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Xeroderma pigmentosum, group F(XPF)

MedGen UID:
120612
Concept ID:
C0268140
Congenital Abnormality
Synonyms: ERCC4-Related Xeroderma Pigmentosum; XERODERMA PIGMENTOSUM VI; XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP F; Xeroderma pigmentosum, type 6; XERODERMA PIGMENTOSUM, TYPE F; XP, GROUP F; XPF
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Xeroderma pigmentosum group F (42530008); Xeroderma pigmentosum, group F (42530008)
 
Gene (location): ERCC4 (16p13.12)
OMIM®: 278760

Disease characteristics

Excerpted from the GeneReview: Xeroderma Pigmentosum
Xeroderma pigmentosum (XP) is characterized by: Sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure in ~60% of affected individuals), with marked freckle-like pigmentation of the face before age two years in most affected individuals; Sunlight-induced ocular involvement (photophobia, keratitis, atrophy of the skin of the lids); Greatly increased risk of sunlight-induced 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 GeneReviews]
Authors:
Kenneth H Kraemer  |  John J DiGiovanna   view full author information

Additional descriptions

From OMIM
Xeroderma pigmentosum is an autosomal recessive disorder characterized by sun sensitivity and increased skin sensitivity to UV light, as well as an increased risk of skin cancer associated with a defect in nucleotide excision repair (NER). The XPF form of XP is usually relatively mild compared to other forms. Patients with XPF tend to have later onset of skin cancer. Some patients with XPF may develop neurologic impairment or growth defects, and are then classified as having Cockayne syndrome (summary by Kashiyama et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of xeroderma pigmentosa, see XPA (278700), and of Cockayne syndrome, see CSA (216400).  http://www.omim.org/entry/278760
From GHR
Xeroderma pigmentosum, which is commonly known as XP, is an inherited condition characterized by an extreme sensitivity to ultraviolet (UV) rays from sunlight. This condition mostly affects the eyes and areas of skin exposed to the sun. Some affected individuals also have problems involving the nervous system.The signs of xeroderma pigmentosum usually appear in infancy or early childhood. Many 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. Other affected children do not get sunburned with minimal sun exposure, but instead tan normally. 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, xeroderma pigmentosum.People with xeroderma pigmentosum have a greatly increased risk of developing skin cancer. Without sun protection, about half of children with this condition develop their first skin cancer by age 10. Most people with xeroderma pigmentosum develop multiple skin cancers during their lifetime. These cancers occur most often on the face, lips, and eyelids. Cancer can also develop on the scalp, in the eyes, and on the tip of the tongue. Studies suggest that people with xeroderma pigmentosum may also have an increased risk of other types of cancer, including brain tumors. Additionally, affected individuals who smoke cigarettes have a significantly increased risk of lung cancer.The eyes of people with xeroderma pigmentosum may be painfully sensitive to UV rays from the sun. If the eyes are not protected from the sun, 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 eye cancer, xeroderma pigmentosum is associated with noncancerous growths on the eye. Many of these eye abnormalities can impair vision.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.Researchers have identified at least eight inherited 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 skin cancer risk, although some are more likely than others to be associated with neurological abnormalities.  https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum

