Journal of Genetic Counseling

, Volume 27, Issue 5, pp 1102–1110 | Cite as

Health Survey of Adults with Neurofibromatosis 1 Compared to Population Study Controls

  • Krister W. FjermestadEmail author
  • Livø Nyhus
  • Øivind J. Kanavin
  • Arvid Heiberg
  • Lise B. Hoxmark
Original Research


Neurofibromatosis type 1 (NF1) is a genetic, autosomal dominant multi-organ disease characterized by susceptibility to tumor formation, changes in skin pigmentation, skeletal abnormalities, and neuropsychological deficits. Clinical studies have shown impaired health-related quality of life (HQoL) in adults with NF1. However, little is known about HQoL in non-clinical NF1 samples. We conducted a cross-sectional self-report survey of 142 persons with NF1 (M age = 50.3 years, SD = 12.0, range 32 to 80; 62.0% females) recruited from non-clinical settings. Several HQoL domains, including life satisfaction, mental health, sleep, pain, gastrointestinal problems, oral health, and social support, were compared between the NF1 sample and 46,293 controls from the HUNT3 population study. We also examined gender differences within the NF1 sample and predictors of HQoL. Compared to controls, the NF1 sample reported significantly poorer life satisfaction, mental health, sleep, and oral health, and more pain, gastrointestinal problems, comorbid diseases, and memory problems. Several HQoL domains were significantly correlated. Mental health was the only unique significant predictor of overall life satisfaction. Women with NF1 reported significantly more mental health, sleep, and pain problems than men with NF1. Mental health assessment and management should be integrated into clinical care of persons with NF1 to potentially improve their HQoL.


Neurofibromatosis NF1 Quality of life Mental health 



We would like to thank the Norwegian Union for Neurofibromatosis, Eva Elisabeth Næss, and Grete Hummelvoll for their help with design and data collection.

Compliance with Ethical Standards

Conflict of Interest

K.W.F., L.N., Ø.J.K., A.H., and L.B.H. declare that they have no conflict of interest.

Human Studies and Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

Animal Studies

This article does not contain any studies with animals performed by any of the authors.


