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Neurofibromatosis

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The Growing Spine

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Abstract

Neurofibromatosis type 1 (NF-1) is the most common human single-gene disorder. Skeletal complications usually present early in life and can be attributed to abnormalities of bone growth, remodeling, and repair in NF-1 or can be secondary to nearby soft-tissue abnormalities associated with NF-1. Scoliosis is the most common osseous manifestation of NF-1. The management of spinal disorders in young children in NF-1 continues to be problematic. It is important to recognize the dystrophic curve and to distinguish it from the non-dystrophic curve. The treatment of non-dystrophic curvatures is very similar to idiopathic scoliosis. The current state-of-the-art treatment for significant deformity or progressive deformities in the patient achieving skeletal maturity is combined anterior and posterior spinal arthrodesis. The use of growing rods allows more longitudinal growth than fusion and more life freedom than bracing. However, the multiple surgeries increase the potential for complications including infections. The intent of this chapter is to present the spinal deformities that are most commonly associated with NF-1 and to identify the current management of spinal disorders based on the most recent literature.

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References

  1. Virchow R (1847) Ueber die reform der pathologischen und therpeutischen anschaungen durch die mikrokopischen untersuchungen. Arch Pathol Anat Physiol Klin Med 1:207–255

    Article  Google Scholar 

  2. Von Recklinghausen FD (1882) Ueber die multiplen fibrome der haut und ihre besiehung zu den multiplen neuromen. Hirschwald, Berlin

    Google Scholar 

  3. Rieley MB, Stevenson DA, Viskochil DH, Tinkle BT, Martin LJ, Schorry EK (2011) Variable expression of neurofibromatosis 1 in monozygotic twins. Am J Med Genet A 155A:478–485

    Article  PubMed  Google Scholar 

  4. Easton DF, Ponder MA, Huson SM, Ponder BA (1993) An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes. Am J Hum Genet 53:305–313

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Elefteriou F, Kolanczyk M, Schindeler A, Viskochil DH, Hock JM, Schorry EK et al (2009) Skeletal abnormalities in neurofibromatosis type 1: approaches to therapeutic options. Am J Med Genet A 149A:2327–2338

    Article  CAS  PubMed  Google Scholar 

  6. Dulai S, Briody J, Schindeler A, North KN, Cowell CT, Little DG (2007) Decreased bone mineral density in neurofibromatosis type 1: results from a pediatric cohort. J Pediatr Orthop 27:472–475

    Article  PubMed  Google Scholar 

  7. Lammert M, Kappler M, Mautner VF, Lammert K, Störkel S, Friedman JM et al (2005) Decreased bone mineral density in patients with neurofibromatosis 1. Osteoporos Int 16:1161–1166

    Article  PubMed  Google Scholar 

  8. Stevenson DA, Moyer-Mileur LJ, Murray M, Slater H, Sheng X, Carey JC, Dube B et al (2007) Bone mineral density in children and adolescents with neurofibromatosis type 1. J Pediatr 150:83–88

    Article  PubMed Central  PubMed  Google Scholar 

  9. Duman O, Ozdem S, Turkkahraman D, Olgac ND, Gungor F, Haspolat S (2008) Bone metabolism markers and bone mineral density in children with neurofibromatosis type-1. Brain Dev 30:584–588

    Article  PubMed  Google Scholar 

  10. Halmai V, Domán I, de Jonge T, Illés T (2002) Surgical treatment of spinal deformities associated with neurofibromatosis type 1. Report of 12 cases. J Neurosurg 97(3 Suppl):310–316

    PubMed  Google Scholar 

  11. Akbarnia BA, Gabriel KR, Beckman E, Chalk D (1992) Prevalence of scoliosis in neurofibromatosis. Spine (Phila Pa 1976) 17(8 Suppl):S244–S248

    Article  CAS  Google Scholar 

  12. Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG (2007) Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet 44:81–88

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Goldberg NS, Collins FS (1991) The hunt for the neurofibromatosis gene. Arch Dermatol 127:1705–1707

    Article  CAS  PubMed  Google Scholar 

  14. Collins FS, Ponder BA, Seizinger BR, Epstein CJ (1989) The von Recklinghausen neurofibromatosis region on chromosome 17--genetic and physical maps come into focus. Am J Hum Genet 44:1–5

    PubMed Central  CAS  PubMed  Google Scholar 

  15. Legius E, Marchuk DA, Collins FS, Glover TW (1993) Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis. Nat Genet 3:122–126

    Article  CAS  PubMed  Google Scholar 

  16. Vitale MG, Guha A, Skaggs DL (2002) Orthopaedic manifestations of neurofibromatosis in children: an update. Clin Orthop Relat Res 401:107–118

