NF1 is caused by mutations in the gene that controls production of a protein called neurofibromin (neurofibromin 1). This gene is believed to function as a tumor suppressor. In about 50 percent of people with NF1, the disorder results from gene mutations that occur for unknown reasons ("spontaneous mutation"). In others with the disorder, NF1 is inherited "autosomal dominant inheritance pattern,".

NF2 results from mutations in a different tumor-suppressing gene (neurofibromin 2, merlin). Some people with NF2 experience a gene mutation that occurs for unknown reasons ("spontaneous mutation"), while others inherit it from their parent(s) ("autosomal dominant inheritance pattern,".

While schwannomatosis is not well-understood, it is estimated that 85 percent of cases have no known cause ("spontaneous") and 15 percent are inherited.