Neurofibromatose 1

Zuletzt aktualisiert: 2020-06-18

Autor(en): Anzengruber, Navarini

ICD11: LD2D.10

Von Recklinghausen 1882

Periphere Neurofibromatose, Neurofibromatosis generalisata, Morbus Recklinghausen, NF, NF-1.

Autosomal-dominant vererbte neuroektodermale Systemerkrankung.

  • Inzidenz: Ca. 1/3'000 Lebendgeburten.
  • Männer > Frauen.
  • Defekt des NF-1-Gens (17q11.2)
  • Autosomal-dominante Vererbung
  • Fast 100%ige Penetranz
  • Neumutationen kommen in ca. 50% der Fälle vor.
  • Café-au-lait-Flecken
  • Hyperpigmentierungen axillär, inguinal, manchmal auch im Bereich der Mundschleimhaut.
  • Neurofibrome mit Klingelknopfphänomen: Exophytische wachsende, subkutane Hautläsionen lassen sich auf Druck unter das Hautniveau schieben und kommen dann wieder hervor.

≥2 Kriterien müssen für eine Diagnose erfüllt sein:

  1. ≥ 6 Café-au-lait-Flecken
    1. Ø vor der Pubertät ≥ 0,5 cm
    2. Ø nach der Pubertät ≥ 1,5 cm
  2. ≥ 2 Neurofibrome jedes Types oder 1 plexiformes Neurofibrom
  3. Pigmentierungen axillär oder inguinal
  4. ≥ 2 Lisch-Knötchen
  5. Optikusgliom
  6. Ossäre Veränderungen z.B.
    1. Keilbeinflügeldysplasie
    2. Verdünnung der langen Röhrenknochen (Rarefikation) +/- Pseudoarthrose
  7. Verwandter 1. Grades (Eltern, Geschwister oder Kinder) mit NF-1.
  • ZNS:
    • Neurologische Symptomatiken bei Auftreten in Spinal- und Hirnnervenwurzeln
      • Tumore
        • Meningeome
        • Astrozytome
        • Optikusgliom
      • Lernbehinderungen
      • Geistige Retardierung
      • Epilepsie
      • Hirndruck-Symptomatik 
  • Auge
    • Lisch-Knötchen
  • Skelett
    • Skoliose
    • Tibiapseudarthorse
    • Kelbeinflügeldysplasie
  • Endokrine Störungen
    • Selten Phäochromozytom
    • Hypophysen-Tumor
  • Maligne Tumore
    • CML
    • Nervenscheiden-Tumore
  • Chirurgische Exzision von Tumoren
  • Dermatologische Untersuchungen sollten 1x jährlich stattfinden.
  • Genetische Beratung
  • Pränatale Diagnostik
  • Kontrollen in anderen Kliniken
    • Neurologie
    • Augenheilkunde
    • HNO
  1. Neurofibromatosis. Arch Neurol, 1988. 45(5): p. 575.
  2. Brems, H., et al., Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1–like phenotype. Nature Genetics, 2007. 39(9): p. 1120-1126.
  3. Brems, H., et al., Glomus Tumors in Neurofibromatosis Type 1: Genetic, Functional, and Clinical Evidence of a Novel Association. Cancer Research, 2009. 69(18): p. 7393-7401.
  4. Cambiaghi, S., L. Restano, and R. Caputo, Juvenile Xanthogranuloma Associated with Neurofibromatosis 1: 14 Patients without Evidence of Hematologic Malignancies. Pediatric Dermatology, 2004. 21(2): p. 97-101.
  5. Cawthon, R.M., et al., A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell, 1990. 62(1): p. 193-201.
  6. Chabernaud, C., et al., Thalamo-Striatal T2-Weighted Hyperintensities (Unidentified Bright Objects) Correlate With Cognitive Impairments in Neurofibromatosis Type 1 During Childhood. Developmental Neuropsychology, 2009. 34(6): p. 736-748.
  7. Charles, S.J., Lisch Nodules in Neurofibromatosis Type 2. Archives of Ophthalmology, 1989. 107(11): p. 1571.
  8. Cnossen, M.H., et al., Endocrinologic Disorders and Optic Pathway Gliomas in Children With Neurofibromatosis Type 1. PEDIATRICS, 1997. 100(4): p. 667-670.
  9. Duffner, P.K., et al., The significance of MRI abnormalities in children with neurofibromatosis. Neurology, 1989. 39(3): p. 373-373.
  10. Eichenfield, L.F., et al., Guidelines of care for neurofibromatosis type 1. Journal of the American Academy of Dermatology, 1997. 37(4): p. 625-630.