Clinical features

Astigmatism
MedGen UID:
2473
Concept ID:
C0004106
Disease or Syndrome
Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).
Deeply set eye
MedGen UID:
8638
Concept ID:
C0014306
Disease or Syndrome
An eye that is more deeply recessed into the plane of the face than is typical.
Congenital anomaly of eye
MedGen UID:
4623
Concept ID:
C0015393
Disease or Syndrome
Congenital absence of or defects in structures of the eye; may also be hereditary.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Neoplasm of the skin
MedGen UID:
40101
Concept ID:
C0007114
Neoplastic Process
Skin cancer is the most common form of cancer in the United States. The two most common types are basal cell cancer and squamous cell cancer. They usually form on the head, face, neck, hands, and arms. Another type of skin cancer, melanoma, is more dangerous but less common. . Anyone can get skin cancer, but it is more common in people who . - Spend a lot of time in the sun or have been sunburned. - Have light-colored skin, hair and eyes. - Have a family member with skin cancer. - Are over age 50. You should have your doctor check any suspicious skin markings and any changes in the way your skin looks. Treatment is more likely to work well when cancer is found early. If not treated, some types of skin cancer cells can spread to other tissues and organs. Treatments include surgery, radiation therapy, chemotherapy, photodynamic therapy (PDT), and biologic therapy. PDT uses a drug and a type of laser light to kill cancer cells. Biologic therapy boosts your body's own ability to fight cancer. NIH: National Cancer Institute.
Underweight
MedGen UID:
11989
Concept ID:
C0041667
Finding
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Height greater than two standard deviations below the mean of the appropriate reference population for the age and sex of the individual.
Hearing impairment
MedGen UID:
5453
Concept ID:
C0018772
Finding
A decreased magnitude of the sensory perception of sound.
Ataxia
MedGen UID:
849
Concept ID:
C0007758
Sign or Symptom
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- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
Tremors are unintentional trembling or shaking movements in one or more parts of your body. Most tremors occur in the hands. You can also have arm, head, face, vocal cord, trunk, and leg tremors. Tremors are most common in middle-aged and older people, but anyone can have them. The cause of tremors is a problem in the parts of the brain that control muscles in the body or in specific parts of the body, such as the hands. They commonly occur in otherwise healthy people. They may also be caused by problems such as. -Parkinson's disease. -Dystonia. -Multiple sclerosis. -Stroke. -Traumatic brain injury. -Alcohol abuse and withdrawal. -Certain medicines. Some forms are inherited and run in families. Others have no known cause. . There is no cure for most tremors. Treatment to relieve them depends on their cause. In many cases, medicines and sometimes surgical procedures can reduce or stop tremors and improve muscle control. Tremors are not life threatening. However, they can be embarrassing and make it hard to perform daily tasks. NIH: National Institute of Neurological Disorders and Stroke.
Brain atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
Dementia is the name for a group of symptoms caused by disorders that affect the brain. It is not a specific disease. People with dementia may not be able to think well enough to do normal activities, such as getting dressed or eating. They may lose their ability to solve problems or control their emotions. Their personalities may change. They may become agitated or see things that are not there. . Memory loss is a common symptom of dementia. However, memory loss by itself does not mean you have dementia. People with dementia have serious problems with two or more brain functions, such as memory and language. Although dementia is common in very elderly people, it is not part of normal aging. Many different diseases can cause dementia, including Alzheimer's disease and stroke. Drugs are available to treat some of these diseases. While these drugs cannot cure dementia or repair brain damage, they may improve symptoms or slow down the disease. NIH: National Institute of Neurological Disorders and Stroke.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28)
Flexion contracture
MedGen UID:
3227
Concept ID:
C0009917
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Defective DNA repair after ultraviolet radiation damage
MedGen UID:
368469
Concept ID:
C1968564
Finding
Flexion contracture
MedGen UID:
3227
Concept ID:
C0009917
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Scoliosis
MedGen UID:
21278
Concept ID:
C0037932
Finding
The presence of an abnormal lateral curvature of the spine.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Deeply set eye
MedGen UID:
8638
Concept ID:
C0014306
Disease or Syndrome
An eye that is more deeply recessed into the plane of the face than is typical.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Flexion contracture
MedGen UID:
3227
Concept ID:
C0009917
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Neoplasm of the skin
MedGen UID:
40101
Concept ID:
C0007114
Neoplastic Process
Skin cancer is the most common form of cancer in the United States. The two most common types are basal cell cancer and squamous cell cancer. They usually form on the head, face, neck, hands, and arms. Another type of skin cancer, melanoma, is more dangerous but less common. . Anyone can get skin cancer, but it is more common in people who . - Spend a lot of time in the sun or have been sunburned. - Have light-colored skin, hair and eyes. - Have a family member with skin cancer. - Are over age 50. You should have your doctor check any suspicious skin markings and any changes in the way your skin looks. Treatment is more likely to work well when cancer is found early. If not treated, some types of skin cancer cells can spread to other tissues and organs. Treatments include surgery, radiation therapy, chemotherapy, photodynamic therapy (PDT), and biologic therapy. PDT uses a drug and a type of laser light to kill cancer cells. Biologic therapy boosts your body's own ability to fight cancer. NIH: National Cancer Institute.
Papule
MedGen UID:
507324
Concept ID:
C0332563
Finding
A small, solid lesion, less than 1 cm in diameter, raised above the surface of the surrounding skin and hence palpable
Cutaneous photosensitivity
MedGen UID:
87601
Concept ID:
C0349506
Pathologic Function
increased sensitivity of the skin to light and other sources of UV
Numerous pigmented freckles
MedGen UID:
369801
Concept ID:
C1968565
Finding

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