Neurofibromatosis type 1

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Abstract

Neurofibromatosis type 1 is a complex autosomal dominant disorder caused by germline mutations in the NF1 tumour suppressor gene. Nearly all individuals with neurofibromatosis type 1 develop pigmentary lesions (café-au-lait macules, skinfold freckling and Lisch nodules) and dermal neurofibromas. Some individuals develop skeletal abnormalities (scoliosis, tibial pseudarthrosis and orbital dysplasia), brain tumours (optic pathway gliomas and glioblastoma), peripheral nerve tumours (spinal neurofibromas, plexiform neurofibromas and malignant peripheral nerve sheath tumours), learning disabilities, attention deficits, and social and behavioural problems, which can negatively affect quality of life. With the identification of NF1 and the generation of accurate preclinical mouse strains that model some of these clinical features, therapies that target the underlying molecular and cellular pathophysiology for neurofibromatosis type 1 are becoming available. Although no single treatment exists, current clinical management strategies include early detection of disease phenotypes (risk assessment) and biologically targeted therapies. Similarly, new medical and behavioural interventions are emerging to improve the quality of life of patients. Although considerable progress has been made in understanding this condition, numerous challenges remain; a collaborative and interdisciplinary approach is required to manage individuals with neurofibromatosis type1 and to develop effective treatments.

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Figure 1: Benign peripheral nerve sheath tumours.
Figure 2: Development of clinical features of neurofibromatosis type 1.
Figure 3: Neurofibromin signalling pathway.
Figure 4: Pigmentary features of neurofibromatosis type 1.
Figure 5: Pathogenesis of plexiform neurofibromas.
Figure 6: Pathogenesis of optic pathway gliomas.
Figure 7: Skeletal defects in neurofibromatosis type 1.
Figure 8: Central nervous system abnormalities.
Figure 9: Biopsychosocial factors affecting quality of life in neurofibromatosis type 1.

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Acknowledgements

This work was partially funded by a grant from the US Department of Defense (W81XWH-12-1-0155 to B.R.K.).

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Introduction (B.R.K.); Epidemiology (K.J.J.); Mechanisms/pathophysiology (D.H.G.); Diagnosis, screening and prevention (R.E.F.); Management (R.H.L. and R.E.F.); Quality of life (P.L.W.); Outlook (B.R.K.); Overview of Primer (D.H.G.).

Correspondence to David H. Gutmann.

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