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Neurofibromatosis Type 1 Follow-up

  • Author: David T Hsieh, MD, FAAP; Chief Editor: Amy Kao, MD  more...
Updated: Jul 30, 2015

Further Outpatient Care

Although patients with neurofibromatosis type 1 (NF1) can be cared for in the primary care setting, additional medical concerns need to be addressed on a routine basis.

An outline of reasonable guidelines in caring for patients with NF1 is as follows:

  • Annual examinations should focus on potential complications of NF. Each examination should include blood pressure measurement, assessment of the skin for typical lesions (including early or growing neurofibromas), visual acuity check, evaluation of the eyes for evidence of proptosis or strabismus, and examination of the spine and extremities for any abnormalities. Neurologic evaluation should include a careful history for headaches or motor or sensory symptoms as well as a comprehensive motor and sensory examination.
  • Annual ophthalmologic examinations should check for optic nerve pallor, visual acuity changes, visual field defects, and Lisch nodules. Patients should be referred to an ophthalmologist promptly if the treating physician has any concerns about visual acuity, evidence of proptosis, or a palpebral plexiform neurofibroma obstructing vision.

Further Inpatient Care

Hospitalization may be necessary for major surgical procedures and workup of uncontrolled hypertension.

Many minor surgical procedures (eg, removal of cutaneous neurofibromas) may be done in an outpatient surgical setting.



Complications may include the following:

  • Locally invasive plexiform neurofibromas
  • Optic nerve gliomas, especially in children younger than 5 years
  • Dumbbell-shaped spinal cord neurofibromas or neurofibromas of the brachial or sacral plexus
  • Peripheral neuropathy
  • Scoliosis
  • Hypertension due to pheochromocytoma or renal vascular stenosis secondary to fibromuscular dysplasia
  • Bony modeling defects that may lead to pseudarthrosis, thoracic cage asymmetry, or pathologic fractures
  • Increased risk for brain tumors, leukemia, and other malignancies of neural crest origin (including neurofibrosarcomas and MPNSTs)
  • Learning disabilities, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), or rarely, mental retardation


Although most individuals with NF1 lead relatively long and healthy lives, the overall life expectancy may be reduced by on average 8 years. The major causes for this increased morbidity and subsequent mortality are hypertension, sequelae of spinal cord lesions, and malignancy.

Prompt attention to complications of NF1 and early detection of medical problems may significantly reduce the overall morbidity and mortality rates.


Patient Education

Patients and their families may be referred to NF-specific national and regional support groups for continuous updates on treatment advances and for emotional support. The previous National NF Foundation, Inc, now renamed The Children's Tumor Foundation, has a toll-free telephone number (1-800-323-7938). Parents and families can sign up to receive a newsletter. Neurofibromatosis, Inc is another support and resource group with a toll-free telephone number (1-800-942-6825).

Inform patients of symptoms that would require immediate medical attention, including headaches increasing in intensity or frequency or focal neurological deficits.

Contributor Information and Disclosures

David T Hsieh, MD, FAAP Assistant Professor of Pediatrics, Assistant Professor of Neurology, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Adjunct Assistant Professor of Pediatrics, Adjunct Assistant Professor of Neurology, University of Texas Health Science Center at San Antonio School of Medicine

David T Hsieh, MD, FAAP is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, Child Neurology Society

Disclosure: Nothing to disclose.


Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Kenneth J Mack, MD, PhD Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic

Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, Society for Neuroscience

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock from Cellectar Biosciences; have stock from Varian medical systems; have stock from Express Scripts.

Additional Contributors

Ann M Neumeyer, MD Medical Director, Lurie Center for Autism; Assistant Professor of Neurology, Harvard Medical School; Child Neurologist, Massachusetts General Hospital

Ann M Neumeyer, MD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Massachusetts Medical Society

Disclosure: Nothing to disclose.


The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force, Department of Defense or the U.S. Government.

Beth A Pletcher, MD Associate Professor, Co-Director of The Neurofibromatosis Center of New Jersey, Department of Pediatrics, University of Medicine and Dentistry of New Jersey

Beth A Pletcher, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics

Disclosure: Nothing to disclose.

  1. Garg S, Green J, Leadbitter K, Emsley R, Lehtonen A, Evans DG, et al. Neurofibromatosis Type 1 and Autism Spectrum Disorder. Pediatrics. 2013 Nov 4. [Medline].

