View source for Xeroderma pigmentosum

{{infobox medical condition (new)
| name          = Xeroderma pigmentosum
| synonyms      = [[DeSanctis-Cacchione syndrome]]<ref name=GHR2018/><ref name=Derm2017/>

XP1 / XP2 / XP3 / XP4 / XP5 / XP6 / XP7<ref name="myriad1">{{Cite web |title=Not found |url=https://myriad.com/womens-health/2014/05/hello-world/ |url-status=dead |archive-url=https://web.archive.org/web/20221026171206/https://myriad.com/womens-health/2014/05/hello-world/ |archive-date=2022-10-26 |access-date=2023-03-06}}</ref>

Xeroderma pigmentosum I/II/III/IV/V/VI/VII<ref name="myriad1" />

Xeroderma pigmentosum complementation group A/B/C/D/E/F/G<ref name="myriad1" />

xeroderma pigmentosum group A/B/C/D/E/F/G<ref name="myriad1" />
| image         = Xeroderma pigmentosum 02.jpg
| field         = [[Medical genetics]]
| caption       = An eight-year-old girl from [[Guatemala]] with xeroderma pigmentosum<ref name="Halpern_2008" />
| symptoms      = Severe [[sunburn]] after only a few minutes in the sun, [[freckling]] in sun-exposed areas, dry skin, changes in skin pigmentation<ref name=GHR2018/>
| complications = [[Skin cancer]], [[brain cancer]], [[cataracts]]<ref name=GHR2018/>
| onset         = Becomes visible ~6 months of age<ref name="Derm2017">{{Cite web |title=Xeroderma pigmentosum |url=https://dermnetnz.org/topics/xeroderma-pigmentosum/ |access-date=25 February 2020 |website=dermnetnz.org}}</ref>
| duration      = Lifelong
| types         =
| causes        = [[Genetic disorder]] ([[autosomal recessive]])<ref name=GHR2018/>
| diagnosis     = Based on symptoms and confirmed by [[genetic testing]]<ref name=NORD2017/>
| differential  = [[Trichothiodystrophy]], [[Cockayne syndrome]], [[cerebrooculofacioskeletal syndrome]], [[erythropoietic protoporphyria]]<ref name=GARD2018/>
| prevention    = No cure available
| treatment     = Completely avoiding sun or UV rays, [[retinoid cream]]s, [[vitamin D]]<ref name=NORD2017/><ref name=GARD2018/>
| prognosis     = [[Life expectancy]] is shortened by about 30 years.<ref name=Ah2008/>
| frequency     = • 1 in 100,000 (worldwide)<ref name="myriad1" />

• 1 in 370 (India) {{cn|date=November 2023}}

• 1 in 22,000 (Japan)<ref name="myriad1" />

• 1 in 250,000 (US)<ref name=Leh2011/>

• 1 in 430,000 (Europe)

• 1 in 1,000,000 (UK)<ref name="myriad1" />
| deaths        =
| alt           =
}}
<!-- Definition and symptoms -->
'''Xeroderma pigmentosum''' ('''XP''') is a [[genetic disorder]] in which there is a decreased ability to repair [[DNA damage]] such as that caused by [[ultraviolet]] (UV) light.<ref name="GHR2018">{{Cite web |date=26 June 2018 |title=Xeroderma pigmentosum |url=https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum |access-date=28 June 2018 |website=Genetics Home Reference |publisher=U.S. Library of Medicine}}</ref> Symptoms may include a severe [[sunburn]] after only a few minutes in the sun, [[freckling]] in sun-exposed areas, [[dry skin]] and changes in skin pigmentation.<ref name=GHR2018/> Nervous system problems, such as [[hearing loss]], poor coordination, loss of intellectual function and [[seizures]], may also occur.<ref name=GHR2018/> Complications include a high risk of [[skin cancer]], with about half having skin cancer by age 10 without preventative efforts, and [[cataract]]s.<ref name=GHR2018/> There may be a higher risk of other cancers such as [[brain cancer]]s.<ref name=GHR2018/>

