Neurofibromatosis 1

  • Rosalie E. Ferner


Neurofibromatosis 1(NF1) is a common autosomal dominant condition that primarily involves the skin and the nervous system.

People with NF1 have an increased risk of developing benign and malignant tumors.


Renal Artery Stenosis Malignant Peripheral Nerve Sheath Tumor Glomus Tumor Plexiform Neurofibroma Primary Progressive Multiple Sclerosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Tilesius von Tilenau WG. Historia pathologica singularis cutis turpitudinis. Jo Godfredi Rheinhardi viri Lannorum. Leipzig, Germany: SL Crusius; 1793.Google Scholar
  2. 2.
    von Recklinghausen FD. über die multiplen fibrome der haut und ihre beziehung zu den multiplen neuromen. A Hirschwald, Berlin; 1882.Google Scholar
  3. 3.
    National Institutes of Health Consensus Development Conference Statement. Neurofibromatosis. Arch Neurol Chicago. 1988;45:575-578.CrossRefGoogle Scholar
  4. 4.
    Huson SM, Compston DAS, Clark P, et al. A genetic study of von Recklinghausen neurofibromatosis in south east Wales. 1. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet. 1989;26:704-711.PubMedCrossRefGoogle Scholar
  5. 5.
    Ferner RE. Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. Lancet Neurol. 2007;6:340-351.PubMedCrossRefGoogle Scholar
  6. 6.
    Ruggieri M, Huson SM. The clinical and diagnostic implications of mosaicism in the neurofibromatoses. J Neurol. 2001;56:1433-1443.Google Scholar
  7. 7.
    Viskochil D, Buchberg AN, Xu G, et al. Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell. 1990;62:1887-1892.CrossRefGoogle Scholar
  8. 8.
    Wallace MR, Marchuk DA, Anderson LB, et al. Type 1 neurofibromatosis gene: identification of a larger transcript disrupted in three NG1 patients. Science. 1990;249:181-186.PubMedCrossRefGoogle Scholar
  9. 9.
    Xu GF, O’Connell P, Viskochil D, et al. The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell. 1990;62:599-608.PubMedCrossRefGoogle Scholar
  10. 10.
    Johannessen CM, Reczek EE, James M, et al. The NF1 tumour suppressor critically regulates TSC2 and mTOR. Proc Natl Acad Sci USA. 2005;102:8573-8578.PubMedCrossRefGoogle Scholar
  11. 11.
    Huson SM, Harper PS, Compston DAS. Von Recklinghausen neurofibromatosis: clinical and population study in south east Wales. Brain. 1988;111:55-81.CrossRefGoogle Scholar
  12. 12.
    Brems H, Chmara M, Sahbatou M, et al. Germline loss of function mutations in SPRED1 cause a neurofibromatosis 1 – like phenotype. Nat Genet. 2007;39:1120-1126.PubMedCrossRefGoogle Scholar
  13. 13.
    Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44:81-88.PubMedCrossRefGoogle Scholar
  14. 14.
    Cambiaghi S, Restano L, Caputo R. Juvenile xanthogranulomas associated with neurofibromatosis 1: 14 patients without evidence of haematologic malignancies. Paediatr Dermatol. 2004;21:97-101.CrossRefGoogle Scholar
  15. 15.
    De Smet L, Sciot R, Legius E. Multifocal glomus tumours of the fingers in two patients with neurofibromatosis type 1. J Med Genet. 2002;39:e45.PubMedCrossRefGoogle Scholar
  16. 16.
    Schindeler A, Little DG. Recent insights into bone development, homeostasis, and repair in type 1 neurofibromatosis (NF1). Bone. 2008;42:616-622.PubMedCrossRefGoogle Scholar
  17. 17.
    Ferner RE. The neurofibromatoses. Pract Neurol. 2010;10:82-93.PubMedCrossRefGoogle Scholar
  18. 18.
    Crawford AH Jr, Bagamery N. Osseous manifestations of neurofibromatosis in childhood. J Pediatr Orthop. 1986;6:72-88.PubMedCrossRefGoogle Scholar
  19. 19.
    Cnossen MH, Moons KG, Garssen MP, et al. Minor disease features in neurofibromatosis type 1 (NF1) and their possible value in diagnosis of NF1 in children < or =6 years and clinically suspected of having NF1. Neurofibromatosis team of Sophia Children’s Hospital. J Med Genet. 1998;35:624-627.PubMedCrossRefGoogle Scholar
  20. 20.
