Symptoms
Symptoms of XPG can vary widely in severity but typically include:
Extreme Sun Sensitivity: Severe sunburns with minimal sun exposure.
Skin Changes: Freckling, dry skin (xeroderma), patchy changes in skin color (pigmentation abnormalities).
Eye Problems: Sensitivity to light (photophobia), inflammation of the cornea (keratitis), clouding of the lens (cataracts).
Neurological Problems: Developmental delay, intellectual disability, microcephaly (small head size), seizures, progressive neurological degeneration.
Increased Cancer Risk: High incidence of skin cancers (basal cell carcinoma, squamous cell carcinoma, melanoma) even at a young age.
Other: Growth retardation, hearing loss.
Causes
XPG is caused by mutations in the ERCC5 gene. This gene provides instructions for making a protein involved in nucleotide excision repair (NER). NER is essential for repairing DNA damage caused by UV radiation and certain chemicals. Mutations in *ERCC5* impair NER, leading to the accumulation of DNA damage, particularly in skin cells exposed to sunlight and in neurons. It is inherited in an autosomal recessive manner, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
There is no cure for XPG. Treatment focuses on managing symptoms and preventing complications:
Sun Protection: Strict avoidance of sunlight, use of protective clothing (long sleeves, hats, sunglasses), and broad-spectrum sunscreen with a high SPF.
Monitoring for Skin Cancer: Regular skin examinations by a dermatologist.
Surgical Removal of Skin Cancers: Surgical excision, cryotherapy, or other treatments for skin cancers.
Treatment for Neurological Symptoms: Management of seizures with anticonvulsants, physical therapy, occupational therapy, and speech therapy to address developmental delays and motor impairments.
Eye Care: Artificial tears for dry eyes, treatment for keratitis or cataracts as needed.
Vitamin D Supplementation: To compensate for lack of sun exposure.
Retinoids/Chemotherapy: Topical or systemic medications may be used to manage precancerous skin lesions
Is Communicable
No, XPG is not communicable. It is a genetic disorder caused by inherited gene mutations, not by an infectious agent.
Precautions
The most important precaution is strict sun avoidance:
Minimize Sun Exposure: Stay indoors during peak sun hours (10 AM to 4 PM).
Protective Clothing: Wear long sleeves, pants, wide-brimmed hats, and UV-protective sunglasses when outdoors.
Sunscreen: Apply broad-spectrum sunscreen with an SPF of 30 or higher to all exposed skin, and reapply frequently, especially after swimming or sweating.
UV-Protective Film: Consider applying UV-protective film to windows in cars and homes.
Regular Medical Checkups: Regular skin exams by a dermatologist to detect skin cancers early. Neurological monitoring for progression of neurological symptoms.
How long does an outbreak last?
XPG isn't characterized by "outbreaks." Symptoms are chronic and progressive. There are no acute periods of illness followed by recovery. It's a lifelong condition requiring ongoing management. Severe sunburns can occur with even short periods of sun exposure.
How is it diagnosed?
Diagnosis of XPG typically involves:
Clinical Evaluation: Assessment of symptoms, including extreme sun sensitivity, skin changes, and neurological problems.
Family History: Review of family history for similar conditions.
Skin Biopsy: Examination of skin cells to look for characteristic DNA repair defects after UV exposure.
Genetic Testing: DNA sequencing of the ERCC5 gene to identify mutations.
Complementation Analysis: Functional studies to determine the specific XP complementation group.
Timeline of Symptoms
The timeline of symptoms can vary significantly among affected individuals, but generally follows this pattern:
Early Infancy/Childhood: Extreme sun sensitivity is usually apparent very early in life. Severe sunburns occur easily. Skin changes such as freckling and pigmentation abnormalities begin to appear.
Childhood/Adolescence: Neurological symptoms, if present, may become more apparent, including developmental delays, intellectual disability, and motor impairments. Skin cancers may begin to develop.
Adulthood: Skin cancers continue to develop, and neurological problems may progress. The severity and rate of progression of symptoms are highly variable.
Important Considerations
Genetic Counseling: Essential for families with a history of XPG to understand the risk of recurrence and to discuss reproductive options.
Early Diagnosis: Crucial for implementing protective measures and monitoring for complications.
Multidisciplinary Care: Management requires a team of specialists, including dermatologists, neurologists, ophthalmologists, and geneticists.
Psychosocial Support: Living with a chronic and debilitating condition can be challenging, and psychosocial support for patients and families is important.
Research: Ongoing research is aimed at developing new therapies for XPG, including gene therapy and other approaches to improve DNA repair.