<!-- Cause and mechanism -->
XP is [[autosomal recessive]], with [[mutations]] in at least nine specific genes able to result in the condition.<ref name=GHR2018/><ref name="GARD2018">{{Cite web |date=2018 |title=Xeroderma pigmentosum |url=https://rarediseases.info.nih.gov/diseases/7910/xeroderma-pigmentosum |access-date=28 June 2018 |website=Genetic and Rare Diseases Information Center (GARD) |publisher=U.S. Department of Health and Human Services}}</ref> Normally, the damage to [[DNA]] which occurs in [[Epidermis (skin)|skin cells]] from exposure to UV light is repaired by [[nucleotide excision repair]].<ref name=GHR2018/> In people with xeroderma pigmentosum, this damage is not repaired.<ref name=GHR2018/> As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die.<ref name=GHR2018/> Diagnosis is typically suspected based on symptoms and confirmed by [[genetic testing]].<ref name=NORD2017/>

<!-- Treatment and prognosis -->
There is no cure for XP.<ref name=GARD2018/> Treatment involves completely avoiding the [[sun]].<ref name=GARD2018/> This includes protective clothing, [[sunscreen]] and dark sunglasses when out in the sun.<ref name=GARD2018/> [[Retinoid cream]]s may help decrease the risk of skin cancer.<ref name=GARD2018/> [[Vitamin D]] supplementation is generally required.<ref name=NORD2017/> If skin cancer occurs, it is treated in the usual way.<ref name=GARD2018/> The [[life expectancy]] of those with the condition is about 30 years less than normal.<ref name="Ah2008">{{Cite book |last=Ahmad |first=Shamim |url=https://books.google.com/books?id=_MPMriGtLbIC&pg=PA17 |title=Molecular Mechanisms of Xeroderma Pigmentosum |last2=Hanaoka |first2=Fumio |date=2008 |publisher=Springer Science & Business Media |isbn=9780387095998 |page=17 |language=en |name-list-style=vanc}}</ref>

<!-- Epidemiology, history and culture -->
The disease affects about 1 in 100,000 worldwide.<ref name="myriad1" /> By region, it affects about 1 in 370 in India, 1 in 20,000 in Japan, 1 in 250,000 people in the United States and 1 in 430,000 in Europe.<ref name="Leh2011">{{Cite journal |vauthors=Lehmann AR, McGibbon D, Stefanini M |date=November 2011 |title=Xeroderma pigmentosum |journal=Orphanet Journal of Rare Diseases |volume=6 |pages=70 |doi=10.1186/1750-1172-6-70 |pmc=3221642 |pmid=22044607 |doi-access=free}}</ref> It occurs equally commonly in males and females.<ref name=Gri2016/> Xeroderma pigmentosum was first described in the 1870s by [[Moritz Kaposi]].<ref name="NORD2017">{{Cite web |date=2017 |title=Xeroderma Pigmentosum |url=https://rarediseases.org/rare-diseases/xeroderma-pigmentosum/ |access-date=28 June 2018 |website=NORD (National Organization for Rare Disorders)}}</ref><ref name="Gri2016">{{Cite book |last=Griffiths |first=Christopher |url=https://books.google.com/books?id=85AvCgAAQBAJ&pg=RA9-PA41 |title=Rook's Textbook of Dermatology, 4 Volume Set |last2=Barker |first2=Jonathan |last3=Bleiker |first3=Tanya |last4=Chalmers |first4=Robert |last5=Creamer |first5=Daniel |date=2016 |publisher=John Wiley & Sons |isbn=9781118441190 |language=en |name-list-style=vanc}}</ref> In 1882, Kaposi coined the term ''xeroderma pigmentosum'' for the condition, referring to its characteristic dry, pigmented skin.<ref name=Gri2016/> Individuals with the disease have been referred to as "children of the night" or "moon children".<ref>{{Cite book |url=https://books.google.com/books?id=4d7wHD428MwC&pg=PT313 |title=Medical Biochemistry at a Glance |vauthors=Salway JG |date=2011 |publisher=John Wiley & Sons |isbn=9781118292402 |page=313 |language=en}}</ref>

