Abstract
Introduction
Neurofibromatosis type I (NF1) is one of the most prevalent genetic diseases of the nervous system. Although the majority of NF1 patients are only mildly affected, the risk of develo** malignancies is significantly increased in this population.
Case report
Here, we present a 9-year-old girl with clinical stigmata of NF1 and a rapidly evolving glioblastoma multiforme. Molecular genetic analysis uncovered a novel missense mutation in Exon 32 of the NF1 gene [c.6032C>A(p.Ala2011Glu)].
Discussion
The girl’s death 3 days after diagnosis of the brain tumor exemplifies that NF1 still is a life-threatening disease despite its generally benign course in most patients. However, it remains questionable if a fatal course as reported here can be prevented by routine MRI screening.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bajenaru ML, Zhu Y, Hedrick NM, Donahoe J, Parada LF, Gutmann DH (2002) Astrocyte-specific inactivation of the neurofibromatosis 1 gene (NF1) is insufficient for astrocytoma formation. Mol Cell Biol 22:5100–5113
Balestri P, Calistri L, Vivarelli R, Bartalini G, Mancini L, Berardi A, Fois A (1993) Central nervous system imaging in reevaluation of patients with neurofibromatosis type 1. Childs Nerv Syst 9:448–451
Blazo MA, Lewis RA, Chintagumpala MM, Frazier M, McCluggage C, Plon SE (2004) Outcomes of systematic screening for optic pathway tumors in children with Neurofibromatosis Type 1. Am J Med Genet A 127:224–229
Dasgupta B, Gutmann DH (2005) Neurofibromin regulates neural stem cell proliferation, survival, and astroglial differentiation in vitro and in vivo. J Neurosci 25:5584–5594
Dasgupta B, Li W, Perry A, Gutmann DH (2005) Glioma formation in neurofibromatosis 1 reflects preferential activation of K-RAS in astrocytes. Cancer Res 65:236–245
Easton D, Ponder M, Huson S, Ponder B (1993) An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes. Am J Hum Genet 53:305–313
Faravelli F, Upadhyaya M, Osborn M, Huson SM, Hayward R, Winter R (1999) Unusual clustering of brain tumours in a family with NF1 and variable expression of cutaneous features. J Med Genet 36:893–896
Friedman JM, Gutmann DH, MacCollin M, Riccardi VM (1999) Neurofibromatosis—phenotype, natural history and pathogenesis. The Johns Hopkins University Press, Baltimore, MD
Friedrich RE, Kluwe L, Funsterer C, Mautner VF (2005) Malignant peripheral nerve sheath tumors (MPNST) in neurofibromatosis type 1(NF1): diagnostic findings on magnetic resonance images and mutation analysis of the NF1 gene. Anticancer Res 25:1699–1702
Griffiths PD, Blaser S, Mukonoweshuro W, Armstrong D, Milo-Mason G, Cheung S (1999) Neurofibromatosis bright objects in children with neurofibromatosis type 1: a proliferative potential? Pediatrics 104:e49
Gutmann DH, James CD, Poyhonen M, Louis DN, Ferner R, Guha A, Hariharan S, Viskochil D, Perry A (2003) Molecular analysis of astrocytomas presenting after age 10 in individuals with NF1. Neurology 61:1397–1400
No authors listed (1995) Health supervision for children with neurofibromatosis. American Academy of Pediatrics Committee on Genetics. Pediatrics 96:368–372
Korf BR (2000) Malignancy in neurofibromatosis type 1. Oncologist 5:477–485
Listernick R, Charrow J, Greenwald M, Mets M (1994) Natural history of optic pathway tumors in children with neurofibromatosis type I: a longitudinal study. J Pediatr 125:63–66
Listernick R, Charrow J, Gutmann DH (1999) Intracranial gliomas in neurofibromatosis type 1. Am J Med Genet 89:38–44
Menor F, Marti-Bonmati L, Mulas F, Cortina H, Olague R (1991) Imaging considerations of central nervous system manifestations in pediatric patients with neurofibromatosis type 1. Pediatr Radiol 21:389–394
Miaux Y, Guermazi A, Cornu P, Mokhtari K, Singer B, Chiras J, Blanchet-Bardon C (1997) High-intensity lesion on T1-weighted MR images in neurofibromatosis type 1: a case of premalignant lesion. Acta Neurochir (Wien) 139:1085–1087
Reddy AT, Wellons JC 3rd (2003) Pediatric high-grade gliomas. Cancer J 9:107–112
Reilly KM, Loisel DA, Bronson RT, McLaughlin ME, Jacks T (2000) Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. Nat Genet 26:109–113
Acknowledgement
The authors would like to thank Mr. C. Fisher, Director Anglo-German Medical Translation Institute (AGMTI), Newcastle upon Tyne, UK, for critically proofreading our manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Distelmaier, F., Fahsold, R., Reifenberger, G. et al. Fatal glioblastoma multiforme in a patient with neurofibromatosis type I: the dilemma of systematic medical follow-up. Childs Nerv Syst 23, 343–347 (2007). https://doi.org/10.1007/s00381-006-0222-4
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00381-006-0222-4