Xeroderma pigmentosum (XP) is a
genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
in which there is a decreased ability to repair
DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
such as that caused by
ultraviolet
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nanometer, nm (with a corresponding frequency around 30 Hertz, PHz) to 400 nm (750 Hertz, THz), shorter than that of visible light, but longer than ...
(UV) light.
Symptoms may include a severe
sunburn
Sunburn is a form of radiation burn that affects living tissue, such as skin, that results from an overexposure to ultraviolet (UV) radiation, usually from the Sun. Common symptoms in humans and animals include: red or reddish skin that is ho ...
after only a few minutes in the sun,
freckling
Freckles are clusters of concentrated melaninized cells which are most easily visible on people with a fair complexion. Freckles do not have an increased number of the melanin-producing cells, or melanocytes, but instead have melanocytes that ...
in sun-exposed areas,
dry skin
Xeroderma, xerosis or xerosis cutis, or simply dry skin, is a skin condition characterized by excessively dry skin.
The medical term ''xeroderma'', meaning "dry skin", derives from modern Latin, ''xero-'' 'dry' + Greek ''derma'' 'skin'.
In most ...
and changes in skin pigmentation.
[ Nervous system problems, such as ]hearing loss
Hearing loss is a partial or total inability to Hearing, hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to Language ...
, poor coordination, loss of intellectual function and seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
, may also occur.[ Complications include a high risk of ]skin cancer
Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
, with about half having skin cancer by age 10 without preventative efforts, and cataracts
A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
.[ There may be a higher risk of other cancers such as ]brain cancer
A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and secondar ...
s.[
XP is ]autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
, with mutations
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
in at least nine specific genes able to result in the condition. Normally, the damage to DNA which occurs in skin cells
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different de ...
from exposure to UV light is repaired by nucleotide excision repair
Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucle ...
.[ In people with xeroderma pigmentosum, this damage is not repaired.][ As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die.][ Diagnosis is typically suspected based on symptoms and confirmed by ]genetic testing
Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
.[
There is no cure for XP.][ Treatment involves completely avoiding the ]sun
The Sun is the star at the center of the Solar System. It is a nearly perfect ball of hot plasma, heated to incandescence by nuclear fusion reactions in its core. The Sun radiates this energy mainly as light, ultraviolet, and infrared radi ...
.[ This includes protective clothing, ]sunscreen
Sunscreen, also known as sunblock or sun cream, is a photoprotective topical product for the skin that mainly absorbs, or to a much lesser extent reflects, some of the sun's ultraviolet (UV) radiation and thus helps protect against sunburn and ...
and dark sunglasses when out in the sun.[ ]Retinoid cream
The retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it. Retinoids have found use in medicine where they regulate epithelial cell growth.
Retinoids have many important functions throughout ...
s may help decrease the risk of skin cancer.[ ]Vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
supplementation is generally required.[ If skin cancer occurs, it is treated in the usual way.][ The ]life expectancy
Life expectancy is a statistical measure of the average time an organism is expected to live, based on the year of its birth, current age, and other demographic factors like sex. The most commonly used measure is life expectancy at birth ...
of those with the condition is about 30 years less than normal.
The disease affects about 1 in 100,000 worldwide. 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. It occurs equally commonly in males and females.[ Xeroderma pigmentosum was first described in the 1870s by ]Moritz Kaposi
Moritz Kaposi ( hu, Kaposi Mór, ; 23 October 1837 in Kaposvár, Hungary – 6 March 1902 in Vienna, Austria-Hungary) was a Hungarian physician and dermatologist who discovered the skin tumor that received his name (Kaposi's sarcoma).
Biography
...
. In 1882, Kaposi coined the term ''xeroderma pigmentosum'' for the condition, referring to its characteristic dry, pigmented skin.[ Individuals with the disease have been referred to as "children of the night" or "moon children".
