Summary about Disease
Xeroderma pigmentosum complementation group C (XP-C) is a rare, autosomal recessive genetic disorder characterized by an extreme sensitivity to ultraviolet (UV) radiation from sunlight. This sensitivity leads to a greatly increased risk of developing skin cancers, ocular (eye) abnormalities, and neurological problems. XP-C is caused by a mutation in the XPC gene, which plays a crucial role in nucleotide excision repair (NER), a DNA repair pathway that removes UV-induced DNA damage. The inability to properly repair this damage leads to the accumulation of mutations and the development of the characteristic features of XP-C. The severity and rate of progression of symptoms can vary significantly among affected individuals.
Symptoms
Extreme Sun Sensitivity: Severe sunburn after minimal sun exposure.
Freckling: Excessive freckling, especially in sun-exposed areas at a young age.
Dry Skin (Xeroderma): Abnormally dry and scaling skin.
Pigmentary Changes: Areas of skin with both increased (hyperpigmentation) and decreased (hypopigmentation) pigment.
Actinic Keratoses: Precancerous skin lesions that appear as rough, scaly patches.
Skin Cancers: High risk of developing basal cell carcinoma, squamous cell carcinoma, and melanoma at a young age.
Ocular Abnormalities: Sensitivity to light (photophobia), conjunctivitis, corneal clouding, and tumors on the surface of the eye.
Neurological Problems (Less Common): Progressive neurological degeneration can occur in some cases, leading to intellectual disability, microcephaly, seizures, and ataxia (problems with coordination).
Causes
XP-C is caused by mutations in the XPC gene, located on chromosome 3 (3p25.1). This gene provides instructions for making a protein that is involved in the nucleotide excision repair (NER) pathway. The *XPC* protein recognizes and binds to damaged DNA, initiating the repair process. Mutations in the *XPC* gene lead to a nonfunctional or deficient *XPC* protein, impairing the NER pathway and preventing the proper repair of UV-induced DNA damage. As a result, mutations accumulate in the skin cells, leading to the development of skin cancers and other symptoms. XP-C is inherited in an autosomal recessive pattern, meaning that an affected individual must inherit two copies of the mutated *XPC* gene (one from each parent) to develop the disorder. Individuals who inherit only one copy of the mutated gene are carriers and usually do not show symptoms of XP-C.
Medicine Used
There is no cure for XP-C, so treatment focuses on managing symptoms and preventing complications:
Strict Sun Protection: The most important aspect of management.
Sunscreen: Broad-spectrum sunscreen with a high SPF (30 or higher) should be applied liberally and frequently, even on cloudy days.
Protective Clothing: Wide-brimmed hats, sunglasses, and clothing that covers as much skin as possible.
Avoidance of Sunlight: Limit outdoor activities during peak sunlight hours.
Artificial Lighting: Using special filters on windows and fluorescent lights to reduce UV exposure indoors.
Regular Skin Examinations: Frequent skin examinations by a dermatologist to detect and treat precancerous and cancerous lesions early.
Treatment of Skin Cancers: Surgical removal, cryotherapy, topical medications (e.g., imiquimod), radiation therapy, or chemotherapy may be used to treat skin cancers.
Topical Medications: Topical retinoids or 5-fluorouracil cream may be used to treat actinic keratoses.
Eye Lubricants: Artificial tears can help alleviate dry eye symptoms.
Surgery: Surgical removal of tumors on the eye.
Antioxidant Supplements: Some studies suggest that antioxidant supplements may help reduce DNA damage, but more research is needed.
Is Communicable
No. XP-C is a genetic disorder and is not contagious or communicable. It cannot be spread from person to person through any means.
Precautions
Minimize Sun Exposure: Strict avoidance of sunlight is the most crucial precaution.
Use Broad-Spectrum Sunscreen: Apply sunscreen with an SPF of 30 or higher liberally and frequently, even on cloudy days.
Wear Protective Clothing: Wear wide-brimmed hats, sunglasses, and clothing that covers as much skin as possible.
UV Filters: Install UV-blocking filters on windows and fluorescent lights in homes and schools.
Regular Skin Exams: Undergo regular skin examinations by a dermatologist to detect skin cancers early.
Genetic Counseling: Genetic counseling is recommended for families with a history of XP-C to assess the risk of having affected children.
Education: Educate family members, teachers, and caregivers about the importance of sun protection and the need for early detection of skin cancers.
Monitor for Neurological Symptoms: If neurological problems develop, seek prompt medical attention and appropriate management.
How long does an outbreak last?
XP-C is not characterized by "outbreaks" in the traditional sense of an infectious disease. It is a chronic condition. The symptoms, such as sun sensitivity and skin changes, are persistent and lifelong. Skin cancers can develop at any time, particularly with continued sun exposure. Actinic keratoses can also persist and require ongoing monitoring and treatment.
How is it diagnosed?
Clinical Evaluation: Based on the individual's history of extreme sun sensitivity, characteristic skin findings (e.g., excessive freckling, pigmentary changes, dry skin), and early development of skin cancers.
Skin Biopsy: A skin biopsy may be performed to examine the cells for signs of UV damage and skin cancer.
Fibroblast Assay: Cultured skin cells (fibroblasts) are exposed to UV radiation, and their ability to repair DNA damage is measured. Reduced DNA repair capacity is indicative of XP. This can also help determine the specific complementation group.
Genetic Testing: Molecular genetic testing to identify mutations in the XPC gene can confirm the diagnosis.
Timeline of Symptoms
The timeline of symptoms in XP-C can vary among individuals, but a general progression is as follows:
Infancy/Early Childhood: Extreme sensitivity to sunlight, severe sunburns after minimal sun exposure, and excessive freckling in sun-exposed areas.
Childhood/Adolescence: Dry skin (xeroderma), pigmentary changes (hyperpigmentation and hypopigmentation), and the development of actinic keratoses.
Adolescence/Adulthood: Increased risk of developing skin cancers (basal cell carcinoma, squamous cell carcinoma, and melanoma) at a young age.
Throughout Life: Ocular abnormalities (photophobia, conjunctivitis, corneal clouding, and tumors on the surface of the eye) can develop at any age.
Variable: Neurological problems (intellectual disability, microcephaly, seizures, and ataxia) may develop in some individuals, often during childhood or adolescence, but can occur later in life as well.
Important Considerations
Early Diagnosis: Early diagnosis is crucial to implement strict sun protection measures and minimize the risk of skin cancer.
Lifelong Sun Protection: Sun protection is a lifelong commitment.
Regular Dermatological Care: Regular skin examinations by a dermatologist are essential for early detection and treatment of skin cancers.
Psychosocial Support: XP-C can have a significant impact on the affected individual's quality of life. Psychosocial support and counseling may be beneficial.
Family Support: Family members should be educated about XP-C and the importance of sun protection.
Research: Ongoing research is aimed at developing new treatments for XP-C, including gene therapy and targeted therapies.
Consider genetic testing: Carrier testing can be offered to at-risk relatives.
Association with other neurological conditions While less common, be vigilant for potential neurological decline.