Karyomegalic Interstitial Nephritis: Cancer Risk Following Transplantation.

A brother and sister presented individually in their forties with progressive renal failure, bronchiectasis and mild derangements of their liver function tests. Both developed end-stage renal disease before the age of 50. Both siblings were found to carry a pathogenic, recessive, compound heterozygote mutation in the gene FAN1, which causes karyomegalic interstitial nephritis. Both siblings underwent renal transplantation. The sister developed small cell carcinoma of the lung 18 months after transplantation. Despite intensive chemotherapy she died 6 months later. Six years after transplant, the brother has developed prostate cancer and over 30 individual skin cancers. To our knowledge, only 6 other patients with FAN1 mutations have undergone solid organ transplantation. Outcomes have been poor, with only 3 patients surviving beyond 1 year. While cancer is a significant risk for all patients in the post-transplant period, only 0.01% of patients develop >10 skin cancers. Transplantation may be an unrecognised risk in patients with FAN1 mutations.