Neurofibromatosis type 1– unpredictable disease?
Keywords:
Neurofibromatosis type 1, von Recklinghausen’s disease, NF1, neurofibromas, neurofibrosarcomas, café-au-lait spots, neurofibrominAbstract
Neurofibromatosis type 1 (NF1), also known as Von
Recklinghausen’s disease, was first described in 1882, and it is
the most frequent of the neurocutaneous syndromes.
It is one of the most common genetic disorders, which responsible gene is located in the long arm of chromosome 17, with a
1/2500 incidence rate, with dominant autosomal transmission,
being half of the cases familial and the other half sporadic.
The diagnosis is based on the presence of at least 2 of 7
criteria established on the National Institute of Health Consensus
Conference of Bethesda in 1987.
Although in adults the diagnosis is rather easy, when it comes
to children the café-au-lait spots may be, for a long period of time
the only sign, keeping the disease undiagnosed.
Besides the typical café-au-lait and neurofibromas there is
an aggravated risk of developing malignant neoplasms, namely
malignant peripheral nerve sheaths tumors also referred to as
schwannomas or neurofibrosarcomas.
These neurofibrosarcomas have a smaller response to the
conventional cancer treatment, and it is believed that many genetic
factors are responsible for their higher aggressiveness.
Malignant tumors are the main cause of death by NF1, being
associated to mortality at tender age. The case we describe is
such an example.
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References
Huson SM, Hughes RAC. The Neurofibromatosis: A Pathogenic and Clinical Overview. London: Chapman and Hall 1994.
Riccardi VM. Neurofibromatosis: Phenotype, Natural History, and Pathogenesis. Johns Hopkins University Press, Baltimore 1992.
Stephens K, Kayes L, Riccardi VM et al. Preferential mutation of the neurofibromatosis type 1 gene in paternally derived chromosomes. Hum Genet 1992; 88:279.
Friedmnan JM, Birch PH. Type 1 neurofibromatosis- a descriptive analysis of the disorder in 1,728 patients. Am J Med Genet 1997; 70:138-143.
Shen MH, Harper PS, Upadhyaya M. Molecular genetics of neurofibromatosis type 1 (NF1). J Med genet 1996; 33:2-17.
Upadhyaya M, Cooper DN. The mutational spectrum in neurofibromatosis type 1 and its underlying mechanisms. In M Upadhyaya & DN Cooper (Eds.), Neurofibromatosis type 1: From genotype to phenotype. Oxford: BIOS Scientific1998;65-82.
Martin GA, Viskochil D, Bollag G et al. The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21. Cell 1990; 63:843.
Arun D, Gutmann DH. Recent Advances in Neurofibromatosis Type 1; Current Opinion in Neurology 2004; 17:101-105.
Tong J, Hanna F, Zhu Y et al. Neurofibromin regulates G-protein –stimulated adenylyl cyclase activity. Nat Neurosci 2002; 5:95-96.
Szudeck et al. Analysis of intrafamilial phenotypic variation in neurofibromatosis 1(NF1). Genetic Epidemiology 2002; 23:150-164.
Kluwe L, Friedrich RE, Peiper M et al. Constitutional NF1 mutations in neurofibromatosis 1 patients with malignant peripheral nerve sheath tumors. Hum Mutat 2003; 22:420.
De Bella et al. Use of the NIH criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics 2000; 105:608-614.
Gutmann DH, Collins FS. Neurofibromatosis 1. In: The Metabolic and Molecular Bases of Inherited Disease, Scriver, CR, Beaudet, AL, Sly, WS, Valle, D (Eds), McGraw-Hill, New York 2001;877.
Friedman, JM, Riccardi, VM. Clinical and epidemiologic features. In J.M. Friedman, D.H. Gutmann, M. MacCollin, & V.M. Riccardi (Eds.), Neurofibromatosis: Phenotype, natural history, and pathogenesis (3rd ed.). The Johns Hopkins University Press, Baltimore 1999;29-86.
Gutmann DH, Rasmussen SA, Wolkenstein P et al. Gliomas presenting after age 10 in individuals with neurofibromatosis type 1 (NF 1). Neurology 2002; 59:759.
Guillamo JS, Creange A, Kalifa C et al. Prognostic factors of CNS tumors in Neurofibromatosis 1 (NF1): a retrospective study of 104 patients. Brain 2003; 126:152.
Korf BR. Malignancy in neurofibromatosis type 1. Oncologist 2000; 5: 477-485.
Listernick R, Charrow J, Gutmann DH. Intracranial gliomas in neurofibromatosis type 1. American journal of Genetics 1999; 89: 38-44.
