Background: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by a decreased ability to repair DNA damaged by UV radiation and the early development of cutaneous and ocular malignant neoplasms. Approximately 20% of patients with XP also develop progressive neurologic degeneration.
Observations: We describe a boy who was found to have XP after a severe burn following minimal sun exposure. His maternal uncle, now age 20 years, had been diagnosed with XP after a similar sunburn in infancy. The uncle has the typical skin pigmentary findings of XP along with severe progressive neurologic involvement. Although the infant's parents were not known to be blood relatives, the infant and his affected uncle proved to be compound heterozygotes for the same 2 frameshift mutations in the XPA DNA repair gene (c.288delT and c.349_353del). After the diagnosis of XP in the infant, genealogic investigation identified a common Dutch ancestor for both of his grandfathers 5 generations back.
Conclusions: Counseling families at risk for a rare inherited disease is not always straightforward. The sociocultural and demographic backgrounds of the families must be considered for evaluation of risk assessment.