Summary about Disease
Xeroderma pigmentosum complementation group F (XP-F) is a rare, autosomal recessive genetic disorder characterized by an extreme sensitivity to ultraviolet (UV) radiation from sunlight. This sensitivity leads to a significantly increased risk of developing skin cancers, ocular (eye) abnormalities, and, in some cases, neurological complications. XP-F is caused by a defect in the ERCC4 gene, which is responsible for nucleotide excision repair (NER), a crucial DNA repair pathway.
Symptoms
Extreme sensitivity to sunlight: Severe sunburn with blistering after minimal sun exposure.
Freckling: Extensive freckling in sun-exposed areas, appearing early in life.
Dry skin (xeroderma): Rough, scaly skin.
Pigmentary changes: Uneven skin pigmentation.
Skin cancers: High risk of basal cell carcinoma, squamous cell carcinoma, and melanoma, often appearing at a young age.
Ocular problems: Photophobia (sensitivity to light), conjunctivitis, corneal clouding, and increased risk of eye cancers.
Neurological problems (in some cases): Developmental delays, intellectual disability, seizures, hearing loss, and progressive neurological degeneration.
Causes
XP-F is caused by mutations in the ERCC4 gene. This gene provides instructions for making a protein that is essential for nucleotide excision repair (NER). NER is a DNA repair mechanism that removes damaged DNA segments, including those caused by UV radiation. When the *ERCC4* gene is mutated, the NER pathway is impaired, leading to an accumulation of DNA damage in cells exposed to UV light. This accumulated damage increases the risk of mutations that can lead to cancer and other problems. XP-F is inherited in an autosomal recessive manner, meaning that an affected individual must inherit two copies of the mutated gene (one from each parent).
Medicine Used
There is no cure for XP-F, and treatment focuses on managing symptoms and preventing further damage:
Sun protection: Strict avoidance of sunlight and UV radiation is crucial. This includes wearing protective clothing (long sleeves, hats, sunglasses), using broad-spectrum sunscreen with a high SPF (Sun Protection Factor), and staying indoors during peak sun hours.
Topical medications: Creams and ointments may be used to manage dry skin (emollients) and treat precancerous lesions (e.g., topical chemotherapy or immunotherapy).
Surgical removal: Skin cancers are typically treated with surgical excision. Mohs surgery may be used for more complex or recurrent cancers.
Chemotherapy/Radiation Therapy: These may be required for advanced skin cancers.
Ocular treatments: Artificial tears, ointments, or surgery may be necessary to manage eye problems.
Physical and occupational therapy: May be helpful for individuals with neurological problems.
Is Communicable
No, Xeroderma pigmentosum complementation group F (XP-F) is not communicable. It is a genetic disorder, meaning it is caused by a gene mutation and cannot be spread from person to person.
Precautions
The primary precaution for individuals with XP-F is strict avoidance of UV radiation:
Avoid sunlight: Stay indoors during peak sun hours (typically 10 a.m. to 4 p.m.).
Protective clothing: Wear long sleeves, long pants, wide-brimmed hats, and UV-protective sunglasses when outdoors.
Sunscreen: Apply broad-spectrum sunscreen with a high SPF (30 or higher) liberally and frequently, even on cloudy days.
UV-blocking window film: Install UV-blocking film on car and home windows.
Avoid tanning beds and sunlamps: These devices emit harmful UV radiation.
Regular skin exams: Undergo frequent skin exams by a dermatologist to detect and treat skin cancers early.
Genetic counseling: For families with a history of XP-F, genetic counseling can help assess the risk of having a child with the condition.
How long does an outbreak last?
XP-F is not characterized by "outbreaks." It is a chronic condition resulting from a genetic defect. Sensitivity to UV radiation is lifelong. Symptoms, such as sunburn or skin cancer development, may occur at any time with exposure to UV radiation.
How is it diagnosed?
Diagnosis of XP-F typically involves:
Clinical evaluation: Assessment of symptoms, including extreme sun sensitivity, freckling, and skin changes.
Family history: Inquiry about family history of XP or similar conditions.
Skin biopsy: Examination of a skin sample under a microscope to look for characteristic changes.
Cellular assays: Specialized laboratory tests, such as the measurement of unscheduled DNA synthesis (UDS) after UV exposure in cultured skin cells. These tests assess the ability of cells to repair DNA damage.
Genetic testing: Sequencing of the ERCC4 gene to identify mutations.
Timeline of Symptoms
Early infancy/childhood: Extreme sensitivity to sunlight, severe sunburn after minimal exposure, excessive freckling.
Childhood/adolescence: Dry skin, pigmentary changes, early development of skin cancers.
Adulthood: Continued risk of skin cancers, potential development of neurological problems (in some cases).
Important Considerations
Early diagnosis and intervention: Crucial to minimize UV exposure and prevent skin cancer.
Lifelong UV protection: Essential to reduce the risk of skin cancer and other complications.
Multidisciplinary care: Management often involves a team of specialists, including dermatologists, oncologists, ophthalmologists, and neurologists.
Psychological support: Living with XP-F can be challenging, and psychological support may be beneficial for individuals and their families.
Research: Ongoing research is focused on developing new therapies for XP-F, including gene therapy and other targeted approaches.