Rare Hematology News

Disease Profile

Xeroderma pigmentosum

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

All ages

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ICD-10

Q82.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

XP; Xeroderma pigmentosa

Categories

Congenital and Genetic Diseases; Nervous System Diseases; Rare Cancers;

Summary

Xeroderma pigmentosum (XP) causes the skin and eyes to be extra sensitive to exposure to ultraviolet radiation from the sun and other sources. Symptoms begin in early childhood. People with XP can develop bad sunburns, blistering, and freckling in response to sunlight. The eyes may develop light sensitivity, corneal clouding, and swelling. Some people with XP have nervous system involvement as well. People with XP are at very high risk of developing skin cancer and other types of cancers. XP is caused by variants in one of at least nine genes involved in repairing damaged DNA. XP is inherited in an autosomal recessive pattern. Diagnosis is based on the clinical findings and specialized testing on skin cells. The diagnosis can be confirmed by the results of genetic testing. Treatment is focused on managing the symptoms. This includes avoiding sun exposure and performing frequent screenings for skin cancer and other cancers.[1][2][3]

Symptoms

The following list includes the most common signs and symptoms in people with xeroderma pigmentosum (XP). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Symptoms of XP may include:[1][2][3]

  • Skin and eyes extra sensitive to ultraviolet radiation
  • Severe sunburn with blistering
  • Patches of dark or light colored skin (hyperor hypopigmentation)
  • Dry skin and eyes
  • Corneal clouding
  • Corneal swelling
  • Microcephaly
  • Hearing loss
  • Progressive mental impairment

Symptoms of XP start in childhood. Many people with XP develop severe sunburns and blistering with minimal sun exposure. Others may have changes in skin coloring and texture. Sun exposure can also damage the eyes. About one-fourth of people with XP have neurological problems that may get worse over time. People with XP are at very high risk of developing skin cancer and other types of cancers. Most people with XP will get some type of cancer by early adulthood.[2][3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the dentition
Abnormal dentition
Abnormal teeth
Dental abnormality

[ more ]

0000164
Arthralgia
Joint pain
0002829
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Conjunctival telangiectasia
Small dilated blood vessels near membrane covering front of eye and eyelids
0000524
Cutaneous photosensitivity
Photosensitive skin
Photosensitive skin rashes
Photosensitivity
Sensitivity to sunlight
Skin photosensitivity
Sun sensitivity

[ more ]

0000992
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Dry skin
0000958
EEG abnormality
0002353
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Fatigue
Tired
Tiredness

[ more ]

0012378
Fever
0001945
Freckling
0001480
Hypogonadism
Decreased activity of gonads
0000135
Intellectual disability, progressive
Mental retardation, progressive
Progressive mental retardation

[ more ]

0006887
Optic atrophy
0000648
Poikiloderma
0001029
Telangiectasia of the skin
0100585
Thin skin
0000963
30%-79% of people have these symptoms
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Dermal atrophy
Skin degeneration
0004334
Erythema
0010783
Hyperkeratosis
0000962
Hypermelanotic macule
Hyperpigmented spots
0001034
Hypopigmented skin patches
Patchy loss of skin color
0001053
Keratitis
Corneal inflammation
0000491
Melanoma
0002861
Papilloma
0012740
Sensorineural hearing impairment
0000407
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
5%-29% of people have these symptoms
Abnormality of extrapyramidal motor function
0002071
Alopecia
Hair loss
0001596
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine

[ more ]

0003355
Ankyloblepharon
Adhesion of eyelids
Eyelids stuck together

[ more ]

0009755
Ataxia
0001251
Blepharitis
Inflammation of eyelids
0000498
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Craniofacial hyperostosis
Excessive bone growth of the skull and face
0004493
Decreased testicular size
Small testes
Small testis

[ more ]

0008734
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Ectropion
Eyelid turned out
0000656
Entropion
Eyelid turned in
0000621
Flat nasal alae
0010649
Melanocytic nevus
Beauty mark
0000995
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Neoplasm of the eye
Eye tumor
0100012
Opacification of the corneal stroma
0007759
Peripheral neuropathy
0009830
Photophobia
Extreme sensitivity of the eyes to light
Light hypersensitivity

[ more ]

0000613
Pterygium
0001059
Reduced tendon reflexes
0001315
Seizure
0001250
Short stature
Decreased body height
Small stature

[ more ]

0004322
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
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Cause

Xeroderma pigmentosum is caused by the DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, POLH, XPA, or XPC gene not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[1]

Diagnosis

Xeroderma pigmentosum (XP) is diagnosed based on the symptoms and clinical exam and may be confirmed by the results of genetic testing. Specialized testing may be done on skin cells to check for sensitivity to ultraviolet radiation.[2][3]

Treatment

Treatment for xeroderma pigmentosum (XP) is focused on managing the symptoms. People with XP are advised to avoid cigarette smoke, sunlight, and other forms of ultraviolet radiation exposure. In addition, people with XP may need regular screening for cancer, which may include a skin biopsy.[1] Clinical guidelines have been published for managing the symptoms of xeroderma pigmentosum.[4]

Specialists involved in the care of someone with XP may include:[1]

  • Dermatologist
  • Ophthalmologist
  • Oncologist
  • Neurologist
  • Audiologist
  • Otolaryngologist
  • Medical geneticist

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
    • Genetics Home Reference (GHR) contains information on Xeroderma pigmentosum. This website is maintained by the National Library of Medicine.
    • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.
    • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

      In-Depth Information

      • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
      • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Xeroderma pigmentosum. Click on the link to view a sample search on this topic.

        References

        1. Kraemer KH, DiGiovanna JJ. Xeroderma Pigmentosum. GeneReviews. Updated Sep 29, 2016; https://www.ncbi.nlm.nih.gov/books/NBK1397.
        2. Lucero R, Horowitz D. Xeroderma Pigmentosum. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Updated July 11, 2020; https://www.ncbi.nlm.nih.gov/books/NBK551563.
        3. Lehmann J, Seebode C, Martens MC, Emmert S. Xeroderma Pigmentosum Facts and Perspectives. Anticancer Res. Feb 2018; 38(2):1159-1164. https://pubmed.ncbi.nlm.nih.gov/29374753.
        4. Moriwaki S, Kanda F, Hayashi M, Yamashita D, Sakai Y, Nishigori C. Xeroderma pigmentosum clinical practice guidelines revision committee. Xeroderma pigmentosum clinical practice guidelines. J Dermatol. Oct, 2017; 44(10):1087-1096. https://pubmed.ncbi.nlm.nih.gov/28771907.
        5. Black JO. Xeroderma Pigmentosum. Head Neck Pathol. Jun 2016; 10(2):139-44. https://pubmed.ncbi.nlm.nih.gov/26975629.
        6. Walsh MF, Chang VY, Kohlmann WK, Scott HS, Cunniff C, at al. Recommendations for Childhood Cancer Screening and Surveillance in DNA Repair Disorders. Clin Cancer Res.. Jun 1, 2017; 23(11):e23-e31. https://pubmed.ncbi.nlm.nih.gov/28572264.

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