Summary about Disease
Xeroderma pigmentosum complementation group B (XP-B) is a rare, inherited genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation from sunlight. This sensitivity leads to a high risk of developing skin cancers, neurological problems, and other complications. XP-B is one of several subtypes of Xeroderma pigmentosum, each resulting from a mutation in a different gene involved in DNA repair. XP-B is particularly severe because the ERCC3 gene, which is affected, plays a crucial role in nucleotide excision repair and also in transcription.
Symptoms
Extreme sun sensitivity (sunburns easily, even with minimal sun exposure)
Severe blistering after sun exposure
Freckling in sun-exposed areas at a young age
Dry, scaly skin (xeroderma)
Changes in skin pigmentation (uneven coloring)
Increased risk of skin cancers (basal cell carcinoma, squamous cell carcinoma, melanoma) at a young age
Eye problems (sensitivity to light, conjunctivitis, corneal damage)
Neurological abnormalities (developmental delay, intellectual disability, seizures, hearing loss, ataxia)
Progressive neurological degeneration
Premature aging of the skin
Causes
XP-B is caused by mutations in the ERCC3 gene. This gene provides instructions for making a protein that is part of the TFIIH complex. The TFIIH complex is involved in two important processes:
Nucleotide Excision Repair (NER): NER is a DNA repair mechanism that removes UV-induced DNA damage (e.g., thymine dimers).
Transcription: TFIIH is involved in the initiation of transcription, the process by which DNA is copied into RNA. Mutations in ERCC3 impair both NER and transcription, leading to the characteristic features of XP-B. It is inherited in an autosomal recessive pattern, meaning an affected individual must inherit two copies of the mutated gene (one from each parent).
Medicine Used
There is no cure for XP-B. Treatment focuses on managing symptoms and preventing complications. Common approaches include:
Strict Sun Protection:
High SPF sunscreens (broad-spectrum, SPF 30 or higher)
Protective clothing (long sleeves, hats, sunglasses)
Avoiding sun exposure, especially during peak hours
Regular Skin Examinations: Frequent skin exams by a dermatologist to detect and treat skin cancers early.
Surgical Removal of Skin Cancers: Skin cancers are typically removed surgically.
Topical Medications: Creams or ointments to treat precancerous skin lesions.
Treatment for Eye Problems: Artificial tears, ointments, or surgery to manage eye dryness and damage.
Supportive Care: Management of neurological symptoms and developmental delays may involve physical therapy, occupational therapy, speech therapy, and other supportive measures.
Vitamin D supplementation: important, as sun avoidance can cause vitamin D deficiency.
Experimental Therapies: Research is ongoing to develop new therapies for XP, including gene therapy and other approaches.
Is Communicable
No, XP-B is not communicable. It is a genetic disorder caused by inherited gene mutations and cannot be spread from person to person.
Precautions
Strict and lifelong sun protection: This is the most critical precaution.
Regular medical follow-up: Frequent visits to a dermatologist, ophthalmologist, and neurologist are essential.
Genetic counseling: If you have a family history of XP, genetic counseling can help determine your risk of carrying the mutated gene.
Educating caregivers and family members: It is important to educate those around the affected individual about the importance of sun protection and other precautions.
Indoor environment: Ensure adequate lighting indoors to reduce reliance on sunlight.
UV-protective window film: Application to car and home windows can reduce UV exposure.
How long does an outbreak last?
XP-B is not characterized by "outbreaks." It is a chronic condition. However, acute sunburn reactions can occur with even minimal sun exposure and may last for days or weeks depending on the severity. The symptoms of the disease are ongoing throughout the individual's life.
How is it diagnosed?
Diagnosis of XP-B typically involves:
Clinical Evaluation: Assessment of symptoms, including extreme sun sensitivity, skin changes, and neurological problems.
Skin Biopsy: A skin sample is examined under a microscope to look for characteristic changes associated with XP.
DNA Repair Assays: Tests to measure the ability of cells to repair UV-induced DNA damage.
Genetic Testing: Analysis of the ERCC3 gene to identify mutations.
Neurological Evaluation: Assessments to evaluate neurological function and developmental milestones.
Timeline of Symptoms
Infancy/Early Childhood: Extreme sun sensitivity, blistering after minimal sun exposure, excessive freckling.
Childhood/Adolescence: Development of dry skin, changes in skin pigmentation, increased risk of skin cancers. Neurological symptoms may begin to appear.
Adulthood: Continued risk of skin cancers, progressive neurological degeneration, premature aging of the skin. The severity and progression of neurological symptoms can vary.
Important Considerations
Early diagnosis is crucial: Early diagnosis and strict sun protection can significantly improve the prognosis and reduce the risk of skin cancers.
Multidisciplinary care is essential: Management of XP-B requires a team of specialists, including dermatologists, ophthalmologists, neurologists, geneticists, and other healthcare professionals.
Psychological support: Living with XP-B can be challenging, and psychological support may be helpful for affected individuals and their families.
Research: Ongoing research is focused on developing new therapies for XP and improving the quality of life for those affected.
Family Support: XP-B affects the entire family. Support groups and resources can provide valuable assistance.
Avoiding artificial UV radiation: Tanning beds and other sources of artificial UV radiation should be strictly avoided.