== Signs and symptoms ==
[[File:Child suffering from Xeroderma Pigmentosum in Rukum,Nepal.jpg|thumb|Child with xeroderma pigmentosum in Nepal]]
[[File:Sequeira Plate 3.jpg|thumb|Girl with xeroderma pigmentosum showing [[epithelioma]]s on the eyelid and mouth]]
Signs and symptoms of xeroderma pigmentosum may include:{{citation needed|date=October 2020}}
* Severe [[sunburn]] when exposed to only small amounts of sunlight. These often occur during a child's first exposure to sunlight.
* Development of many [[freckle]]s at an early age
* Rough-surfaced growths ([[Actinic keratosis|solar keratose]]s), and [[skin cancer]]s
* Eyes that are painfully sensitive to the sun and may easily become irritated, [[Red eye (medicine)|bloodshot]] and clouded
* [[Blister]]ing 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
* [[Corneal ulcer]]ations

== Genetics ==
[[Image:autorecessive.svg|thumb|Xeroderma pigmentosum has an [[autosomal recessive]] pattern of inheritance.]]

One of the most frequent defects 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.<ref>{{Cite book |title=DNA repair and mutagenesis |vauthors=Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger T |publisher=ASM Press |year=2006 |isbn=978-1-55581-319-2 |location=Washington |page=1118}}</ref> If left unchecked, damage caused by ultraviolet light can cause mutations in individual cell's DNA. The causes of the neurological abnormalities are poorly understood and are not connected with exposure to ultraviolet light. The most current theories suggest that oxidative DNA damage is generated during normal metabolism in the central nervous system, and that some types of this damage must be repaired by NER.<ref name="Brooks_2008">{{Cite journal |vauthors=Brooks PJ |date=July 2008 |title=The 8,5'-cyclopurine-2'-deoxynucleosides: candidate neurodegenerative DNA lesions in xeroderma pigmentosum, and unique probes of transcription and nucleotide excision repair |journal=DNA Repair |volume=7 |issue=7 |pages=1168–79 |doi=10.1016/j.dnarep.2008.03.016 |pmc=2797313 |pmid=18495558}}</ref>

Since DNA repair is under genetic control, it can mutate. Many genetic disorders such as xeroderma pigmentosum (XP; MIM 278700) are caused by mutations in genes that repair damaged DNA. XP affects the mechanism that repairs UV damage in skin cell DNA. Those affected with the autosomal recessive disorder XP are extremely sensitive to UV light produced by the sun and develop pigmented spots, tumors, and skin cancer with minimal exposure. Individuals with XP are about 1,000 times more likely to develop skin cancer than individuals without the disorder.{{cn|date=October 2020}}

The molecular defects in XP cells result in a greatly elevated induction of mutations in sun-exposed skin of affected individuals. This increased mutation frequency probably accounts for the pigmentation changes and the skin cancers. Examination of mutations in the [[p53]] gene in tumors from XP patients reveal p53 mutations characteristic of UV exposure in the majority of tumors<ref name="Daya-Grosjean_2005">{{Cite journal |vauthors=Daya-Grosjean L, Sarasin A |date=April 2005 |title=The role of UV induced lesions in skin carcinogenesis: an overview of oncogene and tumor suppressor gene modifications in xeroderma pigmentosum skin tumors |journal=Mutation Research |volume=571 |issue=1–2 |pages=43–56 |bibcode=2005MRFMM.571...43D |doi=10.1016/j.mrfmmm.2004.11.013 |pmid=15748637}}</ref> As with all genetic disorders, genetic counseling and psychological support is appropriate for the families to discuss probability of occurrence in future pregnancies, feelings of isolation and concern about career prospects. There is no cure for xeroderma pigmentosum. The most common fate for individuals with XP is early death from cancer.  {{cn|date=October 2024}}

===XP repair proteins===

The [[XPA]] protein acts during NER as a scaffold for assembly of other [[DNA repair]] proteins at sites of [[DNA damage (naturally occurring)|DNA damage]] to ensure appropriate excision of the damage.<ref name="pmid27247238">{{Cite journal |vauthors=Sugitani N, Sivley RM, Perry KE, Capra JA, Chazin WJ |date=August 2016 |title=XPA: A key scaffold for human nucleotide excision repair |journal=DNA Repair |volume=44 |pages=123–135 |doi=10.1016/j.dnarep.2016.05.018 |pmc=4958585 |pmid=27247238}}</ref>