]
Signs and symptoms
Signs and symptoms of xeroderma pigmentosum may include:
* Severe sunburn
Sunburn is a form of radiation burn that affects living tissue, such as skin, that results from an overexposure to ultraviolet (UV) radiation, usually from the Sun. Common symptoms in humans and animals include: red or reddish skin that is ho ...
when exposed to only small amounts of sunlight. These often occur during a child's first exposure to sunlight.
* Development of many freckle
Freckles are clusters of concentrated melaninized cells which are most easily visible on people with a fair complexion. Freckles do not have an increased number of the melanin-producing cells, or melanocytes, but instead have melanocytes that ...
s at an early age
* Rough-surfaced growths ( solar keratoses), and skin cancer
Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
s
* Eyes that are painfully sensitive to the sun and may easily become irritated, bloodshot and clouded
* Blister
A blister is a small pocket of body fluid (lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or infection. Most blisters are filled wi ...
ing or freckling on minimum sun exposure
* Telangiectasia
Telangiectasias, also known as spider veins, are small dilated blood vessels that can occur near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. These dilated blood vessels can develop anywhere on ...
(spider veins)
* Limited growth of hair on chest and legs
* Scaly skin
* Xeroderma
Xeroderma, xerosis or xerosis cutis, or simply dry skin, is a skin condition characterized by excessively dry skin.
The medical term ''xeroderma'', meaning "dry skin", derives from modern Latin, ''xero-'' 'dry' + Greek ''derma'' 'skin'.
In mos ...
(dry skin)
* Irregular dark spots on the skin
* Corneal ulcer
Corneal ulcer is an inflammatory or, more seriously, infective condition of the cornea involving disruption of its epithelial layer with involvement of the corneal Stroma of cornea, stroma. It is a common condition in humans particularly in the ...
ations
Genetics
One of the most frequent defects in xeroderma pigmentosum is an autosomal recessive genetic defect in which nucleotide excision repair
Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucle ...
(NER) enzymes are mutated, leading to a reduction in or elimination of NER. 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.
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.
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
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
gene in tumors from XP patients reveal p53 mutations characteristic of UV exposure in the majority of tumors 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.
XP repair proteins
The XPA
DNA repair protein complementing XP-A cells is a protein that in humans is encoded by the ''XPA'' gene. Function
Nucleotide excision repair (NER) is a major pathway for repairing a variety of bulky DNA damages including those introduced by UV i ...
protein acts during NER as a scaffold for assembly of other DNA repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...
proteins at sites of DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
to ensure appropriate excision of the damage.
The XPB
XPB (xeroderma pigmentosum type B) is an ATP-dependent DNA helicase in humans that is a part of the TFIIH transcription factor complex.
Structure
The 3D-structure of the archaeal homolog of XPB has been solved by X-ray crystallography by Dr. Jo ...
(ERCC3) protein is employed in unwinding the DNA double helix after DNA damage is initially recognized. Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s in the ''XPB(ERCC3)'' gene can lead to XP or XP combined with Cockayne syndrome
Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight (photosen ...
.
The XPC protein forms a complex with RAD23B
UV excision repair protein RAD23 homolog B is a protein that in humans is encoded by the ''RAD23B'' gene.
Function
The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in nucleotide ...
protein to form the initial damage recognition factor in global genomic nucleotide excision repair
Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucle ...
(GG-NER). This complex recognizes a wide variety of damages that thermodynamically destabilize DNA duplexes.
The XPD (ERCC2
__NOTOC__
ERCC2, or XPD is a protein involved in transcription-coupled nucleotide excision repair.
The XPD (ERCC2) gene encodes for a 2.3-kb mRNA containing 22 exons and 21 introns. The XPD protein contains 760 amino acids and is a polypeptide ...
) protein, in combination with the XPB helicase-containing transcription/repair complex TFIIH
Transcription factor II Human (transcription factor II H; TFIIH) is an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair (NER) pathways. TFIIH first came to light in 1989 ...
, 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
Trichothiodystrophy (TTD) is an autosomal recessive inherited disorder characterised by brittle hair and intellectual impairment. The word breaks down into ''tricho'' – "hair", '' thio'' – "sulphur", and ''dystrophy'' – "wasting away" or lit ...
