Non-neoplastic causes of death in neurofibromatosis 1: A cohort study with long-term follow-up.

Neurofibromatosis 1 (NF1) is associated with reduced life expectancy due to malignancies; however, the risk of non-neoplastic causes of death is less well characterised. A total of 1622 persons with NF1, identified through either the Danish National Patient Registry or a clinical database, and 15856 matched comparators born 1951-2002 were followed from either age 20 or NF1 diagnosis. Death causes were from the Danish Cause of Death Register. Cumulative risks of different causes of death were compared between persons with and without NF1, and years of life lost (YLL) were calculated. Overall, 259 persons with NF1 (16.0%) and 578 comparators (3.6%) died during follow-up. The most frequent non-neoplastic causes of death in NF1 were diseases in the circulatory and nervous systems, with the latter showing a statistically significant higher 70-year cumulative risk in NF1. An excess of 6.1 (4.7-7.5) YLL within age 20-60 was seen in NF1 including 2.5 (1.5-3.5) years from non-neoplastic causes, and 3.6 (2.5-4.7) years from neoplasms. Persons with NF1 showed an increased risk of death from nervous system diseases and neoplasms and a reduced life expectancy, with non-neoplastic causes accounting for almost half of the YLL.