    Tucker T, Schnabel C, Hartmann M, et al. Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1). J Med Genet. 2009;46:259-265.PubMedCrossRefGoogle Scholar
  21. 21.
    Howlett DC, Farrugia MM, Ferner RE, et al. Multiple lower limb non-ossifying neurofibromas in siblings with neurofibromatosis. Eur J Radiol. 1998;26:280-283.PubMedCrossRefGoogle Scholar
  22. 22.
    Casselman ES, Mandell GA. Vertebral scalloping in neurofibromatosis. Radiology. 1979;131:89-94.PubMedGoogle Scholar
  23. 23.
    Kimura M, Kamata Y, Matsumoto K, et al. Electron microscopical study on the tumour of von Recklinghausen’s neurofibromatosis. Acta Pathol Jpn. 1974;24:79-91.PubMedGoogle Scholar
  24. 24.
    Lammert M, Mautner VF, Kluwe L. Do hormonal contraceptives stimulate growth of neurofibromas? A survey on 59 NF1 patients. BMC Cancer. 2005;5:16.PubMedCrossRefGoogle Scholar
  25. 25.
    Evans DGR, Huson S, Donnai D, et al. A clinical study of type 2 neurofibromatosis. Q J Med. 1992;84:603-618.PubMedGoogle Scholar
  26. 26.
    MacCollin M, Chiocca EA, Evans DG, et al. Diagnostic criteria for Schwannomatosis. Neurology. 2005;64:1838-1845.PubMedCrossRefGoogle Scholar
  27. 27.
    Sharif S, Moran A, Huson SM, et al. Women with neurofibromatosis 1 are at a moderately increased risk of developing breast cancer and should be considered for early screening. J Med Genet. 2007;44:481-484.PubMedCrossRefGoogle Scholar
  28. 28.
    Leonard JR, Ferner RE, Thomas N, et al. Cervical cord compression from plexiform neurofibromas in neurofibromatosis 1. J Neurol Neurosurg Psychiatry. 2007;78:1404-1406.PubMedCrossRefGoogle Scholar
  29. 29.
    Mautner VF, Asuagbor FA, Dombi E, et al. Assessment of benign tumour burden by whole-body MRI in patients with neurofibromatosis 1. Neuro Oncol. 2008;10:593-598.PubMedCrossRefGoogle Scholar
  30. 30.
    Evans DG, Baser ME, McGraughran J, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002;39:311-314.PubMedCrossRefGoogle Scholar
  31. 31.
    Ferner RE, Gutmann D. International Consensus Group Statement of the management of malignant peripheral nerve sheath tumours in neurofibromatosis 1. Cancer Res. 2002;62:1573-1577.PubMedGoogle Scholar
  32. 32.
    Ferner RE, Golding JF, Smith M, et al. [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a diagnostic tool for neurofibromatosis 1 (NF1) associated malignant peripheral nerve sheath tumours (MPNSTs): a long-term clinical study. Ann Oncol. 2008;19:390-394.PubMedCrossRefGoogle Scholar
  33. 33.
    Ferner RE, Hughes RA, Hall SM, et al. Neurofibromatous neuropathy in neurofibromatosis 1 (NF1). J Med Genet. 2004;41:837-841.PubMedCrossRefGoogle Scholar
  34. 34.
    North K, Riccardi V, Samango-Sprouse C, et al. Cognitive function and academic performance in NF1: consensus statement from the NF1 cognitive disorders task force. Neurology. 1997;48:1121-1127.PubMedCrossRefGoogle Scholar
  35. 35.
    Costa RM, Silva AJ. Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1. J Child Neurol. 2002;17:622-626.PubMedCrossRefGoogle Scholar
  36. 36.
    Krab LC, de Goede-Bolder A, Aarsen FK, et al. Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: a randomised controlled trial. JAMA. 2008;300:287-294.PubMedCrossRefGoogle Scholar
  37. 37.
    Créange A, Zeller J, Rostaing-Rigattieri S, et al. Neurological complications of neurofibromatosis type 1 in adulthood. Brain. 1999;122:473-481.PubMedCrossRefGoogle Scholar
  38. 38.
    Gill DS, Hyman SL, Steinberg A, North KN. Age-related findings on MRI in neurofibromatosis type 1. Pediatr Radiol. 2006;36:1048-1056.PubMedCrossRefGoogle Scholar
  39. 39.
    Hyman SL, Gill DS, Shores EA, et al. T2 hyperintensities in children with neurofibromatosis type 1 and their relationship to cognitive functioning. J Neurol Neurosurg Psychiatry. 2007;78:1088-1091.PubMedCrossRefGoogle Scholar
  40. 40.
