Summary about Disease
Xeroderma pigmentosum complementation group F (XP-F) is a rare, inherited genetic disorder characterized by an extreme sensitivity to ultraviolet (UV) radiation from sunlight. Individuals with XP-F have a defective DNA repair mechanism, specifically within the nucleotide excision repair (NER) pathway. This defect prevents the body from effectively repairing DNA damage caused by UV exposure, leading to a significantly increased risk of sunburn, skin cancers, and neurological problems. The condition is caused by mutations in the ERCC4 gene.
Symptoms
Symptoms of XP-F typically appear in infancy or early childhood. Key symptoms include:
Extreme Sun Sensitivity: Severe sunburn after minimal sun exposure.
Skin Abnormalities: Freckling (especially in sun-exposed areas), dry skin (xeroderma), changes in skin pigmentation (hypopigmentation or hyperpigmentation).
Skin Cancers: High risk of developing various skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma, often at a young age.
Eye Problems: Sensitivity to light (photophobia), inflammation of the cornea (keratitis), clouding of the lens (cataracts), and tumors on the eyelids or surface of the eye.
Neurological Problems: In some cases, progressive neurological problems can occur, including developmental delays, intellectual disability, hearing loss, impaired coordination (ataxia), and spasticity.
Causes
XP-F is caused by mutations in the ERCC4 gene. This gene provides instructions for making a protein that is essential for the nucleotide excision repair (NER) pathway. The NER pathway repairs damaged DNA, including damage caused by UV radiation. Mutations in *ERCC4* disrupt the NER pathway, leading to an inability to repair UV-induced DNA damage effectively. XP-F is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene for their child to be affected.
Medicine Used
There is no cure for XP-F, and treatment focuses on managing symptoms and preventing complications.
Sunscreen: Broad-spectrum sunscreen with a high SPF is crucial and should be applied liberally and frequently.
Topical Medications: Creams and ointments may be used to treat dry skin and other skin conditions.
Chemotherapy Creams: Topical chemotherapy agents (e.g., 5-fluorouracil) may be used to treat precancerous skin lesions.
Surgery: Surgical removal of skin cancers is often necessary.
Other Cancer Treatments: Radiation therapy or chemotherapy may be used to treat advanced skin cancers.
Artificial Tears: To alleviate dry eye.
Vitamin D Supplementation: Because of limited sun exposure, vitamin D deficiency is common and may require supplementation.
Is Communicable
No, XP-F is not communicable. It is a genetic disorder caused by inherited gene mutations and cannot be spread from person to person.
Precautions
The most important precaution for individuals with XP-F is strict avoidance of sunlight and other sources of UV radiation. This includes:
Sun Protection:
Wearing protective clothing, such as long sleeves, long pants, wide-brimmed hats, and sunglasses.
Using high-SPF, broad-spectrum sunscreen on all exposed skin.
Avoiding outdoor activities during peak sunlight hours (10 AM to 4 PM).
Indoor Protection:
Using UV-filtering film on windows in homes and cars.
Avoiding tanning beds and sunlamps.
Regular Medical Checkups:
Routine skin exams to detect and treat skin cancers early.
Regular eye exams.
Neurological assessments to monitor for any neurological complications.
How long does an outbreak last?
XP-F is not characterized by outbreaks. It is a chronic, lifelong condition resulting from a genetic defect. The symptoms, such as sun sensitivity and skin abnormalities, are persistent and require ongoing management. Skin cancers can appear at any time.
How is it diagnosed?
XP-F is diagnosed based on a combination of factors:
Clinical Evaluation: Examination of the skin and eyes, and assessment of neurological function.
Family History: A family history of XP or similar symptoms.
Photosensitivity Testing: Evaluating the skin's sensitivity to UV radiation.
DNA Repair Assays: Laboratory tests to measure the ability of cells to repair UV-induced DNA damage. Skin cells or fibroblasts are cultured and their ability to repair DNA after UV exposure is assessed.
Genetic Testing: Genetic testing to identify mutations in the ERCC4 gene. This is the most definitive diagnostic method.
Timeline of Symptoms
Infancy/Early Childhood: Extreme sun sensitivity, severe sunburns after minimal sun exposure, freckling in sun-exposed areas.
Childhood/Adolescence: Development of dry skin, changes in skin pigmentation, early onset of skin cancers (often before age 10). Eye problems may begin.
Progressive: Neurological symptoms may develop at any point in life, but often progress over time, and can include developmental delays, intellectual disability, hearing loss, impaired coordination, and spasticity. The rate of neurological decline varies between individuals.
Lifelong: Continued risk of skin cancers and ongoing need for strict sun protection.
Important Considerations
Genetic Counseling: Genetic counseling is recommended for families with a history of XP-F to assess the risk of having affected children.
Psychological Support: The chronic nature of XP-F and the need for strict sun protection can be challenging. Psychological support and counseling can be beneficial for individuals with XP-F and their families.
Multidisciplinary Care: Management of XP-F requires a multidisciplinary team, including dermatologists, ophthalmologists, neurologists, and geneticists.
Early Diagnosis: Early diagnosis and intervention are crucial to minimizing the long-term complications of XP-F.
Awareness and Education: Raising awareness about XP-F among healthcare professionals and the general public is important for timely diagnosis and appropriate management.