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Xeroderma pigmentosum, group E(XPE)

MedGen UID:
341219
Concept ID:
C1848411
Congenital Abnormality; Disease or Syndrome
Synonyms: DDB2-Related Xeroderma Pigmentosum; XERODERMA PIGMENTOSUM V; Xeroderma pigmentosum, complementation group E; Xeroderma pigmentosum, complementation group E, DDB-negative form; Xeroderma pigmentosum, group E, DDB-negative subtype; XP, GROUP E; XPE
SNOMED CT: Xeroderma pigmentosum group E (56048001); Xeroderma pigmentosum, group E (56048001)
 
Gene (location): DDB2 (11p11.2)
 
Monarch Initiative: MONDO:0010213
OMIM®: 278740

Disease characteristics

Excerpted from the GeneReview: Xeroderma Pigmentosum
Xeroderma pigmentosum (XP) is characterized by: Acute sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure) with marked freckle-like pigmentation of the face before age two years; Sunlight-induced ocular involvement (photophobia, severe keratitis, atrophy of the skin of the lids, ocular surface neoplasms); Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma) within the first decade of life. Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, progressive cognitive impairment, and ataxia). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years). [from GeneReviews]
Authors:
Kenneth H Kraemer  |  John J DiGiovanna  |  Deborah Tamura   view full author information

Additional descriptions

From NCBI curation
Xeroderma pigmentosum (XP) is characterized by: Sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure in ~60% of affected individuals, and marked freckle-like pigmentation of the face before age 2 years in most affected individuals); Ocular involvement (photophobia, keratitis, atrophy of the skin of the lids); and Greatly increased risk of cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma). Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, and progressive cognitive impairment). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years).
From MedlinePlus Genetics
Researchers have identified at least eight genetic forms of xeroderma pigmentosum: complementation group A (XP-A) through complementation group G (XP-G), plus a variant type (XP-V). The types are distinguished by their genetic cause. All of the types increase the risk of skin cancer, although some are more likely than others to be associated with neurological abnormalities.

Individuals with xeroderma pigmentosum may experience early menopause.

About 30 percent of people with xeroderma pigmentosum develop progressive neurological abnormalities in addition to problems involving the skin and eyes. These abnormalities can include hearing loss, poor coordination, difficulty walking, movement problems, loss of intellectual function, difficulty swallowing and talking, and seizures. When these neurological problems occur, they tend to worsen with time.

The eyes of people with xeroderma pigmentosum may be painfully sensitive to UVR (photophobia). If the eyes are not protected from UVR, they may become bloodshot and irritated, and the clear front covering of the eyes (the cornea) may become cloudy. In some people, the eyelashes fall out and the eyelids may be thin and turn abnormally inward or outward. In addition to an increased risk of cancer on the surface of the eye, xeroderma pigmentosum is associated with noncancerous growths on the eye. Many of these eye abnormalities can impair vision.

Without protection from the sun and other sources of UVR, most people with xeroderma pigmentosum develop multiple skin cancers during their lifetime. These cancers occur most often on  portions of the body that are exposed to the sun, including the face, the lips, the eyelids, the surface of the eyes, the scalp, and the tip of the tongue. Studies suggest that people with xeroderma pigmentosum may also have an increased risk of some internal cancers, including brain tumors, thyroid cancer, and blood cancers. Additionally, affected individuals who smoke cigarettes have a significantly increased risk of lung cancer.

People with xeroderma pigmentosum are 10,000 times more likely to develop non-melanoma skin cancer and up to 2,000 times more likely to  develop melanoma skin cancer compared to individuals without this condition. The types of skin cancer that can develop include basal cell carcinoma, squamous cell carcinoma, and melanoma. Most commonly, the first skin cancer appears in affected individuals before age 10. 

By age 2, almost all children with xeroderma pigmentosum develop freckling of the skin in sun-exposed areas (such as the face, arms, and lips); this type of freckling rarely occurs in young children without the disorder. In affected individuals, exposure to sunlight often causes dry skin (xeroderma) and changes in skin coloring (pigmentation). This combination of features gives the condition its name.

The signs of xeroderma pigmentosum usually appear in infancy or early childhood. About half of affected children develop a severe sunburn after spending just a few minutes in the sun. The sunburn causes redness and blistering that can last for weeks. However, some children with xeroderma pigmentosum can tan normally. 