    Listernick R, Ferner RE, Liu GT, et al. Optic pathway gliomas in neurofibromatosis-1: controversies and recommendations. Ann Neurol. 2007;61:189-198.PubMedCrossRefGoogle Scholar
  41. 41.
    Listernick R, Ferner RE, Piersall L, et al. Late-onset optic pathway tumours in children with neurofibromatosis 1. Neurology. 2004;63:194-196.CrossRefGoogle Scholar
  42. 42.
    Sharif S, Ferner R, Birch JM, et al. Second primary tumours in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy. J Clin Oncol. 2006;24:2570-2575.PubMedCrossRefGoogle Scholar
  43. 43.
    Packer RJ, Alter J, Allen J, et al. Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg. 1997;86:747-754.PubMedCrossRefGoogle Scholar
  44. 44.
    Dasgupta B, Yi Y, Chen DY, et al. Proteomic analysis reveals hyper-activation of the mammalian target of rapacmycin pathway in neurofibromatosis 1-associated human and mouse brain tumours. Cancer Res. 2005;1:2755-2760.CrossRefGoogle Scholar
  45. 45.
    Schonauer C, Tessitore E, Frascadore L, et al. Lumbosacral dural ectasia in type 1 neurofibromatosis. Report of two cases. Neurosurg Sci. 2000;44:165-168.Google Scholar
  46. 46.
    Vivarelli R, Grosso S, Calabrese F. Epilepsy in neurofibromatosis 1. J Child Neurol. 2003;18:338-342.PubMedCrossRefGoogle Scholar
  47. 47.
    Johnson MR, Ferner RE, Bobrow M, et al. Detailed analysis of the oligodendrocyte myelin glycoprotein gene in four patients with neurofibromatosis 1 and primary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry. 2000;8:643-646.CrossRefGoogle Scholar
  48. 48.
    Rea D, Brandsema JF, Armstrong D. Cerebral arteriopathy in children with neurofibromatosis type 1. Pediatrics. 2009;124:e476-e483.PubMedCrossRefGoogle Scholar
  49. 49.
    Rosser TL, Vezina G, Packer RT. Cerebrovascular abnormalities in a population of children with neurofibromatosis type 1. Neurology. 2005;64:553-555.PubMedCrossRefGoogle Scholar
  50. 50.
    Friedman JM, Arbiser J, Epstein JA, et al. Cardiovascular disease in neurofibromatosis 1: a report of the NF1 Cardiovascular Task Force. Genet Med. 2003;4:105-111.CrossRefGoogle Scholar
  51. 51.
    Lisch K. Ueber beteiligung der augen, insbesondere das vorkommen von irisknotchen bei der neurofibromatose (Recklinghausen). Z Augenheilkunde. 1937;93:137-143.Google Scholar
  52. 52.
    Srinivasan A, Krishnamurthy G, Fontalvo-Herazo L, et al. Spectrum of renal findings in paediatric fibromuscular dysplasia and neurofibromatosis type 1. Pediatr Radiol. 2010 Oct 16. Epub ahead of print.Google Scholar
  53. 53.
    Bausch B, Borozdin W, Neumann H, et al. Clinical and genetic characteristics of patients with neurofibromatosis type 1 and phaeochromocytoma. NEJM. 2006;354:2729-2731.PubMedCrossRefGoogle Scholar
  54. 54.
    Miettinen M, Fetsch JF, Sobin LH, et al. Gastrointestinal stromal tumours in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol. 2006;30:90-96.PubMedCrossRefGoogle Scholar
  55. 55.
    Hough DR, Usar MC, Chan A, et al. Von Recklinghausen’s disease associated with gastrointestinal carcinoid tumours. Cancer. 1983;51:2206-2208.PubMedCrossRefGoogle Scholar
  56. 56.
    Verlinsky Y, Rechitsky S, Verlinsky O, et al. Preimplantation diagnosis for neurofibromatosis. Reprod Biomed Online. 2002;4:218-222.PubMedCrossRefGoogle Scholar
  57. 57.
    Maertens O, De Schepper S, Vandesompele J, et al. Molecular dissection of isolated disease features in mosaic neurofibromatosis type 1. Am J Hum Genet. 2007;81:243-251.PubMedCrossRefGoogle Scholar
  58. 58.
    Upadhyaya M. Neurofibromatosis type 1: diagnosis and recent advances. Expert Opin Med Diagn. 2010;4:307-322.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2011

Authors and Affiliations

  • Rosalie E. Ferner
    • 1
    • 2
  1. 1.Department of NeurologyGuy’s and St. Thomas’ NHS Foundation TrustLondonUK
  2. 2.Department of Clinical Neuroscience, Institute of PsychiatryKing’s CollegeLondonUK

Personalised recommendations