    Article  PubMed  Google Scholar 

  17. Cawthon RM, Weiss R, Xu GF, Viskochil D, Culver M, Stevens J et al (1990) A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell 62:193–201

    Article  CAS  PubMed  Google Scholar 

  18. Sponseller P (2003) The spine in skeletal syndromes and dysplasias. In: DeWald RL (ed) Spinal deformities. The comprehensive text. Thieme, New York, pp 701–717

    Google Scholar 

  19. North K (1993) Neurofibromatosis type 1: review of the first 200 patients in an Australian clinic. J Child Neurol 8:395–402

    Article  CAS  PubMed  Google Scholar 

  20. National Institutes of Health Consensus Development Conference (1988) Neurofibromatosis. Conference Statement. Arch Neurol 45:575–578

    Google Scholar 

  21. DeBella K, Szudek J, Friedman JM (2000) Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics 105(3 Pt 1):608–614

    Article  CAS  PubMed  Google Scholar 

  22. Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL (2009) Neurofibromatosis type 1 revisited. Pediatrics 123:124–133

    Article  PubMed  Google Scholar 

  23. Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson SM et al (2010) Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A 152A(2):327–332

    Article  CAS  PubMed  Google Scholar 

  24. Evans DG (2009) Neurofibromatosis type 2 (NF2): a clinical and molecular review. Orphanet J Rare Dis 4:16

    Article  PubMed Central  PubMed  Google Scholar 

  25. Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R et al (2007) Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nat Genet 39:1120–1126

    Article  CAS  PubMed  Google Scholar 

  26. Winter RB, Lonstein JE, Anderson M (1988) Neurofibromatosis hyperkyphosis: a review of 33 patients with kyphosis of 80 degrees or greater. J Spine Disord 1:39–49

    CAS  Google Scholar 

  27. Schorry EK, Crawford AH, Egelhoff JC, Lovell AM, Saal HM (1997) Thoracic tumors in children with neurofibromatosis-1. Am J Med Genet 74:533–537

    Article  CAS  PubMed  Google Scholar 

  28. Durrani AA, Crawford AH, Chouhdry SN, Saifuddin A, Morley TR (2000) Modulation of spinal deformities in patients with neurofibromatosis type 1. Spine (Phila Pa 1976) 25:69–75

    Article  CAS  Google Scholar 

  29. Shufflebarger HL (1989) Cotrel–Dubousset instrumentation in neurofibromatosis spinal problems. Clin Orthop Relat Res 245:24–28

    PubMed  Google Scholar 

  30. Holt JF, Wright EM (1948) The radiologic features of neurofibromatosis. Radiology 51:647–664

    Article  CAS  PubMed  Google Scholar 

  31. Lykissas MG, Schorry EK, Crawford AH, Gaines S, Rieley M, Jain VV (2013) Does the presence of dystrophic features in patients with type 1 neurofibromatosis and spinal deformities increase the risk of surgery? Spine (Phila Pa 1976) 38:1595–1601

    Article  Google Scholar 

  32. Crawford AH (2001) Neurofibromatosis. In: Weinstein SL (ed) The pediatric spine: principles and practice, 2nd edn. Lippincott Williams & Wilkins, Philadelphia, pp 471–490

    Google Scholar 

  33. Chaglassian JH, Riseborough EJ, Hall JE (1976) Neurofibromatous scoliosis. J Bone Joint Surg Am 58:695–702

    CAS  PubMed  Google Scholar 

  34. Funasaki H, Winter RB, Lonstein JB, Denis F (1994) Pathophysiology of spinal deformities in neurofibromatosis. J Bone Joint Surg Am 76:692–700

    CAS  PubMed  Google Scholar 

  35. Kim HW, Weinstein SL (1997) Spine update: the management of scoliosis in neurofibromatosis. Spine (Phila Pa 1976) 22:2770–2776

    Article  CAS  Google Scholar 

  36. Kissil JL, Blakeley JO, Ferner RE, Huson SM, Kalamarides M, Mautner VF et al (2010) What’s new in neurofibromatosis? Proceedings from the 2009 NF Conference: new frontiers. Am J Med Genet A 152A:269–283

    Article  PubMed Central  PubMed  Google Scholar 

  37. Casselman ES, Mandell GA (1979) Vertebral scalloping in neurofibromatosis. Radiology 131:89–94

    Article  CAS  PubMed  Google Scholar 

  38. Laws JW, Pallis C (1963) Spinal deformities in neurofibromatosis. J Bone Joint Surg Br 45:674–682

    CAS  PubMed  Google Scholar 

  39. Salerno NR, Edeiken J (1970) Vertebral scalloping in neurofibromatosis. Radiology 97:509–510

    Article  CAS  PubMed  Google Scholar 

  40. Heard G, Payne EE (1962) Scalloping of the vertebral bodies in von Recklinghausen’s disease of the nervous system (neurofibromatosis). J Neurol Neurosurg Psychiatry 25:345–351