Xeroderma pigmentosum, commonly known as XP, is an inherited condition characterized by an extreme sensitivity to ultraviolet radiation (UVR), which is present in sunlight and may also be found in some types of artificial lighting. This condition mostly affects the eyes and areas of skin exposed to the sun. Xeroderma pigmentosum is associated with an increased risk of UVR-induced cancers. People with this condition often experience premature aging. Some affected individuals also have problems involving the nervous system.  https://medlineplus.gov/genetics/condition/xeroderma-pigmentosum

Clinical features

From HPO
Melanoma
MedGen UID:
9944
Concept ID:
C0025202
Neoplastic Process
Melanoma is a type of skin cancer that begins in pigment-producing cells called melanocytes. This cancer typically occurs in areas that are only occasionally sun-exposed; tumors are most commonly found on the back in men and on the legs in women. Melanoma usually occurs on the skin (cutaneous melanoma), but in about 5 percent of cases it develops in melanocytes in other tissues, including the eyes (uveal melanoma) or mucous membranes that line the body's cavities, such as the moist lining of the mouth (mucosal melanoma). Melanoma can develop at any age, but it most frequently occurs in people in their fifties to seventies and is becoming more common in teenagers and young adults.\n\nMelanoma may develop from an existing mole or other normal skin growth that becomes cancerous (malignant); however, many melanomas are new growths. Melanomas often have ragged edges and an irregular shape. They can range from a few millimeters to several centimeters across. They can also be a variety of colors: brown, black, red, pink, blue, or white.\n\nA large number of moles or other pigmented skin growths on the body, generally more than 25, is associated with an increased risk of developing melanoma. Melanoma is also a common feature of genetic syndromes affecting the skin such as xeroderma pigmentosum. Additionally, individuals who have previously had melanoma are nearly nine times more likely than the general population to develop melanoma again. It is estimated that about 90 percent of individuals with melanoma survive at least 5 years after being diagnosed.\n\nMost melanomas affect only the outermost layer of skin (the epidermis). If a melanoma becomes thicker and involves multiple layers of skin, it can spread to other parts of the body (metastasize).
Squamous cell carcinoma of the skin
MedGen UID:
107512
Concept ID:
C0553723
Neoplastic Process
Squamous cell carcinoma of the skin is a malignant tumor of squamous epithelium.
Skin basal cell carcinoma
MedGen UID:
1648304
Concept ID:
C4721806
Neoplastic Process
The presence of a basal cell carcinoma of the skin.
Photophobia
MedGen UID:
43220
Concept ID:
C0085636
Sign or Symptom
Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.
Conjunctivitis
MedGen UID:
1093
Concept ID:
C0009763
Disease or Syndrome
Inflammation of the conjunctiva.
Keratitis
MedGen UID:
44013
Concept ID:
C0022568
Disease or Syndrome
Inflammation of the cornea.
Ectropion
MedGen UID:
4448
Concept ID:
C0013592
Disease or Syndrome
An outward turning (eversion) or rotation of the eyelid margin.
Entropion
MedGen UID:
41813
Concept ID:
C0014390
Disease or Syndrome
An abnormal inversion (turning inward) of the eyelid (usually the lower) towards the globe. Entropion is usually acquired as a result of involutional or cicatricial processes but may occasionally be congenital.
Telangiectasia
MedGen UID:
21088
Concept ID:
C0039446
Finding
Telangiectasias refer to small dilated blood vessels located near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. Telangiectasia are located especially on the tongue, lips, palate, fingers, face, conjunctiva, trunk, nail beds, and fingertips.
Dermal atrophy
MedGen UID:
101793
Concept ID:
C0151514
Disease or Syndrome
Partial or complete wasting (atrophy) of the skin.
Cutaneous photosensitivity
MedGen UID:
87601
Concept ID:
C0349506
Pathologic Function
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.
Poikiloderma
MedGen UID:
97905
Concept ID:
C0392777
Disease or Syndrome
Poikiloderma refers to a patch of skin with (1) reticulated hypopigmentation and hyperpigmentation, (2) wrinkling secondary to epidermal atrophy, and (3) telangiectasias.
Defective DNA repair after ultraviolet radiation damage
MedGen UID:
368469
Concept ID:
C1968564
Finding

Recent clinical studies

Etiology

de Souza Timoteo AR, Pinheiro de Almeida IC, Yurchenko AA, de Miranda Henriques SR, de Souza Segundo P, Rajabi F, Nikolaev S, Petta TB
BMC Med Genomics 2023 Aug 12;16(1):186. doi: 10.1186/s12920-023-01622-8. PMID: 37573316Free PMC Article
Karagün E, Eroz R, Gamsızkan M, Baysak S, Eyup Y, Ozcan Y
Int J Dermatol 2020 Aug;59(8):989-996. Epub 2020 Jun 12 doi: 10.1111/ijd.14957. PMID: 32530099
Yang R, Kong Q, Duan Y, Li W, Sang H
BMC Med Genet 2020 Mar 30;21(1):67. doi: 10.1186/s12881-020-00997-0. PMID: 32228487Free PMC Article
Itoh T
J Dermatol Sci 2006 Feb;41(2):87-96. Epub 2005 Dec 1 doi: 10.1016/j.jdermsci.2005.10.010. PMID: 16325378
Tan T, Chu G
Mol Cell Biol 2002 May;22(10):3247-54. doi: 10.1128/MCB.22.10.3247-3254.2002. PMID: 11971958Free PMC Article

