Summary about Disease
Xeroderma pigmentosum complementation group D (XP-D) is a rare, autosomal recessive genetic disorder characterized by an extreme sensitivity to ultraviolet (UV) light, leading to a significantly increased risk of skin cancers and other complications. It's one of several subtypes of Xeroderma Pigmentosum (XP), each linked to a specific gene involved in DNA repair. XP-D arises from mutations in the ERCC2 gene, which encodes a protein crucial for nucleotide excision repair (NER), a pathway vital for removing UV-induced DNA damage.
Symptoms
Extreme Sun Sensitivity: Severe sunburn with blistering after minimal sun exposure, often appearing in infancy.
Freckling and Pigmentary Changes: Numerous freckles at a young age, especially on sun-exposed areas (face, neck, arms). Uneven skin pigmentation (hypopigmentation and hyperpigmentation).
Dry Skin (Xeroderma): Scaly, dry skin.
Eye Problems: Sensitivity to light (photophobia), inflammation of the cornea (keratitis), clouding of the cornea, and an increased risk of eye cancers.
Skin Cancers: Significantly elevated risk of basal cell carcinoma, squamous cell carcinoma, and melanoma at a young age.
Neurological Abnormalities: In some cases, neurological problems such as intellectual disability, seizures, hearing loss, poor coordination (ataxia), and developmental delays can occur. This is more common in severe forms of XP-D.
Progressive Neurological Degeneration: Some individuals with XP-D may experience progressive neurological decline.
Causes
XP-D is caused by mutations in the ERCC2 gene (also known as *XPD*). This gene provides instructions for making a protein that is part of the TFIIH complex. TFIIH is involved in DNA transcription and nucleotide excision repair (NER). NER is a crucial DNA repair mechanism that removes bulky DNA damage, including that caused by UV radiation. Mutations in *ERCC2* impair the NER pathway, leading to an accumulation of UV-induced DNA damage. This accumulated damage results in the signs and symptoms of XP-D. 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-D; treatment focuses on managing symptoms and preventing complications.
Sunscreen: Broad-spectrum sunscreen with a high SPF (30 or higher) is crucial and should be applied liberally and frequently to all exposed skin.
Topical Medications: Topical chemotherapy (e.g., 5-fluorouracil cream) may be used to treat precancerous skin lesions (actinic keratoses). Imiquimod cream may also be used.
Surgery: Surgical removal of skin cancers is often necessary. Mohs surgery is a specialized technique that may be used for precise removal of skin cancers.
Retinoids: Oral retinoids (e.g., acitretin) may be used to reduce the risk of developing new skin cancers, but they have potential side effects.
Lubricants: Artificial tears and lubricating ointments help manage dry eye symptoms.
Supplements: Vitamin D supplementation may be necessary if sun avoidance leads to deficiency.
Chemotherapy/Radiation: For more advanced cases of skin cancer.
Is Communicable
No, XP-D is not communicable. It is a genetic disorder caused by inherited gene mutations, not by an infectious agent.
Precautions
Strict Sun Avoidance: This is the most critical precaution. Avoid direct sunlight, especially between 10 AM and 4 PM.
Protective Clothing: Wear long sleeves, long pants, wide-brimmed hats, and UV-protective sunglasses when outdoors.
UV-Protective Window Film: Apply UV-protective film to windows in homes and cars.
Regular Skin Exams: Undergo frequent skin examinations by a dermatologist to detect and treat skin cancers early.
Eye Protection: Protect eyes with UV-blocking sunglasses and seek regular eye exams.
Genetic Counseling: Families with a history of XP-D should consider genetic counseling to understand the risk of having affected children.
Indoor Activities: Maximize time spent indoors during daylight hours.
Awareness: Educate family, friends, and school personnel about the condition and the need for sun protection.
How long does an outbreak last?
XP-D is not characterized by "outbreaks." It is a chronic condition resulting from a genetic defect. The effects of the disease, such as sun sensitivity and the development of skin cancers, are ongoing and require continuous management. Individual skin cancers or precancerous lesions may "appear," and these can be treated (e.g., removed surgically).
How is it diagnosed?
Clinical Evaluation: Based on symptoms, especially extreme sun sensitivity and early development of freckles and skin lesions.
Skin Biopsy: A skin biopsy can show characteristic DNA damage and abnormalities.
Genetic Testing: Genetic testing to identify mutations in the ERCC2 gene confirms the diagnosis.
Cellular Assays: Specialized laboratory tests can measure the ability of cells to repair UV-induced DNA damage. (e.g., measuring unscheduled DNA synthesis (UDS))
Prenatal Testing: Available for families with a known history of XP-D to determine if a fetus is affected.
Timeline of Symptoms
Infancy: Severe sunburns after minimal sun exposure, even with typical sun protection measures.
Early Childhood: Appearance of numerous freckles, especially on sun-exposed areas. Dry, scaly skin. Photophobia.
Childhood/Adolescence: Development of actinic keratoses (precancerous skin lesions).
Adulthood (Often Earlier): Increased risk of skin cancers (basal cell carcinoma, squamous cell carcinoma, melanoma).
Variable: Neurological symptoms (if present) may appear in early childhood or later in life, and can progressively worsen.
Important Considerations
Lifelong Management: XP-D requires lifelong, comprehensive management, including strict sun protection, regular medical follow-up, and proactive monitoring for skin cancers.
Multidisciplinary Care: Care should be coordinated by a team of specialists, including dermatologists, ophthalmologists, neurologists, and geneticists.
Psychosocial Support: The condition can have a significant impact on quality of life, and psychosocial support for individuals and families is important.
Neurological Involvement: Be aware that not all individuals with XP-D have neurological problems, but those who do often have a more severe prognosis.
Cancer Prevention: While XP-D greatly increases cancer risk, vigilance and proactive management can significantly improve outcomes.
New Therapies: Research is ongoing to develop new therapies for XP-D, including gene therapy and drugs that enhance DNA repair.