The [[XPB]] (ERCC3) protein is employed in unwinding the [[DNA]] double helix after DNA damage is initially recognized. [[Mutation]]s in the ''XPB(ERCC3)'' gene can lead to XP or XP combined with [[Cockayne syndrome]].<ref name="pmid16947863">{{Cite journal |vauthors=Oh KS, Khan SG, Jaspers NG, Raams A, Ueda T, Lehmann A, Friedmann PS, Emmert S, Gratchev A, Lachlan K, Lucassan A, Baker CC, Kraemer KH |date=November 2006 |title=Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome |journal=Human Mutation |volume=27 |issue=11 |pages=1092–103 |doi=10.1002/humu.20392 |pmid=16947863 |s2cid=22852219 |doi-access=free}}</ref>

The [[XPC (gene)|XPC]] protein forms a complex with [[RAD23B]] protein to form the initial damage recognition factor in global genomic [[nucleotide excision repair]] (GG-NER).<ref name="pmid9734359">{{Cite journal |vauthors=Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH |date=August 1998 |title=Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair |journal=Molecular Cell |volume=2 |issue=2 |pages=223–32 |doi=10.1016/s1097-2765(00)80132-x |pmid=9734359 |doi-access=free}}</ref> This complex recognizes a wide variety of damages that thermodynamically destabilize DNA duplexes.{{citation needed|date=October 2020}}

The XPD ([[ERCC2]]) protein, in combination with the XPB helicase-containing transcription/repair complex [[Transcription factor II H|TFIIH]], is employed in unwinding the DNA duplex after damage is initially recognized. Mutations in the ''XPD(ERCC2)'' gene cause a variety of syndromes; XP, [[trichothiodystrophy]] (TTD), or a combination of XP and Cockayne syndrome (XPCS).<ref name="pmid17172862">{{Cite journal |vauthors=Andressoo JO, Hoeijmakers JH, Mitchell JR |date=December 2006 |title=Nucleotide excision repair disorders and the balance between cancer and aging |journal=Cell Cycle |volume=5 |issue=24 |pages=2886–8 |doi=10.4161/cc.5.24.3565 |pmid=17172862 |s2cid=43682426|doi-access=free }}</ref><ref name="pmid23046824">{{Cite journal |vauthors=van de Ven M, Andressoo JO, van der Horst GT, Hoeijmakers JH, Mitchell JR |date=November 2012 |title=Effects of compound heterozygosity at the Xpd locus on cancer and ageing in mouse models |journal=DNA Repair |volume=11 |issue=11 |pages=874–83 |doi=10.1016/j.dnarep.2012.08.003 |pmid=23046824}}</ref> Both trichothiodystrophy and Cockayne syndrome display features of premature aging, suggesting an association between deficient DNA repair and premature aging .{{cn|date=October 2024}}

XPE is a heterodimeric protein composed of two subunits. The larger subunit [[DDB1]] primarily functions as a core component of [[CUL4A]]- and [[CUL4B]]-based E3 [[ubiquitin]] ligase complexes. Substrates that are ubiquitinnated by these complexes include proteins employed in DNA repair.<ref name="pmid21959250">{{Cite journal |vauthors=Iovine B, Iannella ML, Bevilacqua MA |date=December 2011 |title=Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions |journal=The International Journal of Biochemistry & Cell Biology |volume=43 |issue=12 |pages=1664–7 |doi=10.1016/j.biocel.2011.09.001 |pmid=21959250}}</ref>

The XPF ([[ERCC4]]) protein together with the [[ERCC1]] protein forms a complex usually designated ERCC1-XPF. This complex separates the DNA helix for a short distance on either side of the site of damage. It then acts as an [[endonuclease]] to incise the damaged DNA strand on the 5' side of the damaged site.<ref name="pmid8797827">{{Cite journal |vauthors=Sijbers AM, de Laat WL, Ariza RR, Biggerstaff M, Wei YF, Moggs JG, Carter KC, Shell BK, Evans E, de Jong MC, Rademakers S, de Rooij J, Jaspers NG, Hoeijmakers JH, Wood RD |date=September 1996 |title=Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease |journal=Cell |volume=86 |issue=5 |pages=811–22 |doi=10.1016/s0092-8674(00)80155-5 |pmid=8797827 |s2cid=12957716 |hdl-access=free |hdl=1765/3110}}</ref> Mutant cells with deficient ERCC1-XPF are not only defective in NER, but also in the repair of double-strand breaks and inter-strand crosslinks.{{cn|date=October 2024}}

