Epidemiology
Etiology
- Autosomal recessive (AR) disorder.
- Defect in nucleotide excision repair (NER), which is responsible for removing bulky helix-distorting DNA lesions.
- Specifically, NER is unable to repair pyrimidine dimers (e.g., thymine dimers) that form in DNA as a result of UV light exposure.
Pathophysiology
Clinical features
-
Presents in early childhood (<2 years old).
- Extreme photosensitivity: Severe sunburn, blistering, and persistent erythema after minimal sun exposure.
- Cutaneous findings:
- Dry, scaly skin (xeroderma).
- Freckle-like hyperpigmented macules (pigmentosum) in sun-exposed areas.
- Poikiloderma (atrophy, telangiectasias, hyper/hypopigmentation).
- Ocular findings:
- Photophobia, conjunctivitis, keratitis.
- Increased risk of ocular neoplasms (e.g., squamous cell carcinoma, melanoma).
- Neurologic findings (in ~20-30% of patients):
- Progressive neurodegeneration.
- Sensorineural hearing loss, cognitive impairment, ataxia, areflexia.
-
Complications/Prognosis
-
1000-fold ↑ risk of skin cancer, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.
-
Cancers develop at a very young age (median age ~10 years).
-
Significantly reduced life expectancy, primarily due to metastatic skin cancer or neurodegeneration.
-