Neurofibromatosis 1 (NF1) is a common autosomal dominant disease with an estimated birth incidence of 1 in 2500 and a prevalence of 1 in 4000 (Huson et al., 1991). The principal and defining clinical features are café au lait patches, skinfold freckling, cutaneous neurofibromas (benign peripheral nerve sheath tumours), iris Lisch nodules (hamartomas) and characteristic bony dysplasia (Huson et al., 1988; National Institutes of Health Consensus Development Conference, 1988) (Table 1). The majority of patients are diagnosed by the age of three years. NF1 arises as a spontaneous mutation in 50% of individuals and there is a wide variety of disease expression in patients with NF1, even within families. Neurofibromatosis 1 is clinically and genetically distinct from the rare condition neurofibromatosis 2, which is characterized by bilateral vestibular schwannomas (benign tumours of the eighth cranial nerve), schwannomas involving other cranial nerves, spinal nerve roots and peripheral nerves and by central nervous system meningiomas and gliomas (Evans et al., 1992).
The gene for NF1 has been identified on chromosome 17q11.2 by positional cloning (Viskochil et al., 1990; Wallace et al., 1990) and the protein product is neurofibromin, which has high levels of expression in the brain and acts as a tumour suppressor (Gutmann et al., 1991). Neurofibromin reduces cell proliferation by promoting the inactivation of the protooncogene p21RAS, which has a major role in mitogenic intracellular signalling pathways.