Summary about Disease
Xeroderma Pigmentosum Complementation Group D (XP-D) is a rare, autosomal recessive genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation from sunlight. This sensitivity leads to a high risk of developing skin cancers, neurological abnormalities in some cases, and, less commonly, internal cancers. XP-D is caused by mutations in the ERCC2 gene, which is involved in nucleotide excision repair (NER), a DNA repair mechanism that fixes damage caused by UV radiation. Individuals with XP-D lack sufficient NER capacity, making them highly susceptible to UV-induced DNA damage.
Symptoms
Symptoms of XP-D can vary in severity. Common symptoms include:
Extreme sun sensitivity: Severe sunburns after minimal sun exposure, often blistering.
Freckling: Excessive freckling in sun-exposed areas (face, neck, arms).
Dry skin (xeroderma): Scaly, dry skin that easily cracks or bleeds.
Pigmentary changes: Patches of hyperpigmentation (darkening) and hypopigmentation (lightening) of the skin.
Eye problems: Light sensitivity (photophobia), conjunctivitis, corneal clouding, and increased risk of eye cancers.
Skin cancers: High risk of developing basal cell carcinoma, squamous cell carcinoma, and melanoma at a young age.
Neurological abnormalities: Some individuals may develop progressive neurological problems, including developmental delays, intellectual disability, hearing loss, seizures, spasticity, and decreased reflexes.
Internal cancers: Increased risk, though less common than skin cancers.
Causes
XP-D is caused by mutations in the ERCC2 (also known as *XPD*) gene. This gene provides instructions for making a protein that is essential for the nucleotide excision repair (NER) pathway. NER is responsible for repairing DNA damage caused by UV radiation and other environmental factors. Mutations in *ERCC2* impair the NER pathway, leading to an accumulation of DNA damage in skin cells and other tissues. This accumulated damage increases the risk of mutations that can lead to cancer and other health problems. XP-D is inherited in an autosomal recessive pattern, 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-D. Treatment focuses on managing symptoms and preventing further damage. Key management strategies include:
Strict sun protection: This is the most important aspect of management. This includes:
Protective clothing: Long sleeves, pants, wide-brimmed hats, and UV-protective sunglasses.
Sunscreen: Broad-spectrum sunscreen with a high SPF (30 or higher) applied liberally and frequently, even on cloudy days.
Avoiding direct sunlight: Minimizing outdoor activities during peak sun hours (10 am to 4 pm).
Regular skin examinations: Frequent skin checks by a dermatologist to detect and treat skin cancers early.
Surgical removal of skin cancers: Prompt excision of any suspicious lesions.
Topical medications: Creams or ointments to treat precancerous lesions (e.g., 5-fluorouracil, imiquimod).
Eye protection and treatment: Lubricating eye drops, protective eyewear, and surgical intervention for corneal problems or eye cancers.
Management of neurological symptoms: Supportive care, physical therapy, and medications to manage seizures, spasticity, or other neurological complications.
Vitamin D supplementation: Due to limited sun exposure, individuals with XP-D may need vitamin D supplements to prevent deficiency.
Nicotinamide (Niacinamide): Shown in research to reduce the rate of new non-melanoma skin cancers in high-risk individuals
Is Communicable
No, XP-D is not communicable. It is a genetic disorder caused by inherited gene mutations and cannot be spread from person to person.
Precautions
Precautions for individuals with XP-D include:
Rigorous sun avoidance: This is paramount.
UV monitoring: Awareness of UV index levels and planning activities accordingly.
Sunscreen application: Regular and thorough application of broad-spectrum sunscreen.
Protective clothing: Consistent use of appropriate clothing and accessories.
Indoor UV protection: Using UV-filtering film on windows in homes and cars.
Careful lighting choices: Avoiding halogen and fluorescent lights, which can emit UV radiation. Use incandescent or LED lighting.
Regular medical follow-up: Routine checkups with a dermatologist, ophthalmologist, and neurologist (if neurological symptoms are present).
Genetic counseling: For families with a history of XP-D, genetic counseling can help assess the risk of having affected children.
How long does an outbreak last?
XP-D is not characterized by "outbreaks" in the traditional sense of an infectious disease. It is a chronic condition where the effects of UV exposure accumulate over time. Acute sunburns can occur after even brief sun exposure and can last for days to weeks. The long-term consequences, such as skin cancer development, are cumulative and can manifest over years or decades.
How is it diagnosed?
Diagnosis of XP-D typically involves:
Clinical evaluation: Assessment of symptoms, including extreme sun sensitivity, freckling, pigmentary changes, and skin cancers.
Family history: Determining if there is a family history of XP or similar conditions.
Skin biopsy: Examining a skin sample under a microscope to assess DNA repair capacity.
Genetic testing: Identifying mutations in the ERCC2 gene or other genes associated with XP.
Cellular assays: Specialized laboratory tests to measure the ability of cells to repair UV-induced DNA damage. These tests can involve culturing cells and measuring their ability to repair damage after UV irradiation.
Timeline of Symptoms
The timeline of symptoms can vary, but generally follows this pattern:
Infancy/Early Childhood:
Severe sunburns after minimal sun exposure.
Excessive freckling on sun-exposed areas.
Childhood/Adolescence:
Dry, scaly skin.
Pigmentary changes (hyperpigmentation and hypopigmentation).
Eye problems (photophobia, conjunctivitis).
Development of skin cancers (basal cell carcinoma, squamous cell carcinoma) may begin.
Adulthood:
Continued high risk of skin cancers.
Progression of pigmentary changes and skin damage.
Possible development of neurological abnormalities (if the subtype of XP-D is prone to neurological issues).
Increased risk of internal cancers (though less common).
Important Considerations
Early diagnosis is crucial: Early diagnosis and strict sun protection can significantly improve the prognosis for individuals with XP-D.
Multidisciplinary care: Management requires a team approach, including dermatologists, ophthalmologists, neurologists, geneticists, and other specialists.
Psychological support: Coping with XP-D can be challenging, and psychological support may be beneficial.
Education and advocacy: Raising awareness about XP-D is important for promoting early diagnosis and access to appropriate care.
Research participation: Participating in research studies can help advance understanding and treatment of XP-D.
Genetic counseling for family members: Siblings of affected individuals have a 25% chance of being affected and a 50% chance of being carriers of the mutated gene.
Awareness in school and daycare settings: Teachers and caregivers should be educated about the child's condition and the need for strict sun protection.