Familial Lipomas Without Classic Neurofibromatosis-1 Caused by a Missense Germline NF1 Mutation

Neurofibromatosis type 1 (NF1; OMIM 162200) is an autosomal dominant disorder caused by a wide variety of germline mutations in the NF1 gene. Nearly all individuals with NF1 exhibit cafe-au-lait macules before the age of 2,1 but can also develop numerous other medical problems, including autism, cognitive deficits, tumors, and congenital heart defects. Although the clinical variability inherent in NF1 has been attributed to stochastic events, it is possible that the specific germline NF1 mutation might be one factor underlying this heterogeneity. To illustrate this point, we report a family with 2 affected members harboring a missense mutation in the NF1 gene who lack the classic features of NF1.