[Neurofibromatosis: the most frequent hereditary tumor predisposition syndrome].
With an incidence of one in 3000 to 4000 individuals, neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant genetic diseases and very likely the most frequent disorder with increased cancer risk. Approximately fifty percent of all patients are familial cases and the remaining half consists of sporadic cases with no affected parent. The hallmark clinical features present in over 90% of all patients are café-au-lait spots and neurofibromas. However, the disorder should not be underestimated as a "mere cosmetic problem", since NF1 patients are at increased risk to also develop malignant tumours, such as malignant peripheral nerve sheath tumours (MPNST), juvenile myelomonocytic leukaemia (JMML), optic glioma and pheochomocytoma. Renovascular disease represents an additional risk factor for NF1 patients. The NF1 gene is a classic example for a tumour suppressor gene. It functions as a negative regulator of the protooncogene Ras. This function explains well its involvement in tumour formation. During the last 15 years, since the cloning of the gene, enormous progress has been made towards a better understanding of the natural history of the disorder. However, it cannot be said if and when a cure of the disorder will be possible. Great advantages have been achieved in the monitoring and management of several NF1 complications, for instance in the treatment of tibia pseudarthrosis and optic gliomas. Owing to the technical improvements of the approaches applied to identify NF1-mutations molecular-genetic testing with high mutation detection rates may help nowadays in patients in which the clinical diagnosis may not readily be established, such as in young children or atypical cases. A greater awareness of the complications and the different expression forms of NF1 and NF2 on the part of all types of physicians will further help to offer all patients adequate and timely counselling and treatment. The establishment of multi-disciplinary counselling and treatment centres for neurofibromatosis could be an important step towards a better management of NF1 and NF2 patients.
Wimmer
Katharina
K
Abteilung für Humangenetik, Klinisches Institut für Medizinische und Chemische Labordiagnostik, Medizinische Universität Wien, Wien, Osterreich. katharina.wimmer@meduniwien.ac.at
D000293:Adolescent; D000328:Adult; D002648:Child; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D004198:Disease Susceptibility; D005799:Genes, Dominant / Q000235:genetics*; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D009386:Neoplastic Syndromes, Hereditary / Q000175:diagnosis / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000175:diagnosis / Q000235:genetics*; D025542:Neurofibromin 1 / Q000235:genetics; D025581:Neurofibromin 2 / Q000235:genetics; D010641:Phenotype; D012306:Risk
D025542:Neurofibromin 1; D025581:Neurofibromin 2