  2. Dugoff L, Sujansky E. Neurofibromatosis type 1 and pregnancy. Am J Med Genet. 1996 Dec 2. 66(1):7-10. [Medline].

  3. Darrigo LG Jr, Geller M, Bonalumi Filho A, et al. Prevalence of plexiform neurofibroma in children and adolescents with type I neurofibromatosis. J Pediatr (Rio J). 2007 Nov-Dec. 83(6):571-3. [Medline].

  4. Rodriguez FJ, Perry A, Gutmann DH, et al. Gliomas in neurofibromatosis type 1: a clinicopathologic study of 100 patients. J Neuropathol Exp Neurol. 2008 Mar. 67(3):240-9. [Medline].

  5. Porter DE, Prasad V, Foster L, Dall GF, Birch R, Grimer RJ. Survival in Malignant Peripheral Nerve Sheath Tumours: A Comparison between Sporadic and Neurofibromatosis Type 1-Associated Tumours. Sarcoma. 2009. 2009:756395. [Medline]. [Full Text].

  6. Basile U, Cavallaro G, Polistena A, Giustini S, Orlando G, Cotesta D. Gastrointestinal and Retroperitoneal Manifestations of Type 1 Neurofibromatosis. J Gastrointest Surg. 2009 Jun 3. [Medline].

  7. Hegyi L, Thway K, Newton R, Osin P, Nerurkar A, Hayes AJ. Malignant myoepithelioma arising in adenomyoepithelioma of the breast and coincident multiple gastrointestinal stromal tumours in a patient with neurofibromatosis type 1. J Clin Pathol. 2009 Jul. 62(7):653-5. [Medline].

  8. Yamamoto H, Tobo T, Nakamori M, Imamura M, Kojima A, Oda Y. Neurofibromatosis type 1-related gastrointestinal stromal tumors: a special reference to loss of heterozygosity at 14q and 22q. J Cancer Res Clin Oncol. 2009 Jun. 135(6):791-8. [Medline].

  9. Brunetti-Pierri N, Doty SB, Hicks J, et al. Generalized metabolic bone disease in Neurofibromatosis type I. Mol Genet Metab. 2008 May. 94(1):105-11. [Medline].

  10. Stevenson DA, Schwarz EL, Viskochil DH, et al. Evidence of increased bone resorption in neurofibromatosis type 1 using urinary pyridinium crosslink analysis. Pediatr Res. 2008 Jun. 63(6):697-701. [Medline].

  11. Seitz S, Schnabel C, Busse B, Schmidt HU, Beil FT, Friedrich RE, et al. High bone turnover and accumulation of osteoid in patients with neurofibromatosis 1. Osteoporos Int. 2010 Jan. 21(1):119-27. [Medline].

  12. Tucker T, Schnabel C, Hartmann M, Friedrich RE, Frieling I, Kruse HP. Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1). J Med Genet. 2009 Apr. 46(4):259-65. [Medline].

  13. Smith A, Araoz PA, Kirsch J. Coronary arterial aneurysms in neurofibromatosis 1: case report and review of the literature. J Thorac Imaging. 2009 May. 24(2):129-31. [Medline].

  14. Spurlock G, Bennett E, Chuzhanova N, Thomas N, Jim HP, Side L. SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype. J Med Genet. 2009 Jul. 46(7):431-7. [Medline].

  15. Karagiannis A, Mikhailidis DP, Athyros VG, et al. Pheochromocytoma: an update on genetics and management. Endocr Relat Cancer. 2007 Dec. 14(4):935-56. [Medline].

  16. Lenders JW, Pacak K, Walther MM, et al. Biochemical diagnosis of pheochromocytoma: which test is best?. JAMA. 2002 Mar 20. 287(11):1427-34. [Medline].

  17. Tucker T, Friedman JM, Friedrich RE, Wenzel R, Fünsterer C, Mautner VF. Longitudinal study of neurofibromatosis 1 associated plexiform neurofibromas. J Med Genet. 2009 Feb. 46(2):81-5. [Medline].

  18. Iannicelli E, Rossi G, Almberger M, et al. Integrated imaging in peripheral nerve lesions in type 1 neurofibromatosis. Radiol Med (Torino). 2002 Apr. 103(4):332-43. [Medline].

  19. Matsumine A, Kusuzaki K, Nakamura T, Nakazora S, Niimi R, Matsubara T, et al. Differentiation between neurofibromas and malignant peripheral nerve sheath tumors in neurofibromatosis 1 evaluated by MRI. J Cancer Res Clin Oncol. 2009 Jul. 135(7):891-900. [Medline].

  20. Pacak K, Eisenhofer G, Ahlman H, et al. Pheochromocytoma: recommendations for clinical practice from the First International Symposium. October 2005. Nat Clin Pract Endocrinol Metab. 2007 Feb. 3(2):92-102. [Medline].

