
Classification and external resources
An eight-year-old girl from Guatemala with xeroderma pigmentosum[1]
ICD-10	Q82.1
ICD-9	757.33
DiseasesDB	14198
MedlinePlus	001467
eMedicine	derm/462 neuro/399
MeSH	D014983

Child suffering from xeroderma pigmentosum in Rukum, Nepal

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.^[2]:574 In extreme cases, all exposure to sunlight must be forbidden, no matter how small; as such, individuals with the disease are often colloquially referred to as Children of the Night.^[3] 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^[4] 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 in the United States^[5] and a gene frequency of 1:200. XP is roughly six times more common in Japanese people^[4] 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.^[6] 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:

Symptoms

Symptoms include:

• Severe sunburn when exposed to only small amounts of sunlight. These often occur 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
• Limited growth of hair on chest and legs
• Scaly skin
• Dry skin
• Irregular dark spots on the skin
• Corneal ulcerations

Treatment

The most obvious, and often important part of treatment, is avoiding exposure to sunlight. Keratoses can also be treated using cryotherapy or fluorouracil.^[1]

Prognosis

Fewer than 40% of individuals with the disease survive beyond the age of 20. 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
• 1994 CBS-TV movie Children of the Dark is based on XP.
• Luke in the 2002 novel Going Out by Scarlett Thomas
• 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 2001 film The Others, the two children, Anne and Nicholas, suffer 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 Japanese drama "Taiyou no uta"(A Song to the Sun) centers around a girl with XP that dream of being a singer.
• The Spanish film "Eskalofrío" or "Shiver" released in 2008 featured a main character named Santi who is ostracized as he suffers from the condition.
• The 2011 film La permission de minuit by French director Delphine Gleize centers on a teenage boy with XP.
• The 2012 documentary "Sun Kissed" explores the XP problem on the Navajo Indian Reservation.

• The 2013 young adult novel What We Saw at Night by Jacquelyn Mitchard tells the story of three teenagers who are suffering from this disease, go out only when dark and witness something strange one night.
• The 2013 middle grade novel "Doom & Gloom" by M. J. Shaughnessy tells the story of a twelve-year-old boy who triumphs over his disease by donning a protective solar suit and becoming a superhero.

• Upcoming 2014 adult fiction book The Deepest Secret by Carla Buckley tells the story of a mother with a son who has XP and the lengths she will go to in order to protect him from a crisis that threatens to tear the community apart. ^[7]

See also

• Biogerontology
• Cockayne syndrome
• Photophobia
• Senescence
• List of cutaneous conditions
• List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer

References

External links

Information

• GeneReviews/NCBI/NIH/UW entry on xeroderma pigmentosum
• An article about this disorder from DigiLander.iol.it (in English and Italian)
• Cancer.Net Xeroderma Pigmentosum
• DermNet systemic/xeroderma-pigmentosum

Charities

• XP Society
• XP Family Support Group
• UK Patient Support Group

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