Summary about Disease
Xeroderma Pigmentosum Complementation Group B (XP-B) is a rare, inherited autosomal recessive genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation. It falls under the broader category of Xeroderma Pigmentosum (XP) but is often more severe. XP-B is caused by mutations in the ERCC3 gene, which is crucial for DNA repair, specifically nucleotide excision repair (NER). Individuals with XP-B have a significantly increased risk of developing skin cancers, neurological problems, and premature aging. XP-B is associated with a combined XP/Cockayne syndrome (CS) phenotype.
Symptoms
Symptoms of XP-B are generally more severe and appear earlier in life than in other forms of XP. These may include:
Extreme sun sensitivity: Severe sunburn with blistering after minimal sun exposure.
Progressive skin damage: Freckling, irregular pigmentation, and thinning of the skin (poikiloderma).
Increased skin cancer risk: Early onset of basal cell carcinoma, squamous cell carcinoma, and melanoma.
Ocular problems: Sensitivity to light (photophobia), conjunctivitis, keratitis, and potential blindness.
Neurological abnormalities: Developmental delays, intellectual disability, progressive neurological degeneration, microcephaly, seizures, and ataxia.
Growth Deficiency: Failure to thrive
Causes
XP-B is caused by mutations in the ERCC3 (Excision Repair Cross-Complementation group 3) gene, also known as XPB. This gene provides instructions for making a protein that is part of the TFIIH complex, which is essential for nucleotide excision repair (NER). NER is a critical DNA repair pathway that removes damaged DNA, including UV-induced damage. Mutations in *ERCC3* impair the NER pathway, leading to an inability to repair UV-induced DNA damage. The defective DNA repair results in the accumulation of mutations, causing the characteristic symptoms of XP-B. It is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
There is no cure for XP-B, and treatment focuses on managing symptoms and preventing further damage:
Strict sun protection: High SPF sunscreens, protective clothing, wide-brimmed hats, and UV-protective sunglasses are essential.
Regular dermatological exams: Frequent skin examinations for early detection and treatment of skin cancers.
Surgical removal of skin cancers: Excision, cryotherapy, or other methods to remove cancerous lesions.
Topical medications: Creams like 5-fluorouracil or imiquimod may be used for some precancerous lesions.
Supportive therapies: Management of neurological symptoms, such as physical therapy, occupational therapy, and speech therapy.
Vitamin D supplementation: Due to sun avoidance, vitamin D deficiency is common.
Retinoids: May be used to treat actinic keratoses and potentially reduce skin cancer risk (use with caution and under strict medical supervision).
Is Communicable
XP-B is not communicable. It is a genetic disorder caused by inherited gene mutations, not by an infectious agent.
Precautions
Precautions for individuals with XP-B focus on minimizing UV exposure:
Avoid direct sunlight: Stay indoors during peak sunlight hours (10 AM - 4 PM).
Wear protective clothing: Long sleeves, long pants, wide-brimmed hats, and UV-protective sunglasses.
Use high SPF sunscreen: Apply liberally and frequently, even on cloudy days. Choose a broad-spectrum sunscreen that protects against UVA and UVB rays.
UV-protective film on windows: Apply UV-protective film to car and home windows.
Avoid tanning beds: Tanning beds emit harmful UV radiation and should be strictly avoided.
Regular medical check-ups: Dermatological and neurological evaluations are crucial for early detection and management of complications.
Educate caregivers and family members: Ensure that everyone involved in the care of the individual understands the importance of sun protection.
How long does an outbreak last?
XP-B is not characterized by "outbreaks." It is a chronic condition that manifests with continuous symptoms related to UV sensitivity and DNA repair deficiency. The skin damage and neurological issues are progressive over time. Acute sunburns can occur with even minimal sun exposure and can last days to weeks, but this is an acute effect of the underlying chronic condition.
How is it diagnosed?
Diagnosis of XP-B typically involves:
Clinical evaluation: Assessment of symptoms, including sun sensitivity, skin abnormalities, and neurological problems.
Family history: Gathering information about family history of XP or related conditions.
Skin biopsy: Microscopic examination of skin samples to identify characteristic DNA damage and cellular abnormalities.
Fibroblast studies: Culturing skin cells (fibroblasts) and assessing their ability to repair UV-induced DNA damage.
Genetic testing: DNA sequencing to identify mutations in the ERCC3 gene. This is the most definitive diagnostic test.
Complementation analysis: Historically used, but largely replaced by genetic testing, this method determines the specific XP complementation group.
Timeline of Symptoms
The timeline of symptoms varies but generally follows this pattern:
Infancy/Early Childhood: Extreme sun sensitivity with severe sunburns after minimal exposure. Freckling and pigment changes may appear early.
Childhood/Adolescence: Progressive skin damage, including poikiloderma. Neurological symptoms, such as developmental delays, intellectual disability, or seizures, may become apparent or worsen. Increased risk of skin cancers begins.
Adulthood: Continued skin damage and increased skin cancer risk. Neurological degeneration may progress, leading to worsening of motor skills, cognitive abilities, and other neurological functions. Ocular complications can develop.
Important Considerations
Genetic Counseling: Crucial for families with a history of XP to understand the inheritance pattern and assess the risk of having affected children.
Early Diagnosis and Intervention: Early diagnosis and strict sun protection are essential to minimize skin damage and cancer risk.
Multidisciplinary Care: Management of XP-B requires a team approach involving dermatologists, neurologists, ophthalmologists, geneticists, and other specialists.
Psychosocial Support: The chronic nature of XP-B and its impact on physical appearance and neurological function can lead to emotional and psychological distress. Support groups and counseling can be beneficial.
Research: Ongoing research is focused on developing new treatments for XP, including gene therapy and other innovative approaches.
Avoidance of Carcinogens: Minimize exposure to other environmental carcinogens to reduce the overall burden on DNA repair mechanisms.