Xeroderma pigmentosum (XP) is a rare genetic disorder characterized by extreme sensitivity to ultraviolet (UV) light from sunlight and artificial sources such as fluorescent lights. It is primarily a dermatological condition but can also involve neurological and ophthalmological manifestations. XP is caused by mutations in genes involved in DNA repair, leading to the inability of cells to repair damage caused by UV radiation effectively.

Symptoms:

1. Skin Changes:
   • Severe sunburn and blistering after minimal sun exposure.
   • Freckle-like pigmentation, especially in sun-exposed areas.
   • Development of numerous skin lesions, including actinic keratoses, basal cell carcinoma, squamous cell carcinoma, and melanoma at a young age.
2. Eye Abnormalities:
   • Photophobia (sensitivity to light).
   • Eye irritation and inflammation.
   • Development of ocular surface neoplasms (tumors) such as squamous cell carcinoma on the conjunctiva.
3. Neurological Symptoms:
   • Intellectual disability or developmental delay in some cases.
   • Progressive neurological degeneration, leading to hearing loss, difficulty with coordination and balance, and cognitive impairment.

Causes:

• Xeroderma pigmentosum is caused by mutations in genes involved in nucleotide excision repair (NER), a process essential for repairing damage to DNA caused by UV radiation.
• Mutations in any of the XP genes (XP-A to XP-G) or the XP variant gene (XP-V) can lead to the development of XP.

Diagnosis:

• Clinical Evaluation: Based on symptoms such as extreme sun sensitivity, skin changes, and a history of skin cancers.
• DNA Repair Assays: Laboratory tests to assess the DNA repair capacity of skin cells in response to UV radiation exposure.
• Genetic Testing: Molecular genetic testing can identify mutations in genes associated with XP.

Treatment:

• Sun Protection: Strict sun protection measures are essential, including wearing protective clothing, hats, and sunglasses, and avoiding sun exposure during peak hours (10 am to 4 pm).
• Topical Treatments: Regular application of broad-spectrum sunscreen with a high SPF to protect the skin from UV radiation.
• Regular Skin Checks: Routine skin examinations by a dermatologist to monitor for signs of skin cancer and other sun-related complications.
• Surgical Intervention: Surgical removal of skin cancers as necessary, often requiring close collaboration between dermatologists, surgeons, and oncologists.
• Symptomatic Management: Treatment of symptoms such as photophobia and eye problems with supportive measures and medications as needed.

Prognosis:

• The prognosis for individuals with XP varies depending on the severity of their condition and the extent of sun exposure.
• With strict sun protection measures and regular monitoring, individuals with XP can lead relatively normal lives, although they remain at high risk for skin cancer and other complications.

Genetic Counseling:

• Genetic counseling is essential for individuals with XP and their families to understand the inheritance pattern of the disorder and the risk of passing on the mutated gene to future generations.
• Prenatal testing may be offered to families with a history of XP to determine the risk of having affected offspring.

Research and Support:

• Ongoing research is focused on developing novel therapies and improving understanding of XP pathophysiology.
• Support groups and patient advocacy organizations provide valuable resources and support for individuals and families affected by XP.