[PS10-2B-2] Neurofibromatosis 1
Neurofibromatosis 1 (NF1) is an autosomal dominant disorder that affects approximately 1 in 3500 persons worldwide. NF1 is caused by mutation of NF1, encoding for the tumour suppressor protein, neurofibromin. Neurofibromin is a negative regulator of Ras proto-oncogene, an important signalling molecule in the control of cell growth. It is the most frequent inherited genetic syndrome resulting in peripheral nerve sheath tumours and neoplasia is the most frequent cause of morbidity. Individuals with NF1 have multi-organ manifestations involving the skin, eye, bone, cardiovascular system, central and peripheral nervous system. Diagnosis of NF1 is clinical, with well established diagnostic criteria. However, due to the clinical heterogeneity in presentation, the diagnosis may be missed or delayed.
With detailed understanding of neurofibromin-controlled signalling pathways and development of mouse models of NF1-associated tumours, rational targeted treatment is now a possibility. Clinical trials with drugs targeting to reduce hyperactivity of the RAS and mTOR pathways have become available, although none have demonstrated significant benefit. Currently there is no effective drug treatment for NF1, thus early detection of manageable complications and genetic counselling remains the best approach.
With detailed understanding of neurofibromin-controlled signalling pathways and development of mouse models of NF1-associated tumours, rational targeted treatment is now a possibility. Clinical trials with drugs targeting to reduce hyperactivity of the RAS and mTOR pathways have become available, although none have demonstrated significant benefit. Currently there is no effective drug treatment for NF1, thus early detection of manageable complications and genetic counselling remains the best approach.