Child's Nervous System

, Volume 23, Issue 3, pp 343–347

Fatal glioblastoma multiforme in a patient with neurofibromatosis type I: the dilemma of systematic medical follow-up

  • Felix Distelmaier
  • Raimund Fahsold
  • Guido Reifenberger
  • Martina Messing-Juenger
  • Jörg Schaper
  • Dominik T. Schneider
  • Ulrich Göbel
  • Ertan Mayatepek
  • Thorsten Rosenbaum
Case Report



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 developing 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)].


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.


Children Follow-up MRI Glioblastoma multiforme Neurofibromatosis type I Novel NF1 mutation 


  1. 1.
    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 22:5100–5113PubMedCrossRefGoogle Scholar
  2. 2.
    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 9:448–451PubMedCrossRefGoogle Scholar
  3. 3.
    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 127:224–229PubMedCrossRefGoogle Scholar
  4. 4.
    Dasgupta B, Gutmann DH (2005) Neurofibromin regulates neural stem cell proliferation, survival, and astroglial differentiation in vitro and in vivo. J Neurosci 25:5584–5594PubMedCrossRefGoogle Scholar
  5. 5.
    Dasgupta B, Li W, Perry A, Gutmann DH (2005) Glioma formation in neurofibromatosis 1 reflects preferential activation of K-RAS in astrocytes. Cancer Res 65:236–245PubMedGoogle Scholar
  6. 6.
    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 53:305–313PubMedGoogle Scholar
  7. 7.
    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 36:893–896PubMedGoogle Scholar
  8. 8.
    Friedman JM, Gutmann DH, MacCollin M, Riccardi VM (1999) Neurofibromatosis—phenotype, natural history and pathogenesis. The Johns Hopkins University Press, Baltimore, MDGoogle Scholar
  9. 9.
    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 25:1699–1702PubMedGoogle Scholar
  10. 10.
    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:e49PubMedCrossRefGoogle Scholar
  11. 11.
    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 61:1397–1400PubMedGoogle Scholar
  12. 12.
    No authors listed (1995) Health supervision for children with neurofibromatosis. American Academy of Pediatrics Committee on Genetics. Pediatrics 96:368–372Google Scholar
  13. 13.
    Korf BR (2000) Malignancy in neurofibromatosis type 1. Oncologist 5:477–485PubMedCrossRefGoogle Scholar
  14. 14.
    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 125:63–66PubMedCrossRefGoogle Scholar
  15. 15.
    Listernick R, Charrow J, Gutmann DH (1999) Intracranial gliomas in neurofibromatosis type 1. Am J Med Genet 89:38–44PubMedCrossRefGoogle Scholar
  16. 16.
    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 21:389–394PubMedCrossRefGoogle Scholar
  17. 17.
    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) 139:1085–1087CrossRefGoogle Scholar
  18. 18.
    Reddy AT, Wellons JC 3rd (2003) Pediatric high-grade gliomas. Cancer J 9:107–112PubMedCrossRefGoogle Scholar
  19. 19.
    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 26:109–113PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Felix Distelmaier
    • 1
  • Raimund Fahsold
    • 2
  • Guido Reifenberger
    • 3
  • Martina Messing-Juenger
    • 4
  • Jörg Schaper
    • 5
  • Dominik T. Schneider
    • 6
  • Ulrich Göbel
    • 6
  • Ertan Mayatepek
    • 1
  • Thorsten Rosenbaum
    • 1
  1. 1.Department of General Pediatrics, University Children’s HospitalHeinrich-Heine-University DüsseldorfDüsseldorfGermany
  2. 2.Gemeinschaftspraxis B. Prager & A. JungeDresdenGermany
  3. 3.Institute of NeuropathologyHeinrich-Heine-UniversityDüsseldorfGermany
  4. 4.Department of NeurosurgeryHeinrich-Heine-UniversityDüsseldorfGermany
  5. 5.Department of Diagnostic RadiologyHeinrich-Heine-UniversityDüsseldorfGermany
  6. 6.Department of Pediatric Oncology, Hematology and ImmunologyHeinrich-Heine-UniversityDüsseldorfGermany

Personalised recommendations