(TTD), or a combination of XP and Cockayne syndrome (XPCS). Both trichothiodystrophy and Cockayne syndrome display features of premature aging, suggesting an association between deficient DNA repair and premature aging (see DNA damage theory of aging
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear ...
).
XPE is a heterodimeric protein composed of two subunits. The larger subunit DDB1
DNA damage-binding protein 1 is a protein that in humans is encoded by the ''DDB1'' gene.
Gene
The gene's position is on chromosome 11q12-q13.
Protein
The DDB1 gene encodes the large subunit of DNA damage-binding protein, a heterodimer composed ...
primarily functions as a core component of CUL4A
Cullin-4A is a protein that in humans is encoded by the ''CUL4A'' gene. CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates numerous key processes such as DNA repair, chro ...
- and CUL4B-based E3 ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
ligase complexes. Substrates that are ubiquitinnated by these complexes include proteins employed in DNA repair.
The XPF (ERCC4
ERCC4 is a protein designated as DNA repair endonuclease XPF that in humans is encoded by the ''ERCC4'' gene. Together with ERCC1, ERCC4 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.
The nuclease enzy ...
) protein together with the ERCC1
DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ''ERCC1'' gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.
Many aspects of these two gene ...
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
Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain. Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (without regard to sequence), while many, typically called restriction endonucleases ...
to incise the damaged DNA strand on the 5' side of the damaged site. 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.
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.
Diagnosis
Types
There are seven complementation groups, plus one variant form:
Treatment
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
Sunscreen, also known as sunblock or sun cream, is a photoprotective topical product for the skin that mainly absorbs, or to a much lesser extent reflects, some of the sun's ultraviolet (UV) radiation and thus helps protect against sunburn and ...
when outdoors. Keratosis
Keratosis (from '' kerat-'' + '' -osis'') is a growth of keratin on the skin or on mucous membranes stemming from keratinocytes, the prominent cell type in the epidermis. More specifically, it can refer to:
* actinic keratosis (also known as solar ...
can also be treated by using cryotherapy
Cryotherapy, sometimes known as cold therapy, is the local or general use of low temperatures in medical therapy. Cryotherapy may be used to treat a variety of tissue lesions. The most prominent use of the term refers to the surgical treatment, s ...
or fluorouracil
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pan ...
. 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.
On September 10, 2020, Clinuvel Pharmaceuticals announced that it was investigating the use of its FDA-approved flagship drug Scenesse as a potential treatment to increase pain-free light exposure for patients with xeroderma pigmentosum.
Prognosis
The average life expectancy
Life expectancy is a statistical measure of the average time an organism is expected to live, based on the year of its birth, current age, and other demographic factors like sex. The most commonly used measure is life expectancy at birth ...
of an individual with any type of XP and no neurological symptoms is approximately 37 years, and 29 years if neurological
Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...
symptoms are present.
In the United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
, 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.
In India
India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
, many patients with XP die at an early age from skin cancer
Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
s. However, 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.
History
Xeroderma pigmentosum was first described in 1874 by Hebra and Moritz Kaposi
Moritz Kaposi ( hu, Kaposi Mór, ; 23 October 1837 in Kaposvár, Hungary – 6 March 1902 in Vienna, Austria-Hungary) was a Hungarian physician and dermatologist who discovered the skin tumor that received his name (Kaposi's sarcoma).
Biography
...
. In 1882, Kaposi coined the term xeroderma pigmentosum for the condition, referring to its characteristic dry, pigmented skin.
The 1968 paper about XP by James Cleaver demonstrated the link between UV-induced DNA damage, faulty DNA repair and cancer.
Culture
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.
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.
Film series like ''Children of Darkness
''Children of Darkness'' is a 1983 American documentary film on PBS produced by Ara Chekmayan and Richard Kotuk. It was nominated for an Academy Award for Best Documentary Feature.
