Tibial Bowing and Pseudarthrosis in Neurofibromatosis Type 1

Anterolateral tibial bowing is a morbid skeletal manifestation observed in 5 of children with neurofibromatosis type 1 NF1, typically identified in infancy. The majority of NF1 individuals with tibial bowing will sustain a fracture that will not heal i.e. pseudarthrosis resulting in multiple surgeries, poor limb function, and amputation. Some NF1 individuals with tibial bowing, however, do not fracture and the bowing improves over time. Clinical predictors to help drive management are lacking, and the pathophysiology of tibial bowing and pseudarthrosis is not well understood. Our objective was to identify clinical predictors of tibial pseudarthrosis and better understand its pathophysiology. The data showed that quantitative bone ultrasound was able to distinguish an affected leg in individuals with neurofibromatosis type 1 NF1. This further confirms a decrease of bone mineralization of the bowed tibia. The importance of this finding is that this can now be used as an outcome measure for clinical trials.. We also confirmed the molecular etiology of tibial dysplasia as double inactivation of the NF1 gene. In addition, we provide evidence that the periosteum likely harbors the somatic mutation.