The XPG protein is an endonuclease that incises DNA during NER at the 3' side of the damaged nucleotide. Mutations in the ''XPG ([[ERCC5]])'' gene can lead to XP alone, or in combination with Cockayne syndrome (CS), or in combination with infantile lethal cerebro-oculo-facio-skeletal syndrome.<ref name="pmid25299392">{{Cite journal |vauthors=Barnhoorn S, Uittenboogaard LM, Jaarsma D, Vermeij WP, Tresini M, Weymaere M, Menoni H, Brandt RM, de Waard MC, Botter SM, Sarker AH, Jaspers NG, van der Horst GT, Cooper PK, Hoeijmakers JH, van der Pluijm I |date=October 2014 |title=Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency |journal=PLOS Genetics |volume=10 |issue=10 |pages=e1004686 |doi=10.1371/journal.pgen.1004686 |pmc=4191938 |pmid=25299392 |doi-access=free}}</ref>

==Diagnosis==
===Types===
There are seven complementation groups, plus one variant form:
{| class="wikitable"
! Type || [[Diseases Database]] || [[OMIM]] || Gene || [[Locus (genetics)|Locus]] || Also known as / description
 |-
 |''Type A, I, XPA''||{{DiseasesDB|29877||none}}  || {{OMIM|278700||none}} || [[XPA]]   || 9q22.3  ||  Xeroderma pigmentosum group A - the classical form of XP
 |-
 |''Type B, II, XPB''|| {{DiseasesDB|29878||none}} ||  {{OMIM|133510||none}} || [[XPB]]    ||2q21|| Xeroderma pigmentosum group B
 |-
 |''Type C, III, XPC''|| {{DiseasesDB|29879||none}} || {{OMIM|278720||none}} || [[XPC (gene)|XPC]]   ||3p25||  Xeroderma pigmentosum group C
 |-
 |''Type D, IV, XPD''|| {{DiseasesDB|29880||none}} || {{OMIM|278730||none}} {{OMIM|278800||none}} || [[ERCC2|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''||  {{DiseasesDB|29881||none}} ||  {{OMIM|278740||none}} || [[DDB2]] || 11p12-p11 || Xeroderma pigmentosum group E
 |-
 |''Type F, VI, XPF''|| {{DiseasesDB|29882||none}} || {{OMIM|278760||none}} || [[ERCC4]]    || 16p13.3-p13.13 || Xeroderma pigmentosum group F
 |-
 |''Type G, VII, XPG''|| {{DiseasesDB|29883||none}} ||  {{OMIM|278780||none}} {{OMIM|133530||none}} || [[RAD2]] [[ERCC5]] || 13q33  || Xeroderma pigmentosum group G and COFS syndrome type 3
 |-
 |''Type V, XPV''|| || {{OMIM|278750||none}} || [[POLH]] || 6p21.1-p12 || Xeroderma pigmentosum variant - these patients have mutation in a gene that codes for a specialized DNA polymerase called [[DNA polymerase eta|polymerase-η (eta)]]. Polymerase-η can replicate over the damage and is needed when cells enter [[S-phase]] in the presence of a DNA-replication.
|}

== Treatment ==
[[Image:XP Child in UV-protective Clothing.jpg|thumb|Child in UV-protective clothing during initial stages of XP]]
There is no cure for the disorder; all treatment is symptomatic or preventive. Symptoms can be avoided or controlled by completely avoiding exposure to sunlight, either by staying indoors or wearing protective clothing and using [[sunscreen]] when outdoors.<ref>{{Cite book |last=Nussbaum |first=Robert |title=Genetics in Medicine |last2=McInnes |first2=Roderick |last3=Willard |first3=Huntington |date=2016-01-01 |publisher=Elsevier |isbn=978-14377-0696-3 |name-list-style=vanc}}</ref> [[Keratosis]] can also be treated by using [[cryotherapy]] or [[fluorouracil]].<ref name="Halpern_2008">{{Cite journal |vauthors=Halpern J, Hopping B, Brostoff JM |date=October 2008 |title=Photosensitivity, corneal scarring and developmental delay: Xeroderma Pigmentosum in a tropical country |journal=Cases Journal |volume=1 |issue=1 |pages=254 |doi=10.1186/1757-1626-1-254 |pmc=2577106 |pmid=18937855 |doi-access=free}}</ref> In more severe cases of XP, even minuscule amounts of UV light, for example, from covered windows or fluorescent bulbs, can be very dangerous and trigger symptoms.<ref>{{Cite magazine |date=September 24, 2014 |title=Xeroderma pigmentosum |url=https://www.indiatoday.in/lifestyle/health/story/story/xeroderma-pigmentosum/1/391127-300570-2014-09-24 |access-date=2020-07-05 |magazine=India Today |language=en}}</ref>

