Summary about Disease
Xeroderma pigmentosum variant (XP-V), also known as XP-E, is a rare genetic disorder characterized by an increased sensitivity to ultraviolet (UV) radiation, primarily from sunlight. Unlike classical Xeroderma pigmentosum (XP), XP-V typically involves a milder form of the disease. Individuals with XP-V have a higher risk of developing skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma, at a younger age compared to the general population. Neurological abnormalities are usually absent or less severe in XP-V.
Symptoms
Severe sunburn after minimal sun exposure
Freckle-like spots (ephelides) appearing at a young age, particularly in sun-exposed areas
Dry, scaly skin (xeroderma)
Changes in skin pigmentation (hypo- or hyperpigmentation)
Increased risk of skin cancer (basal cell carcinoma, squamous cell carcinoma, melanoma)
Eye problems (less common and usually milder than in classical XP), such as photophobia (sensitivity to light) and conjunctivitis
Causes
XP-V is caused by mutations in the POLH gene. This gene provides instructions for making DNA polymerase eta (Polη), an enzyme involved in DNA repair. Polη is important for accurately replicating DNA when it has been damaged by UV radiation, specifically at sites of thymine dimers (a type of DNA damage). Mutations in *POLH* reduce or eliminate the function of Polη, impairing the ability to repair UV-induced DNA damage and leading to an accumulation of mutations, which increases the risk of skin cancer. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual must inherit two copies of the mutated gene (one from each parent) to have the disorder.
Medicine Used
There is no cure for XP-V; treatment focuses on managing symptoms and preventing complications, particularly skin cancer.
Sunscreen: Broad-spectrum sunscreen with a high SPF (30+) should be applied liberally and frequently to all exposed skin.
Topical medications: Creams and ointments may be used to treat dry skin and other skin conditions.
Surgical removal: Skin cancers are typically treated with surgical excision, Mohs surgery, or other appropriate methods depending on the type and location of the cancer.
Chemotherapy/Radiation: These may be needed to treat more aggressive skin cancers.
Vitamin D supplementation: Because strict sun avoidance can lead to vitamin D deficiency, supplementation may be recommended.
Is Communicable
No, XP-V is not communicable. It is a genetic disorder that is inherited, not contagious.
Precautions
Strict sun avoidance: Minimize exposure to sunlight, especially between 10 AM and 4 PM.
Protective clothing: Wear long sleeves, long pants, wide-brimmed hats, and sunglasses when outdoors.
UV-protective film: Apply UV-protective film to car and home windows.
Regular skin exams: Undergo regular skin exams by a dermatologist to detect skin cancers early.
Avoid tanning beds: Tanning beds emit UV radiation and should be strictly avoided.
Genetic counseling: Genetic counseling is recommended for individuals with a family history of XP-V.
How long does an outbreak last?
XP-V is not characterized by "outbreaks" in the traditional sense. It is a chronic condition that requires lifelong management. The symptoms, such as sun sensitivity and skin changes, are persistent and can worsen over time with continued sun exposure. Skin cancers can develop at any time and require prompt treatment.
How is it diagnosed?
Diagnosis of XP-V typically involves:
Clinical evaluation: Assessment of symptoms, including severe sunburn after minimal sun exposure, freckling, and dry skin.
Family history: Inquiry about a family history of XP or similar conditions.
Skin biopsy: Microscopic examination of skin tissue to look for characteristic changes associated with UV damage and potential skin cancer.
Genetic testing: Sequencing of the POLH gene to identify mutations that cause XP-V.
Cellular assays: Specialized laboratory tests that assess the ability of cells to repair UV-induced DNA damage
Timeline of Symptoms
Early childhood: Severe sunburns after minimal sun exposure, development of freckle-like spots (ephelides) on sun-exposed areas.
Childhood/Adolescence: Dry, scaly skin (xeroderma), changes in skin pigmentation.
Later in life (earlier than general population): Development of skin cancers (basal cell carcinoma, squamous cell carcinoma, melanoma). The age of onset varies but can be significantly younger than in individuals without XP-V.
Important Considerations
Early diagnosis is crucial: Early diagnosis and strict sun protection can significantly reduce the risk of skin cancer and improve quality of life.
Lifelong management is required: XP-V is a lifelong condition that requires ongoing monitoring and management.
Psychological support: Living with XP-V can be challenging, and psychological support may be helpful for individuals and families.
Multidisciplinary care: Management of XP-V often involves a team of specialists, including dermatologists, ophthalmologists, oncologists, and geneticists.
Awareness and education: Raising awareness about XP-V and educating affected individuals and families about sun protection and skin cancer prevention is essential.