Neurofibromatosis 2 and Related disorders

The neurofibromatoses consist of at least three autosomal dominantly inherited disorders, neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis. For over 80 years these conditions were inextricably tied together under generalised neurofibromatosis. In 1987 the localisation of NF1 to chromosome 17q and NF2 (bilateral vestibular schwannoma) to 22q led to a consensus conference at Bethesda. The two main neurofibromatoses NF1 and NF2 were formally separated. More recently the SMARCB1 and LZTR1 genes on 22q have been confirmed as causing a subset of schwannomatosis. The last 26 years has seen a great improvement in understanding of the clinical and molecular features of these conditions as well as insights into management. Childhood presentation of NF2 (often with meningioma) in particular predicts a severe multi-tumor disease course. Malignancy is rare in NF2 particularly in childhood, however, there are substantial risks from benign and low-grade CNS tumors necessitating MRI surveillance to optimize management. At least annual brain MRI, including high resolution images through the auditory meatus, and a clinical examination and auditory assessment are required from diagnosis or from around 10-12 years of age if asymptomatic. Spinal imaging at baseline and every 2-3 years is advised with more frequent imaging if warranted based on sites of tumor involvement. The malignancy risk in schwannomatosis is not well defined but may include an increased risk of malignant peripheral nerve sheath tumor in SMARCB1. Imaging protocols are also proposed for SMARCB1 and LZTR1 schwannomatosis and SMARCE1 related meningioma predisposition.