On September 10, 2020, Clinuvel Pharmaceuticals announced that it was investigating the use of its FDA-approved flagship drug [[Afamelanotide|Scenesse]] as a potential treatment to increase pain-free light exposure for patients with xeroderma pigmentosum.<ref>{{Cite web |title=SCENESSE® (afamelanotide 16mg) – Welcome to CLINUVEL |url=https://www.clinuvel.com/pharmaceutical/scenesse/scenesse |url-status=dead |archive-url=https://web.archive.org/web/20201020100319/https://www.clinuvel.com/pharmaceutical/scenesse/scenesse |archive-date=2020-10-20 |access-date=2020-09-24}}</ref><ref>{{Cite web |last=Commissioner |first=Office of the |date=2020-03-24 |title=FDA approves first treatment to increase pain-free light exposure in patients with a rare disorder |url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-increase-pain-free-light-exposure-patients-rare-disorder |access-date=2020-09-24 |website=FDA |language=en}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref><ref>{{Cite web |title=Scenesse (afamelanotide) for adults with a history of phototoxic reactions from EPP |url=https://scenesse.com/ |access-date=2020-09-24 |website=SCENESSE® (Afamelanotide) |language=en-US}}</ref>

== Prognosis ==
In the [[United States]], the probability for individuals with the disorder to survive until 40 years of age may be as high as 70% if they have never been exposed to sunlight in their life.<ref>{{Cite journal |last=Kraemer |first=Kenneth H. |date=1 February 1987 |title=Xeroderma Pigmentosum |url=https://jamanetwork.com/journals/jamadermatology/article-abstract/548003 |journal=Archives of Dermatology |volume=123 |issue=2 |pages=241 |doi=10.1001/archderm.1987.01660260111026 |access-date=21 June 2020|url-access=subscription }}</ref>

If a person is diagnosed early, does not have severe neurological symptoms, and takes precautionary measures to completely avoid any exposure to UV light and sunlight, they may be able to survive until middle age.{{cn|date=November 2023}}

==History==
Xeroderma pigmentosum was first described in 1874 by Hebra and [[Moritz Kaposi]]. In 1882, Kaposi coined the term xeroderma pigmentosum for the condition, referring to its characteristic dry, pigmented skin.{{citation needed|date=October 2020}}

The 1968 paper about XP by James Cleaver demonstrated the link between UV-induced DNA damage, faulty DNA repair and cancer.<ref name=":0" />

== Culture and society==
Because people with XP need to strictly avoid sunlight, but can go outside at night, they have been called ''children of the dark'', ''children of the night'', and ''vampire children''. These terms can be considered derogatory.<ref>{{Cite book |last=Almeida |first=Craig A. |url=https://books.google.com/books?id=j0RV27loexoC&pg=PT306 |title=Cancer: Basic Science and Clinical Aspects |last2=Barry |first2=Sheila A. |date=2011-08-26 |publisher=John Wiley & Sons |isbn=9781444357394 |language=en}}</ref>

XP has been a plot element in several fictional works. One of the common themes in films about XP is whether teens with XP will risk sun exposure in pursuit of a romantic partner.<ref>{{Cite news |last=Walsh |first=Katie |date=23 March 2018 |title=No spark in sick teen romance - Baltimore Sun |url=http://digitaledition.baltimoresun.com/tribune/article_popover.aspx?guid=7ae2bd5e-6b2d-405b-b7b2-baa51b206f34 |access-date=2018-07-08 |work=Baltimore Sun |agency=Tribune New Service}}</ref>