  11. Evans, D.G.R., Neurofibromatosis type 2. Journal of Medical Genetics, 2000. 37(12): p. 897-904.
  12. Evans, D.G.R., et al., Management of the patient and family with neurofibromatosis 2: a consensus conference statement. British Journal of Neurosurgery, 2005. 19(1): p. 5-12.
  13. Ferner, R.E., 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. Annals of Oncology, 2008. 19(2): p. 390-394.
  14. Ferner, R.E., et al., Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. Journal of Medical Genetics, 2006. 44(2): p. 81-88.
  15. Ferrari, F., et al., Juvenile Xanthogranuloma and Nevus Anemicus in the Diagnosis of Neurofibromatosis Type 1. JAMA Dermatol, 2014. 150(1): p. 42.
  16. Fountain, J., et al., Physical mapping of a translocation breakpoint in neurofibromatosis. Science, 1989. 244(4908): p. 1085-1087.
  17. Gutmann, D.H., The Diagnostic Evaluation and Multidisciplinary Management of Neurofibromatosis 1 and Neurofibromatosis 2. JAMA, 1997. 278(1): p. 51.
  18. Gutmann, D.H. and F.S. Collins, The neurofibromatosis type 1 gene and its protein product, neurofibromin. Neuron, 1993. 10(3): p. 335-343.
  19. Habiby, R., et al., Precocious puberty in children with neurofibromatosis type 1. The Journal of Pediatrics, 1995. 126(3): p. 364-367.
  20. Huson, S.M., et al., A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. Journal of Medical Genetics, 1989. 26(11): p. 704-711.
  21. Hyman, S.L., A. Shores, and K.N. North, The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology, 2005. 65(7): p. 1037-1044.
  22. Jimbow, K., G. Szabo, and T.B. Fitzpatrick, Ultrastructure of Giant Pigment Granules (Macromelanosomes) in the Cutaneous Pigmented Macules of Neurofibromatosis. Journal of Investigative Dermatology, 1973. 61(5): p. 300-309.
  23. Johnson, B.L., Café au lait Spot in Neurofibromatosis and in Normal Individuals. Arch Dermatol, 1970. 102(4): p. 442.
  24. Kluwe, L., et al., Screening 500 unselected neurofibromatosis 1 patients for deletions of theNF1 gene. Human Mutation, 2004. 23(2): p. 111-116.
  25. Kraut, M.A., et al., Longitudinal evolution of unidentified bright objects in children with neurofibromatosis-1. American Journal of Medical Genetics, 2004. 129A(2): p. 113-119.
  26. Lee, W.S., et al., Partial Unilateral Lentiginosis Associated with Segmental Neurofibromatosis. The Journal of Dermatology, 1995. 22(12): p. 958-959.
  27. Leverkus, M., et al., Multiple unilateral schwannomas: segmental neurofibromatosis type 2 or schwannomatosis? Br J Dermatol, 2003. 148(4): p. 804-809.
  28. Levine, S.M., et al., Electrosurgical excision technique for the treatment of multiple cutaneous lesions in neurofibromatosis type I. Journal of Plastic, Reconstructive & Aesthetic Surgery, 2008. 61(8): p. 958-962.
  29. Lewis, R.A., et al., von Recklinghausen Neurofibromatosis. Ophthalmology, 1984. 91(8): p. 929-935.
  30. Lewis, R.A. and V.M. Riccardi, von Recklinghausen Neurofibromatosis. Ophthalmology, 1981. 88(4): p. 348-354.
  31. Listernick, R. and J. Charrow, Knowledge without truth: Screening for complications of neurofibromatosis type 1 in childhood. American Journal of Medical Genetics, 2004. 127A(3): p. 221-223.
  32. Listernick, R., et al., Optic pathway gliomas in children with neurofibromatosis 1: consensus statement from the NF1 optic pathway glioma task force. American Journal of Ophthalmology, 1997. 124(2): p. 274.
  33. Listernick, R., A.J. Mancini, and J. Charrow, Segmental neurofibromatosis in childhood. American Journal of Medical Genetics, 2003. 121A(2): p. 132-135.
