Neurofibromatosis Type 1 (NF1) and Tibial Dysplasia

Multicenter Study of Tibial Dysplasia in Neurofibromatosis Type I (NF1) Patients

The study is a multicenter four-year outcome study of the natural history of tibial dysplasia in patients with NF1 and selected patients without NF1. We will obtain information on the natural history, burden, functional and health status, health-related quality of life, and surgical interventions/outcomes of tibial dysplasia. The project will also establish a Core Facility (NOCF) for tissue samples for future studies.

The three specific aims of this study are:

• Specific Aim 1 - To assess health status and health - related quality of life (HRQL) in 50 children and adolescents with NF1 and tibial dysplasia and in NF1 controls. We hypothesize that children and adolescents with NF1 and tibial dysplasia will experience an additional burden of morbidity due to tibial dysplasia and a downward trajectory of health status and HRQL over time.
• Specific Aim 2 - To assess the long term outcome of current treatment in 100 adult patients diagnosed with NF1 and tibial dysplasia in childhood. We hypothesize that better quality of life and function, in adults with NF1 and tibial dysplasia, are associated with amputation in childhood compared to multiple surgical procedures, the lack of fibular involvement, and fracture later in childhood. We also hypothesize that individuals with NF1 and tibial dysplasia have a higher risk of other bony dysplasias but are at no higher risk of fracture in other bones.
• Specific Aim 3 - To assess the natural history and short-term response to therapy in a cohort of at least 60 children with NF1 and tibial dysplasia and at least 60 children with tibial dysplasia presumably without NF1 prospectively diagnosed during the course of the four-year study period. We hypothesize that NF1 patients with earlier presentation, Crawford Class II A-C, male gender, and the lack of bracing prior to age two are more likely to fracture. We also postulate that individuals with and without NF1 have a similar outcome and response to treatment.

The results of this project will provide a rational basis for future clinical and therapeutic trials.

Inclusion Criteria:

• Aim 1:

  • Group 1, NF1 with Tibial Dysplasia, Ages: 3-18
  • Group 2 (control), NF1 without Tibial Dysplasia, Ages 3-18

• Aim 2: NF1 with Tibial Dysplasia, 19+

• Aim 3: Tibial Dysplasia with or without NF1, Ages: birth to 18

• Tissue procurement, any participant undergoing surgery at the tibial site for routine standard of care

Exclusion Criteria:

• Patients without a diagnosis of NF1 or Tibial Dysplasia