Film series like ''[[Children of Darkness (1921 film)|Children of Darkness]]'', a German silent-drama film which was released in two parts in the year of 1921 and 1922 respectively, were among some of the initially popular movies that were made about XP.{{cn|date=October 2024}}

Other films, like the 1964 American [[Drama (film and television)|drama film]] ''[[Della (film)|Della]]'', starring [[Joan Crawford]], [[Paul Burke (actor)|Paul Burke]], [[Charles Bickford]] and [[Diane Baker]], directed by [[Robert Gist]], which was originally produced by [[Four Star Television]] as a [[television pilot]] for a proposed [[NBC]] series named ''Royal Bay'', was also based on this [[skin disease]].{{cn|date=October 2024}}

''[[The Dark Side of the Sun (film)|The Dark Side of the Sun]]'', a 1988 American-Yugoslavian [[drama film]], was directed by Božidar Nikolić and stars [[Brad Pitt]] for his first ever leading role as a young man in search of a cure for his disorder.{{cn|date=October 2024}}

''[[The Others (2001 film)|The Others]]'', a 2001 American [[psychological horror]] film starring [[Nicole Kidman]], features two children, Anne and Nicholas, who must avoid all sunlight because of a rare disease characterized by [[photosensitivity]].{{cn|date=October 2024}}

A [[CBS]] [[television movie]] aired in 1994, ''Children of the Dark'', was based on the story of the real-life couple Jim and Kim Harrison, whose two daughters have XP.<ref>{{Cite web |last=Holder |first=Kathleen |name-list-style=vanc |date=1994-05-01 |title=Family in Twilight for Sun-Sensitive Girls : Health: Two daughters have a rare genetic intolerance that leaves victims vulnerable to skin cancers, blindness and neurological damage after exposure to sunlight |url=https://www.latimes.com/archives/la-xpm-1994-05-01-me-52495-story.html |access-date=2017-09-14 |publisher=[[Associated Press]]}}</ref><ref>{{Cite web |last=Voros |first=Drew |name-list-style=vanc |date=1994-04-15 |title=Review: 'Children of the Dark' |url=https://variety.com/1994/tv/reviews/children-of-the-dark-1200436702/ |access-date=2017-09-14 |publisher=[[Variety (magazine)|Variety]]}}</ref>

[[Lurlene McDaniel]]'s [[young adult book]] ''How I Do Love Thee'' features the story "Night Vision", in which the protagonist, [[leukemia]] survivor Brett, falls in love with a girl named Shayla that has XP.{{cn|date=October 2024}}

Christopher Snow, the protagonist of novelist [[Dean Koontz|Dean Koontz's]] ''[[Moonlight Bay Trilogy]]'', has XP and therefore must live most of his life during the night. The first two entries of the trilogy, ''[[Fear Nothing]]'' and ''[[Seize the Night (novel)|Seize the Night]]'', were both published in 1998. The final entry in the trilogy, tentatively titled ''[[Ride the Storm (novel)|Ride the Storm]]'', has yet to be published as of August 2020.<ref name="2018 Interview">[http://www.capradio.org/blogs/between-the-lines/2017/12/08/dean-koontz-takes-readers-on-a-techno-thriller-ride-in-his-new-jane-hawk-series 2017 Interview], capradio.org, 2017.</ref><ref>{{Cite web |title=Frequently Asked Questions |url=http://www.deankoontz.com/faq-categories/general-faq |url-status=dead |archive-url=https://web.archive.org/web/20180824135156/http://www.deankoontz.com/faq-categories/general-faq |archive-date=24 August 2018 |access-date=24 August 2018 |website=Dean Koontz}}</ref>

The 2011 [[France|French]] [[Drama (film and television)|drama film]] ''The Moon Child'' is based on a 13-year-old child with XP, which prevents him from exposing himself to daylight.