Diagnosis

de Souza Timoteo AR, Pinheiro de Almeida IC, Yurchenko AA, de Miranda Henriques SR, de Souza Segundo P, Rajabi F, Nikolaev S, Petta TB
BMC Med Genomics 2023 Aug 12;16(1):186. doi: 10.1186/s12920-023-01622-8. PMID: 37573316Free PMC Article
Karagün E, Eroz R, Gamsızkan M, Baysak S, Eyup Y, Ozcan Y
Int J Dermatol 2020 Aug;59(8):989-996. Epub 2020 Jun 12 doi: 10.1111/ijd.14957. PMID: 32530099
Yang R, Kong Q, Duan Y, Li W, Sang H
BMC Med Genet 2020 Mar 30;21(1):67. doi: 10.1186/s12881-020-00997-0. PMID: 32228487Free PMC Article
Itoh T
J Dermatol Sci 2006 Feb;41(2):87-96. Epub 2005 Dec 1 doi: 10.1016/j.jdermsci.2005.10.010. PMID: 16325378
Tang JY, Hwang BJ, Ford JM, Hanawalt PC, Chu G
Mol Cell 2000 Apr;5(4):737-44. doi: 10.1016/s1097-2765(00)80252-x. PMID: 10882109Free PMC Article

Therapy

Ghodke H, Wang H, Hsieh CL, Woldemeskel S, Watkins SC, Rapić-Otrin V, Van Houten B
Proc Natl Acad Sci U S A 2014 May 6;111(18):E1862-71. Epub 2014 Apr 23 doi: 10.1073/pnas.1323856111. PMID: 24760829Free PMC Article
Tan T, Chu G
Mol Cell Biol 2002 May;22(10):3247-54. doi: 10.1128/MCB.22.10.3247-3254.2002. PMID: 11971958Free PMC Article
Tang JY, Hwang BJ, Ford JM, Hanawalt PC, Chu G
Mol Cell 2000 Apr;5(4):737-44. doi: 10.1016/s1097-2765(00)80252-x. PMID: 10882109Free PMC Article
Rapić Otrin V, Kuraoka I, Nardo T, McLenigan M, Eker AP, Stefanini M, Levine AS, Wood RD
Mol Cell Biol 1998 Jun;18(6):3182-90. doi: 10.1128/MCB.18.6.3182. PMID: 9584159Free PMC Article
Butel JS, Lee TH, Slagle BL
Princess Takamatsu Symp 1995;25:185-98. PMID: 8875624

Prognosis

Alexander H, Lee SK, Yu SL, Alexander S
Nucleic Acids Res 1996 Jun 15;24(12):2295-301. doi: 10.1093/nar/24.12.2295. PMID: 8710499Free PMC Article
Hwang BJ, Liao JC, Chu G
Mutat Res 1996 Jan 2;362(1):105-17. doi: 10.1016/0921-8777(95)00040-2. PMID: 8538642
Dualan R, Brody T, Keeney S, Nichols AF, Admon A, Linn S
Genomics 1995 Sep 1;29(1):62-9. doi: 10.1006/geno.1995.1215. PMID: 8530102

Clinical prediction guides

Ghodke H, Wang H, Hsieh CL, Woldemeskel S, Watkins SC, Rapić-Otrin V, Van Houten B
Proc Natl Acad Sci U S A 2014 May 6;111(18):E1862-71. Epub 2014 Apr 23 doi: 10.1073/pnas.1323856111. PMID: 24760829Free PMC Article
Roy N, Bommi PV, Bhat UG, Bhattacharjee S, Elangovan I, Li J, Patra KC, Kopanja D, Blunier A, Benya R, Bagchi S, Raychaudhuri P
Cancer Res 2013 Jun 15;73(12):3771-82. Epub 2013 Apr 22 doi: 10.1158/0008-5472.CAN-12-4069. PMID: 23610444Free PMC Article
Itoh T, Nichols A, Linn S
Oncogene 2001 Oct 25;20(48):7041-50. doi: 10.1038/sj.onc.1204909. PMID: 11704828
Kazantsev A, Bullock SK, Sancar A, Cordeiro-Stone M
Mutat Res 1998 Feb;407(1):55-65. doi: 10.1016/s0921-8777(97)00059-1. PMID: 9539981
Dualan R, Brody T, Keeney S, Nichols AF, Admon A, Linn S
Genomics 1995 Sep 1;29(1):62-9. doi: 10.1006/geno.1995.1215. PMID: 8530102

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