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Etiology

NF1 is caused by a germline mutation in the NF1 gene; however, only 50% of all individuals with NF1 have an affected parent.[11] These individuals without a family history of NF1 represent new mutations, which presumably arise from a mutation in the NF1 during spermatogenesis in the male.[12] Since NF1 is an autosomal-dominant disorder with complete penetrance, the risk of transmitting NF1 is 50% with each pregnancy. Children who inherit a mutated (nonfunctional) copy of the NF1 gene have NF1, yet the clinical manifestations may be variable. In this regard, a child with NF1 with the identical NF1 gene mutation as a parent or sibling can be more severely or more mildly affected. Moreover, there are no obvious genotype–phenotype correlations that predict disease severity, with the exception of children with large chromosomal deletions surrounding the NF1 gene. These children frequently have mental retardation and distinctive facial features, and may be at risk for the development of malignancy.[…]