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Xeroderma pigmentosum, group G(XPG)

MedGen UID:
75657
Concept ID:
C0268141
Disease or Syndrome
Synonyms: ERCC5-Related Xeroderma Pigmentosum; Xeroderma pigmentosum complementation group G; Xeroderma pigmentosum type 7; Xeroderma pigmentosum VII; XP, GROUP G; XPG
SNOMED CT: Xeroderma pigmentosum group G (36454001); Xeroderma pigmentosum, group G (36454001)
 
Gene (location): ERCC5 (13q33.1)
 
Monarch Initiative: MONDO:0010216
OMIM®: 278780

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 OMIM
For a general description of xeroderma pigmentosum, see XPA (278700), and of Cockayne syndrome, see CSA (216400). Complementation group G has one of the smallest series of cases (Arlett et al., 1980).  http://www.omim.org/entry/278780
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
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Infantile spasms
MedGen UID:
854616
Concept ID:
C3887898
Disease or Syndrome
Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy).
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
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.
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Defective DNA repair after ultraviolet radiation damage
MedGen UID:
368469
Concept ID:
C1968564
Finding

Professional guidelines

PubMed

Xiang T, Kang X, Gong Z, Bai W, Chen C, Zhang W
Cancer Chemother Pharmacol 2017 Apr;79(4):791-800. Epub 2017 Mar 17 doi: 10.1007/s00280-017-3280-2. PMID: 28314991
Drury S, Boustred C, Tekman M, Stanescu H, Kleta R, Lench N, Chitty LS, Scott RH
Am J Med Genet A 2014 Jul;164A(7):1777-83. Epub 2014 Apr 3 doi: 10.1002/ajmg.a.36506. PMID: 24700531

Recent clinical studies

Etiology

Wang XQ, Terry PD, Li Y, Zhang Y, Kou WJ, Wang MX
World J Gastroenterol 2019 Sep 14;25(34):5152-5161. doi: 10.3748/wjg.v25.i34.5152. PMID: 31558863Free PMC Article
Zhang Z, Yin J, Xu Q, Shi J
J Clin Lab Anal 2018 Oct;32(8):e22564. Epub 2018 May 7 doi: 10.1002/jcla.22564. PMID: 29732643Free PMC Article
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Medicine (Baltimore) 2017 Aug;96(32):e7467. doi: 10.1097/MD.0000000000007467. PMID: 28796034Free PMC Article
Amr K, Messaoud O, El Darouti M, Abdelhak S, El-Kamah G
Gene 2014 Jan 1;533(1):52-6. Epub 2013 Oct 14 doi: 10.1016/j.gene.2013.09.125. PMID: 24135642
Messaoud O, Ben Rekaya M, Cherif W, Talmoudi F, Boussen H, Mokhtar I, Boubaker S, Amouri A, Abdelhak S, Zghal M
Int J Dermatol 2010 May;49(5):544-8. doi: 10.1111/j.1365-4632.2010.04421.x. PMID: 20534089

Diagnosis

Wang F, Zhang SD, Xu HM, Zhu JH, Hua RX, Xue WQ, Li XZ, Wang TM, He J, Jia WH
Oncotarget 2016 Mar 8;7(10):11724-32. doi: 10.18632/oncotarget.7352. PMID: 26887052Free PMC Article
Amr K, Messaoud O, El Darouti M, Abdelhak S, El-Kamah G
Gene 2014 Jan 1;533(1):52-6. Epub 2013 Oct 14 doi: 10.1016/j.gene.2013.09.125. PMID: 24135642
Messaoud O, Ben Rekaya M, Cherif W, Talmoudi F, Boussen H, Mokhtar I, Boubaker S, Amouri A, Abdelhak S, Zghal M
Int J Dermatol 2010 May;49(5):544-8. doi: 10.1111/j.1365-4632.2010.04421.x. PMID: 20534089
Lalle P, Nouspikel T, Constantinou A, Thorel F, Clarkson SG
J Invest Dermatol 2002 Feb;118(2):344-51. doi: 10.1046/j.0022-202x.2001.01673.x. PMID: 11841555
O'Donovan A, Wood RD
Nature 1993 May 13;363(6425):185-8. doi: 10.1038/363185a0. PMID: 8483505

Therapy

Kaur K, Kaur R
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Cancer 2011 Aug 1;117(15):3445-56. Epub 2011 Feb 1 doi: 10.1002/cncr.25925. PMID: 21287534

Prognosis

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Wang XQ, Terry PD, Li Y, Zhang Y, Kou WJ, Wang MX
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Xiang T, Kang X, Gong Z, Bai W, Chen C, Zhang W
Cancer Chemother Pharmacol 2017 Apr;79(4):791-800. Epub 2017 Mar 17 doi: 10.1007/s00280-017-3280-2. PMID: 28314991
Wang F, Zhang SD, Xu HM, Zhu JH, Hua RX, Xue WQ, Li XZ, Wang TM, He J, Jia WH
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Int J Clin Exp Pathol 2013;6(2):199-211. Epub 2013 Jan 15 PMID: 23330005Free PMC Article

Clinical prediction guides

Han C, Huang X, Hua R, Song S, Lyu L, Ta N, Zhu J, Zhang P
Medicine (Baltimore) 2017 Aug;96(32):e7467. doi: 10.1097/MD.0000000000007467. PMID: 28796034Free PMC Article
Xiang T, Kang X, Gong Z, Bai W, Chen C, Zhang W
Cancer Chemother Pharmacol 2017 Apr;79(4):791-800. Epub 2017 Mar 17 doi: 10.1007/s00280-017-3280-2. PMID: 28314991
Wang F, Zhang SD, Xu HM, Zhu JH, Hua RX, Xue WQ, Li XZ, Wang TM, He J, Jia WH
Oncotarget 2016 Mar 8;7(10):11724-32. doi: 10.18632/oncotarget.7352. PMID: 26887052Free PMC Article
Aracil M, Dauffenbach LM, Diez MM, Richeh R, Moneo V, Leal JF, Fernández LF, Kerfoot CA, Galmarini CM
Int J Clin Exp Pathol 2013;6(2):199-211. Epub 2013 Jan 15 PMID: 23330005Free PMC Article
Italiano A, Laurand A, Laroche A, Casali P, Sanfilippo R, Le Cesne A, Judson I, Blay JY, Ray-Coquard I, Bui B, Coindre JM, Nieto A, Tercero JC, Jimeno J, Robert J, Pourquier P
Cancer 2011 Aug 1;117(15):3445-56. Epub 2011 Feb 1 doi: 10.1002/cncr.25925. PMID: 21287534

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