Neurofibromatosis: From Genes to Complications to Treatments

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The 2008 NF Conference was held last weekend (June 6 — 10) in Bonita Springs, Florida. The preeminent annual meeting provides a forum for basic and clinical neurofibromatosis (NF) investigators to present their research (pronounced noor-oh-fahy-broh-muh-toh-sis). The conference was attended by over 200 researchers from around the world


This year’s theme — Genes to Complications to Treatments — highlighted the progress being made in NF research and clinical care, as well as the research programs of the Children’s Tumor Foundation. Last year’s NF Conference focused on models, mechanisms and therapeutic targets.

The neurofibromatoses are familial cancer syndromes that predispose individuals to the development of a variety of benign and malignant tumors in the central and peripheral nervious systems. The disorders cause tumors to grow along various types of nerves and can also affect the development of bones and skin. Neurofibromatosis has been classified into three distinct types:

  • Neurofibromatosis type 1 (NF1) occurs in 1:3,500 births and is caused by a mutation of the NF1 gene on chromosome 17q11.2. NF1 diagnostic criteria (two or more) include cafe-au-lait macules, freckling, optic glioma, Lisch nodules, bony abnormalities, a first-degree relative with NF1, two or more benign nerve sheath tumors (neurofibromas) of any type, or at least one plexiform neurofibroma [1-2].
    At least 95% of NF1 patients develop benign tumors called neurofibromas [3], which may be disfiguring or associated with pain and neurological defect. As there is no cure for neurofibromatosis, the only therapy is surgical removal of the tumor and associated nerve. Approximately 6 — 13% of NF1 patients will progress and develop a malignant peripheral nerve sheath tumor (MPNST), an aggressive sarcoma that has a high mortality rate (~ 50%) [4].

  • Neurofibromatosis type 2 (NF2) occurs in 1:25,000 births and is caused by a mutation of the NF2 gene on chromosome 22q12. Ninety percent of NF2 patients develop bilateral vestibular schwannomas and/or spinal schwannomas. Enlarging schwannomas can compress adjacent structures, resulting in deafness or other neurologic deficits depending on their location. Surgical removal of these tumors is difficult, often resulting in patient morbidity. Although 95% of schwannomas occur sporadically, multiple schwannomas are the hallmark of inherited NF2 [5].

  • Schwannomatosis occurs in 1:40,000 patients and, in contrast to NF2, develop multiple peripheral schwannomas, but not schwannomas of the vestibular nerve. Schwannomas in schwannomatosis patients are often associated with severe, intractable neuropathic pain and sometimes numbness, tingling and weakness. It was believed that a germline mutation in an unidentified gene predisposes patients to NF2 mutation [6]. Recently, the INI1 gene was identified as a possible schwannomatosis gene [7-8].

Both NF1 and NF2 are tumor suppressor genes.

The Children’s Tumor Foundation (CTF) is dedicated to ending neurofibromatosis through research. The CTF has funded NF research for over 25 years with the goal of identifying NF drug therapies and improving the lives of those living with the disorder. The Foundation also endeavors to increase public awareness of NF and provides resources for NF patients and their families.

For more information on NF, visit the Children’s Tumor Foundation and Neurofibromatosis Cafe.

CTF medical podcasts are also available.


  1. Riccardi VM. The prenatal diagnosis of NF-1 and NF-2. J Dermatol. 1992 Nov;19(11):885-91.
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  2. Gutmann et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. 1997 Jul 2;278(1):51-7.
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  3. Rasmussen and Friedman. NF1 gene and neurofibromatosis 1. Am J Epidemiol. 2000 Jan 1;151(1):33-40.
    View abstract
  4. Evans et al. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002 May;39(5):311-4.
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  5. Evans et al. A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity. J Med Genet. 1992 Dec;29(12):841-6.
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  6. Jacoby et al. Molecular analysis of the NF2 tumor-suppressor gene in schwannomatosis. Am J Hum Genet. 1997 Dec;61(6):1293-302.
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  7. Hulsebos et al. Germline mutation of INI1/SMARCB1 in familial schwannomatosis. Am J Hum Genet. 2007 Apr;80(4):805-10. Epub 2007 Feb 16.
    View abstract
  8. Hadfield et al. Molecular characterisation of SMARCB1 and NF2 in familial and sporadic schwannomatosis. J Med Genet. 2008 Jun;45(6):332-9. Epub 2008 Feb 19.
    View abstract
About the Author

Walter Jessen, Ph.D. is a Data Scientist, Digital Biologist, and Knowledge Engineer. His primary focus is to build and support expert systems, including AI (artificial intelligence) and user-generated platforms, and to identify and develop methods to capture, organize, integrate, and make accessible company knowledge. His research interests include disease biology modeling and biomarker identification. He is also a Principal at Highlight Health Media, which publishes Highlight HEALTH, and lead writer at Highlight HEALTH.