Czyzyk E, Jozwaik S, Roszkowski M et al. Optic pathway gliomas in children with and without neurofibromatosis 1. J Child Neurol 2003; 18:471-478.
Riccardi VM. Skeletal system. In JM, Friedman, DH, Gutmann, M, MacCollin, VM, Riccardi (Eds.), Neurofibromatosis: Phenotype, natural history, and pathogenesis (3rd ed.), The Johns Hopkins University Press. Baltimore 999;250-273.
Kuorilehto T et al. Decreased bone mineral density and content in neurofibromatosis type 1: local lowest values are located in the load-carrying parts of the body. Osteoporosis International 2005; 16: 928-936.
Peltonen J et al. Cellular differentiation and expression of matrix genes in the type 1 neurofibromatosis. Laboratory Investigation 1988; 59: 760-771.
Dugoff L, Sujansky E. Neurofibromatosis type 1 and pregnancy. Am J Med Genet 1996; 66:7-10.
Evans DG, Baser ME, McGaughran J et al. Malignant peripheral nerve sheath tumors in neurofibromatosis type 1. J Med Genet 2002; 39:311-314.
Levy A, et al. From the archives of the AFIP: Abdominal neoplasms in patients with neurofibromatosis type 1: Radiologic-pathologic correlation. Radiographics 2005; 25:455-480.
Li H, Velasco-Migual S, Vass WC et al. Epidermal growth factor receptor signaling pathways are associated with tumorigenesis in the Nf1: p53 mouse tumor model. Cancer Res 2002; 62:4507-4513.
Su W, Sin M, Darrow A et al. Malignant peripheral nerve sheath tumor cell invasion is facilitated by Src and aberrant CD44 expression. Glia 2003; 42:350-358.
Miller SJ, Li H, Rizvi TA et al. Brain lipid bindig protein in axon-Schwann cell interactions and peripheral nerve tumorigenisis. Mol Cell Biol 2003; 23:2213-2224.
Perry A, Kunz F, Fuller CE et al. Differential NF1, p16, and EGFR patterns by interphase cytogenetics (FISH) in malignant peripheral nerve sheath tumor (MPST) and morphologically similar spindle cell neoplasms. J Neuropathol Exp Neurol 2002; 61:702-709.
Pinson S, Wolkenstein P. La neurofibromatose 1 (NF1) ou maladie de Von Recklinghausen; La revue de medicine interne 26 2005;196-215.
Rasmussen SA, Yang Q, Friedman JM. Mortality in neurofibromatosis 1: an analysis using U.S. death certificates. Am J Hum Genet 2001; 68:1110-1118.
Khosrotehrani K et al. Factors associated with mortality in neurofibromatosis type 1. American Journal of Medical Genetics 2005; 132:49-53.
Hyman SL, Shores A, North KN. The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology 2005; 65:1037-1044.
Carmi D, Shohat M, Metzker A, Dickerman Z. Growth, puberty, and endocrine functions in patients with sporadic or familial neurofibromatosis type 1: A longitudinal study. Pediatrics 1999; 103:1257-1262.
Friedman JM et al. Cardiovascular disease in neurofibromatosis 1: Report of the NF1 cardiovascular task. Genetics in Medicine 2002; 4:105-111.
Denckla MD et al. Relationship between T2 weighted Hyperintensities (unidentified bright objects) and lower IQs in children with neurofibromatosis-1. American Journal of Medical Genetics 1996; 67:98-102.
Hyman SL et al. Natural history of cognitive deficits and their relationship to MRI T2-hyperintensities in NF1. Neurology 2003; 60: 1139-1145.
Rosenbaum T, Engelbrecht V, Krolls W et al. MRI abnormalities in neurofibromatosis type 1 (NF1): a study of men and mice. Brain Dev 1999; 21:268.
Aoki S et al. Neurofibromatosis type 1 & 2: Cranial MR findings. Radiology 1989; 172:527-534.
Ruggieri M, Huson SM. The clinical and diagnostic implications of mosaicism in the neurofibromatosis. Neurology 2001; 56:1433.
Rouleau GA et al. Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. Nature 1987; 329:246-248.
Sorensen SA, Mulvihill JJ, Nielsen A. Long-term follow-up of von Recklinghausen neurofibromatosis. Survival and malignant neoplasms. N Engl J Med 1986; 314:1010.
Messiaen LM et al. Exhaustive mutation analysis of the NF1 gene allows identification of 95 % of mutations and reveals a high frequency of unusual splicing defects. Human mutation 2000; 15:541-555
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