  1. Abramowicz, A., & Gos, M. (2014). Neurofibromin in neurofibromatosis type 1—mutations in NF1gene as a cause of disease. Developmental Period Medicine, 18(3), 297–306.PubMedGoogle Scholar
  2. Agaimy, A., Vassos, N., & Croner, R. S. (2012). Gastrointestinal manifestations of neurofibromatosis type 1 (Recklinghausen’s disease): clinicopathological spectrum with pathogenetic considerations. International Journal of Clinical and Experimental Pathology, 5(9), 852–862.PubMedPubMedCentralGoogle Scholar
  3. Barton, B., & North, K. (2004). Social skills of children with neurofibromatosis type 1. Developmental Medicine and Child Neurology, 46(8), 553–563. CrossRefPubMedGoogle Scholar
  4. Bicudo, N. P., de Menezes Neto, B. F., da Silva de Avo, L. R., Ramos Germano, C. M., & Melo, D. G. (2016). Quality of life in adults with neurofibromatosis 1 in Brazil. Journal of Genetic Counseling, 25(5), 1063–1074. CrossRefPubMedGoogle Scholar
  5. Birch, P., & Friedman, J. M. (2012). Quality of life in NF1. In M. Upadhyaya & D. N. Cooper (Eds.), Neurofibromatosis type 1 (pp. 93–103). Berlin: Springer-Verlag.CrossRefGoogle Scholar
  6. Cosyns, M., Mortier, G., Janssens, S., & Van Borsel, J. (2012). Voice-related quality of life in adults with neurofibromatosis type 1. Journal of Voice, 26(2), E57–E62. CrossRefPubMedGoogle Scholar
  7. Crawford, H. A., Barton, B., Wilson, M. J., Berman, Y., McKelvey-Martin, V. J., Morrison, P. J., & North, K. N. (2015). The impact of neurofibromatosis type 1 on the health and wellbeing of Australian adults. Journal of Genetic Counseling, 24(6), 931–944. CrossRefPubMedGoogle Scholar
  8. Descheemaeker, M. J., Ghesquiere, P., Symons, H., Fryns, J. P., & Legius, E. (2005). Behavioural, academic and neuropsychological profile of normally gifted neurofibromatosis type 1 children. Journal of Intellectual Disability Research, 49, 33–46. CrossRefPubMedGoogle Scholar
  9. Descheemaeker, M. J., Plasschaert, E., Fryns, J. P., & Legius, E. (2013). Neuropsychological profile in adults with neurofibromatosis type 1 compared to a control group. Journal of Intellectual Disability Research, 57(9), 874–886. CrossRefPubMedGoogle Scholar
  10. Ejerskov, C., Krogh, K., Ostergaard, J. R., Fassov, J. L., & Haagerup, A. (2017). Constipation in adults with neurofibromatosis type 1. Orphanet Journal of Rare Diseases, 12(1), 139. CrossRefPubMedPubMedCentralGoogle Scholar
  11. Ejerskov, C., Lasgaard, M., & Ostergaard, J. R. (2015). Teenagers and young adults with neurofibromatosis type 1 are more likely to experience loneliness than siblings without the illness. Acta Paediatrica, 104(6), 604–609. CrossRefPubMedGoogle Scholar
  12. Ferner, R. E., & Gutmann, D. H. (2013). Neurofibromatosis type 1 (NF1): diagnosis and management. Handbook of Clinical Neurology, 115, 939–955. CrossRefPubMedGoogle Scholar
  13. Ferner, R. E., Hughes, R. A. C., & Weinman, J. (1996). Intellectual impairment in neurofibromatosis 1. Journal of the Neurological Sciences, 138(1–2), 125–133. CrossRefPubMedGoogle Scholar
  14. Ferner, R. E., Thomas, M., Mercer, G., Williams, V., Leschziner, G. D., Afridi, S. K., & Golding, J. F. (2017). Evaluation of quality of life in adults with neurofibromatosis 1 (NF1) using the impact of NF1 on quality of life (INF1-QOL) questionnaire. Health and Quality of Life Outcomes, 15, 34. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Granstroem, S., Langenbruch, A., Augustin, M., & Mautner, V. F. (2012). Psychological burden in adult neurofibromatosis type 1 patients: impact of disease visibility on body image. Dermatology, 224(2), 160–167. CrossRefGoogle Scholar
  16. Howell, S. J., Hockenhull, K., Salih, Z., & Evans, D. G. (2017). Increased risk of breast cancer in neurofibromatosis type 1: current insights. Breast Cancer (Dove Med Press), 9, 531–536. CrossRefGoogle Scholar
  17. Hyman, S. L., Shores, A., & North, K. N. (2005). The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology, 65(7), 1037–1044. CrossRefPubMedGoogle Scholar
  18. Javed, F., Ramalingam, S., Ahmed, H. B., Gupta, B., Sundar, C., Qadri, T, … & Romanos, G. E. (2014). Oral manifestations in patients with neurofibromatosis type-1: a comprehensive literature review. Critical Reviews in Oncology Hematology, 91(2), 123–129. doi: Scholar
  19. Kodra, Y., Giustini, S., Divona, L., Porciello, R., Calvieri, S., Wolkenstein, P., & Taruscio, D. (2009). Health-related quality of life in patients with neurofibromatosis type 1. Dermatology, 218(3), 215–220. CrossRefPubMedGoogle Scholar
  20. Kresak, J. L., & Walsh, M. (2016). Neurofibromatosis: a review of NF1, NF2, and schwannomatosis. Journal of Pediatric Genetics, 5(2), 98–104. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Krokstad, S., Langhammer, A., Hveem, K., Holmen, T. L., Midthjell, K., Stene, T. R., Bratberg, G., Heggland, J., & Holmen, J. (2013). Cohort profile: The HUNT study, Norway. International Journal of Epidemiology, 42(4), 968–977. CrossRefPubMedGoogle Scholar
  22. Leschziner, G. D., Golding, J. F., & Ferner, R. E. (2013). Sleep disturbance as part of the neurofibromatosis type 1 phenotype in adults. American Journal of Medical Genetics Part A, 161A(6), 1319–1322. CrossRefPubMedGoogle Scholar
