Summary about Disease
Xeroderma Pigmentosum Complementation Group G (XP-G) is a rare, autosomal recessive genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation from sunlight. Individuals with XP-G have a defective ERCC5 gene, which is critical for nucleotide excision repair (NER), a crucial DNA repair mechanism. This deficiency makes them unable to repair DNA damage caused by UV light, leading to a high risk of skin cancer, eye problems, and neurological abnormalities. XP-G is one of several complementation groups within XP, each resulting from mutations in different genes involved in the NER pathway.
Symptoms
Extreme sensitivity to sunlight (photosensitivity): Severe sunburn after minimal sun exposure.
Freckling and pigmentation changes: Development of numerous freckles at a young age, especially on sun-exposed areas.
Dry skin (xeroderma)
Premature aging of the skin (poikiloderma)
Skin cancer: High risk of developing basal cell carcinoma, squamous cell carcinoma, and melanoma at a young age.
Eye problems: Conjunctivitis, keratitis, corneal opacities, and increased risk of ocular tumors.
Neurological abnormalities: Progressive neurological deterioration may occur in some XP-G patients. This can include developmental delay, microcephaly, seizures, spasticity, ataxia, and cognitive impairment.
Causes
XP-G is caused by mutations in the ERCC5 gene (Excision Repair Cross-Complementation group 5). This gene provides instructions for making a protein that is essential for nucleotide excision repair (NER). NER is a DNA repair pathway that removes damaged DNA segments, including those caused by UV radiation. Mutations in ERCC5 impair NER, leading to the accumulation of DNA damage and the characteristic features of XP-G. The condition is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for their child to be affected.
Medicine Used
There is no cure for XP-G, and treatment focuses on managing symptoms and preventing complications.
Strict sun protection: Sunscreen with a high SPF, protective clothing (long sleeves, hats, sunglasses), and avoiding sun exposure during peak hours are crucial.
Topical medications: Creams for treating skin damage and precancerous lesions (e.g., topical chemotherapy like 5-fluorouracil or imiquimod).
Surgical removal of skin cancers: Early detection and removal of skin cancers are essential.
Artificial tears: To alleviate dry eyes.
Neurological management: Medications and therapies to manage neurological symptoms (e.g., anticonvulsants for seizures, physical therapy for spasticity).
Vitamin D supplementation: Because of sun avoidance, Vitamin D deficiency is common and requires supplementation.
Is Communicable
No, XP-G is not a communicable disease. It is a genetic disorder caused by inherited gene mutations and cannot be spread from person to person through any means.
Precautions
Rigorous sun protection: This is the most critical precaution.
Use broad-spectrum sunscreen with a high SPF (30 or higher) liberally and frequently, even on cloudy days.
Wear protective clothing: long sleeves, long pants, wide-brimmed hats, and UV-blocking sunglasses.
Avoid sun exposure as much as possible, especially between 10 AM and 4 PM.
Use UV-blocking window film on car and home windows.
Regular skin examinations: Frequent self-exams and professional skin exams by a dermatologist are necessary to detect skin cancers early.
Eye care: Regular eye exams by an ophthalmologist to monitor for and treat eye problems.
Neurological monitoring: Regular neurological evaluations to monitor for and manage neurological symptoms.
Genetic counseling: For families with a history of XP-G, genetic counseling can help assess the risk of having affected children.
How long does an outbreak last?
XP-G isn't characterized by "outbreaks." It is a chronic condition where sensitivity to sunlight persists throughout life. The DNA damage caused by UV radiation is cumulative and ongoing. Acute symptoms like sunburn can occur with even brief sun exposure, but the underlying condition is always present.
How is it diagnosed?
Clinical evaluation: Based on symptoms like extreme sun sensitivity, freckling, skin damage, and neurological abnormalities.
Skin biopsy: To examine skin tissue for characteristic changes and DNA damage.
Fibroblast culture: Cells from a skin biopsy are grown in a lab and tested for their ability to repair DNA damage after UV exposure. This is the definitive diagnostic test.
Complementation analysis: A laboratory test to determine the specific complementation group (e.g., group G) of XP.
Genetic testing: Molecular testing of the ERCC5 gene to identify specific mutations.
Timeline of Symptoms
Infancy/Early Childhood:
Extreme sensitivity to sunlight becomes apparent soon after birth or in early childhood.
Severe sunburns after minimal sun exposure.
Increased freckling and pigmentation changes on sun-exposed areas.
Childhood/Adolescence:
Dry skin (xeroderma) and premature aging of the skin (poikiloderma).
Development of skin cancers (basal cell carcinoma, squamous cell carcinoma, melanoma) at a young age.
Eye problems, such as conjunctivitis, keratitis, and corneal opacities.
Neurological symptoms may appear and progress over time in some individuals.
Adulthood:
Continued high risk of skin cancers and eye problems.
Progression of neurological abnormalities in affected individuals.
Overall shortened lifespan due to complications from skin cancers and neurological decline.
Important Considerations
Early diagnosis is crucial for implementing strict sun protection measures and minimizing DNA damage.
Multidisciplinary care is necessary, involving dermatologists, ophthalmologists, neurologists, and geneticists.
Psychological support: The chronic nature of the disease and the challenges it poses can lead to anxiety and depression. Psychological support and counseling can be helpful.
Research and clinical trials: Ongoing research aims to develop new therapies for XP-G, including gene therapy approaches.
Sun safety education: Educating affected individuals, families, and caregivers about the importance of sun protection is essential.
Family support networks: Connecting with other families affected by XP can provide valuable emotional support and practical advice.