The 2012 documentary ''Sun Kissed'' explores the XP problem on the Navajo Indian Reservation, and links it to the [[Founder effect|genetic legacy]] of the [[Long Walk of the Navajo]], when the Navajo people were forced to move to a new location.<ref>{{Cite news |date=7 June 2012 |title=A Rare Genetic Disorder Is Stalking the Children of the Navajo Nation In POV's 'Sun Kissed,' Premiering Thursday, Oct. 18, 2012, on PBS |url=http://www.pbs.org/pov/blog/pressroom/2012/06/sun-kissed-premieres-on-pov/ |url-status=dead |archive-url=https://web.archive.org/web/20180629211242/http://www.pbs.org/pov/blog/pressroom/2012/06/sun-kissed-premieres-on-pov/ |archive-date=2018-06-29 |access-date=2018-06-29 |language=en-US}}</ref><ref>{{Cite news |last=Ziff |first=Deborah |name-list-style=vanc |title=Hiding From the Sun |url=https://www.abqjournal.com/159912/hiding-from-the-sun.html |access-date=2018-06-29 |work=The Albuquerque Journal |language=en-US}}</ref><ref>{{Cite news |last=Bender |first=Albert |name-list-style=vanc |date=2013-03-06 |title=Rare disease suddenly arises on Navajo Reservation |url=https://www.peoplesworld.org/article/rare-disease-suddenly-arises-on-navajo-reservation/ |access-date=2018-06-29 |work=People's World |language=en-US}}</ref>

The 2016 Vietnamese romance drama ''[[:vi:Khúc hát mặt trời|Khúc hát mặt trời]]'',  based on a 2006 Japanese film, ''[[A Song to the Sun]]'', tells the story of a girl named Yến Phương with XP and the impact of her sickness on her life and relationships, following the story of Phương's accidental exposure to sunlight and subsequent neurological degeneration.<ref>{{Citation |title=Khúc hát mặt trời |date=7 November 2015 |url=https://www.vov.vn/van-hoa/dien-anh/khuc-hat-mat-troi-chuyen-tinh-cam-dong-cua-nha-phuong-quang-tuan-448057.vov |access-date=2021-08-09 |language=vi}}</ref>

''[[Midnight Sun (2018 film)]]'' is a 2018 American romantic drama film based on the 2006 Japanese film A Song to the Sun. The film was directed by Scott Speer and written by Eric Kirsten, and stars Bella Thorne, Patrick Schwarzenegger, and Rob Riggle.{{cn|date=October 2024}}

== Research directions ==
Research into XP has had two main results: better understanding the disease itself, and also better understanding the normal biological mechanisms involved in DNA repair.<ref name=":0">{{Cite journal |vauthors=Kraemer KH, DiGiovanna JJ |date=March 2015 |title=Forty years of research on xeroderma pigmentosum at the US National Institutes of Health |journal=Photochemistry and Photobiology |volume=91 |issue=2 |pages=452–9 |doi=10.1111/php.12345 |pmc=4355260 |pmid=25220021}}</ref> Research into XP has produced insights that have been translated into treatments and prevention for cancer.<ref name=":0" />

== See also ==
* [[DeSanctis–Cacchione syndrome]]
* [[Genetic disorder]]
* [[Gerontology#Biogerontology|Biogerontology]]
* [[Cockayne syndrome]]
* [[List of skin conditions]]
* [[List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer]]
* [[Photophobia]]
* [[Senescence]]

== References ==
{{Reflist}}

== External links ==
{{Commons category}}
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=xp GeneReviews/NCBI/NIH/UW entry on xeroderma pigmentosum]

{{Medical resources
| DiseasesDB     = 14198
| ICD10          = {{ICD10|Q|82|1|q|80}}
| ICD9           = {{ICD9|757.33}}
| OMIM           =278700
| MedlinePlus    = 001467
| eMedicineSubj  = derm
| eMedicineTopic = 462
| eMedicine_mult = {{eMedicine2|neuro|399}}
| MeshID         = D014983
| GeneReviewsName=Xeroderma Pigmentosum
| GeneReviewsNBK=NBK1397
| Orphanet=910
}}

{{Congenital malformations and deformations of integument}}
{{DNA repair-deficiency disorder}}
{{Progeroid syndromes}}

{{Authority control}}

{{DEFAULTSORT:Xeroderma Pigmentosum}}
[[Category:Autosomal recessive disorders]]
[[Category:DNA replication and repair-deficiency disorders]]
[[Category:Genodermatoses]]
[[Category:Hereditary cancers]]
[[Category:Progeroid syndromes]]
[[Category:Rare diseases]]
[[Category:Wikipedia medicine articles ready to translate]]