It is about mentally ill and emotionally troubled children an ...
'', a German silent-drama film which was released in two parts in the year of 1921 and 1922 respectively, was among some of the initially popular movies that was made about XP.
Other films, like the 1964 American drama film
In film and television, drama is a category or genre of narrative fiction (or semi-fiction) intended to be more serious than humorous in tone. Drama of this kind is usually qualified with additional terms that specify its particular super-g ...
'' Della'', starring Joan Crawford
Joan Crawford (born Lucille Fay LeSueur; March 23, ncertain year from 1904 to 1908was an American actress. She started her career as a dancer in traveling theatrical companies before debuting on Broadway. Crawford was signed to a motion pict ...
, Paul Burke, Charles Bickford
Charles Ambrose Bickford (January 1, 1891 – November 9, 1967) was an American actor known for supporting roles. He was nominated three times for the Academy Award for Best Supporting Actor, for '' The Song of Bernadette'' (1943), '' The ...
and Diane Baker
Diane Carol Baker is an American actress, producer and educator who has appeared in motion pictures and on television since 1959.
Early life
Baker was born in 1938 at Hollywood Presbyterian Hospital in Hollywood, Los Angeles, California a ...
, directed by Robert Gist
Robert Marion Gist (October 1, 1917 – May 21, 1998) was an American actor and film director.
Life and career
Gist was reared around the stockyards of Chicago, Illinois, during the Great Depression. Reform school-bound after injuring an ...
, which was originally produced by Four Star Television
Four Star Television, also called Four Star International, was an American television production company. Founded in 1952 as Four Star Productions by prominent Hollywood actors Dick Powell, David Niven, Charles Boyer, and Joel McCrea, it was insp ...
as a television pilot
A television pilot (also known as a pilot or a pilot episode and sometimes marketed as a tele-movie), in United States television, is a standalone episode of a television series that is used to sell a show to a television network or other distri ...
for a proposed NBC
The National Broadcasting Company (NBC) is an Television in the United States, American English-language Commercial broadcasting, commercial television network, broadcast television and radio network. The flagship property of the NBC Enterta ...
series named ''Royal Bay'', was also based on this skin disease
A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this sy ...
.
''The Dark Side of the Sun
''The'' () is a grammatical article in English, denoting persons or things already mentioned, under discussion, implied or otherwise presumed familiar to listeners, readers, or speakers. It is the definite article in English. ''The'' is the ...
'', a 1988 American-Yugoslavian drama film
In film and television, drama is a category or genre of narrative fiction (or semi-fiction) intended to be more serious than humorous in tone. Drama of this kind is usually qualified with additional terms that specify its particular super-g ...
, was directed by Božidar Nikolić and stars Brad Pitt
William Bradley Pitt (born December 18, 1963) is an American actor and film producer. He is the recipient of various accolades, including two Academy Awards, a British Academy Film Award, two Golden Globe Awards, and a Primetime Emmy Award. ...
for his first ever leading role as a young man in search of a cure for his disorder.
''The Others (2001 film)
''The Others'' ( es, Los otros) is a 2001 English-language Spanish gothic supernatural psychological horror film written, directed, and scored by Alejandro Amenábar. It stars Nicole Kidman, Fionnula Flanagan, Christopher Eccleston, Elaine Cassid ...
'', a 2001 American psychological horror
Psychological horror is a genre, subgenre of horror fiction, horror and psychological fiction with a particular focus on mental, emotional, and Mental state, psychological states to frighten, disturb, or unsettle its audience. The subgenre frequent ...
film starring Nicole Kidman
Nicole Mary Kidman (born 20 June 1967) is an American and Australian actress and producer. Known for her work across various film and television productions from several genres, she has consistently ranked among the world's highest-paid act ...
, features two children, Anne and Nicholas, who must avoid all sunlight because of a rare disease characterized by photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicity. ...
.
