The references were obtained between July and October, 2006, by consulting all publications in English and French on PubMed from 1980 to 2006, and the historical literature references were taken from the authors' doctoral thesis. Search terms were “NF1”, “NF2”, “neurofibroma”, “schwannoma”, “gastrointestinal stromal tumour”, “glomus tumour”, “neurofibromin”, and “merlin”.
ReviewNeurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective
Introduction
Previously, neurofibromatosis 1 (NF1) was referred to as von Recklinghausen's disease and neurofibromatosis 2 (NF2) was termed bilateral acoustic or central neurofibromatosis.1, 2 Both disorders were independently documented in the historical literature. Mark Akenside provided a convincing account of NF1 when “in the year of 1761, a man about threescore years of age came to St. Thomas' Hospital…He had been accustomed during the greater part of his life to a constant succession of wens [tumours] that shot out in several places on his head, trunk, arms and legs: which indisposition he inherited from his father.”3 In 1822, NF2 was described in a young baker who presented to the Scottish surgeon James Wishart with progressive deafness affecting both ears. He succumbed to septicaemia after surgery for a cranial tumour. Post-mortem identified multiple tumours of the dura mater and brain in addition to bilateral tumours of the eighth nerve.4
Despite these early descriptions, NF1 and NF2 were not demarcated or defined as separate diseases until the end of the twentieth century.5 Recent progress in molecular biology, advances in neuroimaging, and the development of mouse models have provided an insight into the pathogenesis of these complex disorders and the prospect of drug treatment. In this Review, I discuss the current diagnostic and clinical features of NF1 and NF2 and the management of its complications. This Review will highlight the molecular advances that have permitted a biological approach to targeted therapies for tumours and the development of clinical trials.
Section snippets
Epidemiology and differential diagnosis
NF1 has a birth incidence of one in 2500 to one in 3000 and a minimum prevalence of one in 4–5000.6 The National Institute of Health (NIH) Consensus Development Conference formulated the current diagnostic criteria and proposed the name neurofibromatosis 1 (NF1; panel 1).5 Macrocephaly and stature at 10th–25th percentile are not diagnostic of the disorder, but are common minor disease characteristics.7
The conspicuous loophole in the NIH diagnostic stipulations is that café au lait patches may
Epidemiology and differential diagnosis
NF2 has a birth incidence of about one in 25 000 and an annual incidence of one in 2 355 000.86 The discrepancy between birth incidence and incidence of newly diagnosed symptomatic patients arises because many individuals do not develop clinical problems until adulthood and others die. The diagnostic prevalence of NF2 was reported in 1992 as one in 210 000, but is likely to be higher because patients' survival has increased and modern neuroimaging and genetic testing allows early diagnosis of
Conclusions
NF1 and NF2 are tumour predisposition syndromes, but undoubtedly they are distinct clinical and genetic disorders. The time is ripe to rename NF2, to indicate that the hallmark tumours are schwannomas and meningiomas. Progress in molecular biology and the burgeoning of mouse models offer the hope of understanding the pathogenesis of neurofibromas, schwannomas, and optic pathway gliomas, while enhancing our understanding of sporadic tumour formation. The task of twenty first century clinicians
Search strategy and selection criteria
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