  21. Benz MR, Tchekmedyian N, Eilber FC, Federman N, Czernin J, Tap WD. Utilization of positron emission tomography in the management of patients with sarcoma. Curr Opin Oncol. 2009 Jul. 21(4):345-51. [Medline].

  22. Levine E, Huntrakoon M, Wetzel LH. Malignant nerve-sheath neoplasms in neurofibromatosis: distinction from benign tumors by using imaging techniques. AJR Am J Roentgenol. 1987 Nov. 149(5):1059-64. [Medline].

  23. Wojtkowiak JW, Fouad F, LaLonde DT, et al. Induction of apoptosis in neurofibromatosis type 1 malignant peripheral nerve sheath tumor cell lines by a combination of novel farnesyl transferase inhibitors and lovastatin. J Pharmacol Exp Ther. 2008 Jul. 326(1):1-11. [Medline].

  24. Ambrosini G, Cheema HS, Seelman S, et al. Sorafenib inhibits growth and mitogen-activated protein kinase signaling in malignant peripheral nerve sheath cells. Mol Cancer Ther. 2008 Apr. 7(4):890-6. [Medline].

  25. Johansson G, Mahller YY, Collins MH, et al. Effective in vivo targeting of the mammalian target of rapamycin pathway in malignant peripheral nerve sheath tumors. Mol Cancer Ther. 2008 May. 7(5):1237-45. [Medline].

  26. Slomiany MG, Dai L, Bomar PA, Knackstedt TJ, Kranc DA, Tolliver L, et al. Abrogating drug resistance in malignant peripheral nerve sheath tumors by disrupting hyaluronan-CD44 interactions with small hyaluronan oligosaccharides. Cancer Res. 2009 Jun 15. 69(12):4992-8. [Medline].

  27. Hari Kumar KV, Shaikh A, Sandhu AS, Prusty P. Neurofibromatosis 1 with pheochromocytoma. Indian J Endocrinol Metab. 2011 Oct. 15 Suppl 4:S406-8. [Medline]. [Full Text].

  28. Gerszten PC, Burton SA, Ozhasoglu C, et al. Radiosurgery for benign intradural spinal tumors. Neurosurgery. 2008 Apr. 62(4):887-95; discussion 895-6. [Medline].

  29. Bravo EL, Tagle R. Pheochromocytoma: state-of-the-art and future prospects. Endocr Rev. 2003 Aug. 24(4):539-53. [Medline].

  30. AAP Committee on Genetics. Health supervision for children with neurofibromatosis. American Academy of Pediatrics Committee on Genetics. Pediatrics. 1995 Aug. 96(2 Pt 1):368-72. [Medline].

  31. Chander S, Westphal SM, Zak IT, et al. Retroperitoneal malignant peripheral nerve sheath tumor: evaluation with serial FDG-PET. Clin Nucl Med. 2004 Jul. 29(7):415-8. [Medline].

  32. DeClue JE, Cohen BD, Lowy DR. Identification and characterization of the neurofibromatosis type 1 protein product. Proc Natl Acad Sci U S A. 1991 Nov 15. 88(22):9914-8. [Medline].

  33. Deliganis AV, Geyer JR, Berger MS. Prognostic significance of type 1 neurofibromatosis (von Recklinghausen Disease) in childhood optic glioma. Neurosurgery. 1996 Jun. 38(6):1114-8; discussion 1118-9. [Medline].

  34. Denckla MB, Hofman K, Mazzocco MM, et al. Relationship between T2-weighted hyperintensities (unidentified bright objects) and lower IQs in children with neurofibromatosis-1. Am J Med Genet. 1996 Feb 16. 67(1):98-102. [Medline].

  35. Drouet A, Wolkenstein P, Lefaucheur JP, et al. Neurofibromatosis 1-associated neuropathies: a reappraisal. Brain. 2004 Sep. 127:1993-2009. [Medline].

  36. Evans DG, Baser ME, McGaughran J, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002 May. 39(5):311-4. [Medline].

  37. Ferner RE, Hughes RA, Hall SM, et al. Neurofibromatous neuropathy in neurofibromatosis 1 (NF1). J Med Genet. 2004 Nov. 41(11):837-41. [Medline].

  38. Gutmann DH, Collins FS. The neurofibromatosis type 1 gene and its protein product, neurofibromin. Neuron. 1993 Mar. 10(3):335-43. [Medline].