A CBS
CBS Broadcasting Inc., commonly shortened to CBS, the abbreviation of its former legal name Columbia Broadcasting System, is an American commercial broadcast television and radio network serving as the flagship property of the CBS Entertainm ...
television movie
A television film, alternatively known as a television movie, made-for-TV film/movie or TV film/movie, is a feature-length film that is produced and originally distributed by or to a television network, in contrast to theatrical films made for ...
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.
Lurlene McDaniel
Lurlene McDaniel (born 1944 in Philadelphia, Pennsylvania) is an American author who has written more than 70 young adult books. She is well known for writing about young adults struggling with mortality and chronic illness, a career that began ...
's young adult book
Young adult fiction (YA) is a category of fiction written for readers from 12 to 18 years of age. While the genre is primarily targeted at adolescents, approximately half of YA readers are adults.
The subject matter and genres of YA correlate ...
''How I Do Love Thee'' features the story "Night Vision", in which the protagonist, leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
survivor Brett, falls in love with a girl named Shayla that has XP.
Christopher Snow, the protagonist of novelist Dean Koontz's ''Moonlight Bay Trilogy
The ''Moonlight Bay Trilogy'' is an unfinished trilogy of three novels by Dean Koontz. They revolve around the mysterious events in Moonlight Bay, a fictitious Southern California town, that are investigated by the main character Christopher Snow ...
'', has XP and therefore must live most of his life during the night. The first two entries of the trilogy, ''Fear Nothing
''Fear Nothing'' is a novel released in 1998 by the best-selling author Dean Koontz. The book is the first installment in what is reported to be a three-part series of books, known as the Moonlight Bay Trilogy, featuring Christopher Snow, who ...
'' and ''Seize the Night
''Seize the Night'' is a novel written by the best-selling author Dean Koontz, released in 1998. The book is the second in a trilogy of books known as the Moonlight Bay Trilogy, involving Christopher Snow, who suffers from the rare (but real) dis ...
'', were both published in 1998. The final entry in the trilogy, tentatively titled '' Ride the Storm'', has yet to be published as of August 2020.[2017 Interview](_blank)
capradio.org, 2017.
The 2011 French drama film
In film and television, drama is a category or genre of narrative fiction (or semi-fiction) intended to be more serious than humorous in tone. Drama of this kind is usually qualified with additional terms that specify its particular super-g ...
''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 genetic legacy of the Long Walk of the Navajo
The Long Walk of the Navajo, also called the Long Walk to Bosque Redondo ( nv, Hwéeldi), was the 1864 deportation and attempted ethnic cleansing of the Navajo people by the United States federal government. Navajos were forced to walk from t ...
, when the Navajo people were forced to move to a new location.
The 2018 romance film ''Midnight Sun
The midnight sun is a natural phenomenon that occurs in the summer months in places north of the Arctic Circle or south of the Antarctic Circle, when the Sun remains visible at the local midnight. When the midnight sun is seen in the Arctic, t ...
'', based on a 2006 Japanese film, '' A Song to the Sun'', tells the story of a girl named Katie Price with XP and the impact of her sickness on her life and relationships, following the story of Price's accidental exposure to sunlight and subsequent neurological degeneration.
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. Research into XP has produced insights that have been translated into treatments and prevention for cancer.
See also
* DeSanctis–Cacchione syndrome
* Genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
* Biogerontology
Biogerontology is the sub-field of gerontology concerned with the biological aging process, its evolutionary origins, and potential means to intervene in the process. The term "biogerontology" was coined by S. Rattan, and came in regular use wit ...
* Cockayne syndrome
Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight (photosen ...
* List of cutaneous conditions
Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against t ...
*
* Photophobia
Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of ...
* Senescence
Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. The word ''senescence'' can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence inv ...
References
External links
GeneReviews/NCBI/NIH/UW entry on xeroderma pigmentosum
{{DEFAULTSORT:Xeroderma Pigmentosum
Autosomal recessive disorders
DNA replication and repair-deficiency disorders
Genodermatoses
Hereditary cancers
Progeroid syndromes
Rare diseases
Wikipedia medicine articles ready to translate