Genotype-Phenotype Correlations in Neurofibromatosis and Their Potential Clinical use

Objective:As clinically validated biomarkers for neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2), have not been identified to date, we wanted to determine whether genotype-phenotype correlations are usefull in clinical trials in Neurofibromatosis 1 and 2Methods:The biomarker group first performed a systematic literature search and reviewed existing data on genetic biomarkers in NF1 and NF2 and in in malignant peripheral nerve sheath tumours (MPNST). The group then met during a series of consensus meetings to develop a joint report.Results:We found that In NF2 the genetic severity score is clearly of potential clinical use. In NF1 despite over 3000 constitutional variants having been described in the NF1 gene, only four actionable genotype phenotype correlations currently exist. The diagnosis and treatment decision of these tumours should ideally include histopathology and compilation of some of the genetic markersConclusion:We summarized emerging clinical use of genotype-phenotype correlations in Neurofibromatosis.