  23. Mannsverk, J., Wilsgaard, T., Njølstad, I., Hopstock, L. A., Løchen, M.-L., Mathiesen, E. B., Thelle, D. S., Rasmussen, K., & Bønaa, K. H. (2012). Age and gender differences in incidence and case fatality trends for myocardial infarction: a 30-year follow-up. The Tromsø study. European Journal of Preventive Cardiology, 19(5), 927–934. CrossRefPubMedGoogle Scholar
  24. Mautner, V. F., Kluwe, L., Thakker, S. D., & Leark, R. A. (2002). Treatment of ADHD in neurofibromatosis type 1. Developmental Medicine and Child Neurology, 44(3), 164–170. CrossRefPubMedGoogle Scholar
  25. Melchiorre, M. G., Chiatti, C., Lamura, G., Torres-Gonzales, F., Stankunas, M., Lindert, J., … & Soares, J. (2013). Social support, socio-economic status, health and abuse among older people in seven European countries. PLoS One, 8(1):e54856.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Michelson, H., Bolund, C., Nilsson, B., & Brandberg, Y. (2000). Health-related quality of life measured by the EORTC QLQ-C30—reference values from a large sample of the Swedish population. Acta Oncologica, 39(4), 477–484.CrossRefPubMedGoogle Scholar
  27. Mong, J. A., & Cusmano, D. M. (2016). Sex differences in sleep: impact of biological sex and sex steroids. Philosophical Transactions of the Royal Society B-Biological Sciences, 371 (1688). doi: Scholar
  28. Nelson, J. P. (2014). Gender differences in alcohol demand: a systematic review of the role of prices and taxes. Health Economics, 23(10), 1260–1280. CrossRefPubMedGoogle Scholar
  29. Nutakki, K., Hingtgen, C. M., Monahan, P., Varni, J. W., & Swigonski, N. L. (2013). Development of the Adult PedsQL (TM) neurofibromatosis type 1 module: initial feasibility, reliability and validity. Health and Quality of Life Outcomes, 11. doi: Scholar
  30. Ostendorf, A. P., Gutmann, D. H., & Weisenberg, J. L. Z. (2013). Epilepsy in individuals with neurofibromatosis type I. Epilepsia, 54(10), 1810–1814. CrossRefPubMedGoogle Scholar
  31. Page, P. Z., Page, G. P., Ecosse, E., Korf, B. R., Leplege, A., & Wolkenstein, P. (2006). Impact of neurofibromatosis 1 on quality of life: a cross-sectional study of 176 American cases. American Journal of Medical Genetics Part A, 140A(18), 1893–1898. CrossRefGoogle Scholar
  32. Pinkerton, K. E., Harbaugh, M., Han, M. K., Jourdan Le Saux, C., Van Winkle, L. S., Martin, W. J., … George, M. (2015). Women and lung disease. Sex differences and global health disparities. American Journal of Respiratory and Critical Care Medicine, 192(1), 11–16. doi: Scholar
  33. Rosnau, K., Hashmi, S. S., Northrup, H., Slopis, J., Noblin, S., & Ashfaq, M. (2017). Knowledge and self-esteem of individuals with neurofibromatosis type 1 (NF1). Journal of Genetic Counseling, 26(3), 620–627. CrossRefPubMedGoogle Scholar
  34. Schmulson, M., Adeyemo, M., Gutierrez-Reyes, G., Charua-Guindic, L., Farfan-Labonne, B., … & Chang, L. (2010). Differences in gastrointestinal symptoms according to gender in Rome II positive IBS and dyspepsia in a Latin American population. American Journal of Gastroenterology, 105:925–932; doi: Scholar
  35. Shapiro, S. D., Abramovitch, K., Van Dis, M. L., Skoczylas, L. J., Langlais, R. P., Jorgenson, R. J., …, & Riccardi, V. M. (1984). Neurofibromatosis: oral and radiographic manifestations. Oral Surgery Oral Medicine and Oral Pathology, 58, 493–498.CrossRefPubMedGoogle Scholar
  36. Shino, M. Y., Rabbani, S., Belperio, J. A., Lynch, J. P., & Weigt, S. S. (2012). Neurofibromatosis-associated diffuse lung disease: case report. Seminars in Respiratory and Critical Care Medicine, 33(5), 572–575. CrossRefPubMedGoogle Scholar
  37. Vranceanu, A. M., Merker, V. L., Park, E., & Plotkin, S. R. (2013). Quality of life among adult patients with neurofibromatosis 1, neurofibromatosis 2 and schwannomatosis: a systematic review of the literature. Journal of Neuro-Oncology, 114(3), 257–262. CrossRefPubMedGoogle Scholar
  38. Williams, V. C., Lucas, J., Babcock, M. A., Gutmann, D. H., Korf, B., & Maria, B. L. (2009). Neurofibromatosis type 1 revisited. Pediatrics, 123(1), 124–133. CrossRefPubMedGoogle Scholar
  39. Wolkenstein, P., Zeller, J., Revuz, J., Ecosse, E., & Leplege, A. (2001). Quality-of-life impairment in neurofibromatosis type 1—a cross-sectional study of 128 cases. Archives of Dermatology, 137(11), 1421–1425.CrossRefPubMedGoogle Scholar
  40. Zöller, M., Rembeck, B., & Backman, L. (1997). Neuropsychological deficits in adults with neurofibromatosis type 1. Acta Neurologica Scandinavica, 95(4), 225–232.CrossRefPubMedGoogle Scholar

Copyright information

© National Society of Genetic Counselors, Inc. 2018

Authors and Affiliations

  • Krister W. Fjermestad
    • 1
    • 2
    Email author
  • Livø Nyhus
    • 1
  • Øivind J. Kanavin
    • 1
  • Arvid Heiberg
    • 3
  • Lise B. Hoxmark
    • 1
  1. 1.Frambu Resource Centre for Rare DisordersSiggerudNorway
  2. 2.Department of PsychologyUniversity of OsloOsloNorway
  3. 3.Department of Medical GeneticsOslo University HospitalOsloNorway

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