  39. Habiby R, Silverman B, Listernick R, et al. Precocious puberty in children with neurofibromatosis type 1. J Pediatr. 1995 Mar. 126(3):364-7. [Medline].

  40. Hughes RJ, Scoble JE, Reidy JF. Renal angioplasty in non-atheromatous renal artery stenosis: technical results and clinical outcome in 43 patients. Cardiovasc Intervent Radiol. 2004 Sep-Oct. 27(5):435-40. [Medline].

  41. Karadimas P, Hatzispasou E, Bouzas EA. Retinal vascular abnormalities in neurofibromatosis type 1. J Neuroophthalmol. 2003 Dec. 23(4):274-5. [Medline].

  42. Korf BR. Malignancy in neurofibromatosis type 1. Oncologist. 2000. 5(6):477-85. [Medline].

  43. Levy AD, Patel N, Abbott RM, et al. Gastrointestinal stromal tumors in patients with neurofibromatosis: imaging features with clinicopathologic correlation. AJR Am J Roentgenol. 2004 Dec. 183(6):1629-36. [Medline].

  44. Listernick R, Ferner RE, Piersall L, et al. Late-onset optic pathway tumors in children with neurofibromatosis 1. Neurology. 2004 Nov 23. 63(10):1944-6. [Medline].

  45. Nakakura S, Shiraki K, Yasunari T, et al. Quantification and anatomic distribution of choroidal abnormalities in patients with type I neurofibromatosis. Graefes Arch Clin Exp Ophthalmol. 2005 Oct. 243(10):980-4. [Medline].

  46. Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference. Arch Neurol. 1988 May. 45(5):575-8. [Medline].

  47. North KN, Riccardi V, Samango-Sprouse C, et al. Cognitive function and academic performance in neurofibromatosis. 1: consensus statement from the NF1 Cognitive Disorders Task Force. Neurology. 1997 Apr. 48(4):1121-7. [Medline].

  48. Riccardi VM. Neurofibromatosis. Phenotype, Natural History and Pathogenesis. 2nd ed. Johns Hopkins University Press; 1992.

  49. Scott RM, Smith JL, Robertson RL, Madsen JR, Soriano SG, Rockoff MA. Long-term outcome in children with moyamoya syndrome after cranial revascularization by pial synangiosis. J Neurosurg. 2004 Feb. 100(2 Suppl Pediatrics):142-9. [Medline].

  50. Solomon J, Warren K, Dombi E, et al. Automated detection and volume measurement of plexiform neurofibromas in neurofibromatosis 1 using magnetic resonance imaging. Comput Med Imaging Graph. 2004 Jul. 28(5):257-65. [Medline].

  51. Zacharia TT, Jaramillo D, Poussaint TY, et al. MR imaging of abdominopelvic involvement in neurofibromatosis type 1: a review of 43 patients. Pediatr Radiol. 2005 Mar. 35(3):317-22. [Medline].

  52. Zöller M, Rembeck B, Akesson HO, et al. Life expectancy, mortality and prognostic factors in neurofibromatosis type 1. A twelve-year follow-up of an epidemiological study in Göteborg, Sweden. Acta Derm Venereol. 1995 Mar. 75(2):136-40. [Medline].

  53. Listernick R, Ferner RE, Liu, GT, Gutmann DH. Optic pathway gliomas in neurofibromatosis-1: Controversies and recommendations. Ann Neurol. 2007. 61:189-98. [Medline].

  54. Diggs-Andrews KA, Brown JA, Gianino SM, et al. Sex is a major determinant of neuronal dysfunction in neurofibromatosis type 1. Ann Neurol. 2014. 75:309-16. [Medline].

  55. Gutmann DH, Aylsworth A, Carey JC, et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. 1997. 278:51-7. [Medline].

  56. Wilding A, Ingham SL, Lalloo F, et al. Life expectancy in hereditary cancer predisposing diseases: an observational study. J Med Genet. 2012. 49:264–9. [Medline].

  57. Shah KN. The diagnostic and clinical significance of café-au-lait macules. Pediatr Clin North Am. 2010. 57:1131-53. [Medline].

Café-au-lait spots in a 4-year-old boy.
Axillary freckles.
Inguinal freckles.
Multiple neurofibromas in a 28-year-old man.
Plexiform neurofibroma of the right thigh.
Lisch nodules.
Radial and ulnar bowing and obliteration of the intramedullary spaces.
Unidentified bright object (UBO) within the brain parenchyma.
Left optic nerve glioma with thickening of the nerve and proptosis.
Below-the-knee amputation for tibial pseudarthrosis.
The young woman pictured here has a plexiform neurofibroma of the eyelid.
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