  34. Mautner, V.F., Skin Abnormalities in Neurofibromatosis 2. Arch Dermatol, 1997. 133(12): p. 1539.
  35. Mautner, V.F., et al., Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1. Neuro-Oncology, 2008. 10(4): p. 593-598.
  36. Mautner, V.F., et al., Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions. Journal of Medical Genetics, 2010. 47(9): p. 623-630.
  37. McKusick, V.A., A Clinical, Pathological, and Genetic Study of Multiple Neurofibromatosis. Frank W. Crowe William J. Schull James V. Neel. The Quarterly Review of Biology, 1956. 31(4): p. 303-303.
  38. Messiaen, L., Clinical and Mutational Spectrum of Neurofibromatosis Type 1–like Syndrome. JAMA, 2009. 302(19): p. 2111.
  39. Mulvihill, J.J., Neurofibromatosis 1 (Recklinghausen Disease) and Neurofibromatosis 2 (Bilateral Acoustic Neurofibromatosis). Annals of Internal Medicine, 1990. 113(1): p. 39.
  40. Nunley, K.S., et al., Predictive Value of Café au Lait Macules at Initial Consultation in the Diagnosis of Neurofibromatosis Type 1. Arch Dermatol, 2009. 145(8).
  41. Pasmant, E., et al., NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype. Human Mutation, 2010. 31(6): p. E1506-E1518.
  42. Plum, F., Neurofibromatosis: Phenotype, natural history, and pathogenesis.By Vincent M. Riccardi and June E. Eichner Baltimore, Hopkins, 1986 305 pp, illustrated, $48.50. Annals of Neurology, 1987. 22(4): p. 561-561.
  43. Ragge, N.K. and F.L. Munier, Ancient neurofibromatosis. Nature, 1994. 368(6474): p. 815-815.
  44. Raygada, M., et al., Juvenile xanthogranuloma in a child with previously unsuspected neurofibromatosis type 1 and juvenile myelomonocytic leukemia. Pediatr. Blood Cancer, 2010. 54(1): p. 173-175.
  45. Reed, N. and D.H. Gutmann, Tumorigenesis in neurofibromatosis: new insights and potential therapies. Trends in Molecular Medicine, 2001. 7(4): p. 157-162.
  46. Riccardi, V.M., Pathophysiology of neurofibromatosis. Journal of the American Academy of Dermatology, 1980. 3(2): p. 157-166.
  47. Riccardi, V.M., von Recklinghausen Disease: 130 Years, in Neurofibromatosis Type 1. 2012, Springer Science + Business Media. p. 1-16.
  48. Sainz, J., et al., Mutations of the neurofibromatosis type 2 gene and lack of the gene product in vestibular schwannomas. Hum Mol Genet, 1994. 3(6): p. 885-891.
  49. Shen, M.H., P.S. Harper, and M. Upadhyaya, Molecular genetics of neurofibromatosis type 1 (NF1). Journal of Medical Genetics, 1996. 33(1): p. 2-17.
  50. Sørensen, S.A., J.J. Mulvihill, and A. Nielsen, Long-Term Follow-up of von Recklinghausen Neurofibromatosis. New England Journal of Medicine, 1986. 314(16): p. 1010-1015.
  51. Viskochil, D., et al., Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell, 1990. 62(1): p. 187-192.
  52. Wallace, M., et al., Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science, 1990. 249(4965): p. 181-186.
  53. Warbey, V.S., et al., [18F]FDG PET/CT in the diagnosis of malignant peripheral nerve sheath tumours in neurofibromatosis type-1. European Journal of Nuclear Medicine and Molecular Imaging, 2009. 36(5): p. 751-757.
  54. Williams, V.C., et al., Neurofibromatosis Type 1 Revisited. PEDIATRICS, 2009. 123(1): p. 124-133.
  55. Zanca, A. and A. Zanca, Antique Illustrations of Neurofibromatosis. International Journal of Dermatology, 1980. 19(1): p. 55-58.
  56. Zvulunov, A., Juvenile Xanthogranuloma, Neurofibromatosis, and Juvenile Chronic Myelogenous Leukemia. Arch Dermatol, 1995. 131(8): p. 904.
  57. Zvulunov, A., Juvenile Xanthogranuloma, Neurofibromatosis, and Juvenile Chronic Myelogenous Leukemia. Arch Dermatol, 1996. 132(6): p. 712.