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Hunt JC, Pugh DG (1961) Skeletal lesions in neurofibromatosis. Radiology 76:1–20

    Article  CAS  PubMed  Google Scholar 

  42. Crawford AH, Bagamery N (1986) Osseous manifestations of neurofibromatosis in childhood. J Pediatr Orthop 6:72–88

    Article  PubMed  Google Scholar 

  43. Tsirikos AI, Ramachandran M, Lee J, Saifuddin A (2004) Assessment of vertebral scalloping in neurofibromatosis type 1 with plain radiography and MRI. Clin Radiol 59:1009–1017

    Article  CAS  PubMed  Google Scholar 

  44. Stevenson DA, Zhou H, Ashrafi S, Messiaen LM, Carey JC, D’Astous JL et al (2006) Double inactivation of NF1 in tibial pseudarthrosis. Am J Hum Genet 79:143–148

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Zhang W, Rhodes SD, Zhao L, He Y, Zhang Y, Shen Y et al (2011) Primary osteopathy of vertebrae in a neurofibromatosis type 1 murine model. Bone 48:1378–1387

    Article  PubMed Central  PubMed  Google Scholar 

  46. Stone JW, Bridwell KH, Shackelford GD, Abramson CL (1987) Dural ectasia associated with spontaneous dislocation of the upper part of the thoracic spine in neurofibromatosis. A case report and review of the literature. J Bone Joint Surg Am 69:1079–1083

    CAS  PubMed  Google Scholar 

  47. Flood BM, Butt WP, Dickson RA (1986) Rib penetration of the intervertebral foraminae in neurofibromatosis. Spine (Phila Pa 1976) 11:172–174

    Article  CAS  Google Scholar 

  48. Major MR, Huizenga BA (1988) Spinal cord compression by displaced ribs in neurofibromatosis. A report of three cases. J Bone Joint Surg Am 70:1100–1102

    CAS  PubMed  Google Scholar 

  49. Crawford AH (1989) Pitfalls of spinal deformities associated with neurofibromatosis in children. Clin Orthop Relat Res 245:29–42

    PubMed  Google Scholar 

  50. Haddad FS, Williams RL, Bentley G (1995) The cervical spine in neurofibromatosis. Br J Hosp Med 53:318–319

    CAS  PubMed  Google Scholar 

  51. Ogilvie JW (1995) Moe’s textbook of scoliosis and other spinal deformities, 3rd edn. WB Saunders, Philadelphia

    Google Scholar 

  52. Yong-Hing K, Kalamchi A, MacEwen GD (1979) Cervical spine abnormalities in neurofibromatosis. J Bone Joint Surg Am 6:695–699

    Google Scholar 

  53. Curtis BH, Fisher RL, Butterfield WL, Saunders FP (1969) Neurofibromatosis with paraplegia. Report of eight cases. J Bone Joint Surg Am 51:843–861

    CAS  PubMed  Google Scholar 

  54. Isu T, Miyasaka K, Abe H, Iwasaki Y, Tsuru M, Kitaoka K et al (1983) Atlantoaxial dislocation associated with neurofibromatosis. Report of three cases. J Neurosurg 58:451–453

    Article  CAS  PubMed  Google Scholar 

  55. Crawford AH, Schorry EK (1999) Neurofibromatosis in children: the role of the orthopaedist. J Am Acad Orthop Surg 7:217–230

    CAS  PubMed  Google Scholar 

  56. Crawford AH, Lykissas MG, Schorry EK, Gaines S, Jain VV (2012) Neurofibromatosis: etiology, commonly encountered spinal deformities, common complications and pitfalls of surgical treatment. Spinal Deformity. Preview Issue:85–94

    Google Scholar 

  57. Holt JF, Wright EM (1948) The radiologic features of neurofibromatosis. Radiology 51:647–663

    Article  CAS  PubMed  Google Scholar 

  58. Winter RB, Lonstein JE, Anderson M (1988) Neurofibromatosis hyperkyphosis: a review of 33 patients with kyphosis of 80 degrees or greater. J Spinal Disord 1:39–49

    Article  CAS  PubMed  Google Scholar 

  59. Crawford AH, Schorry EK (2006) Neurofibromatosis update. J Pediatr Orthop 26:413–423

    Article  PubMed  Google Scholar 

  60. Holt RT, Johnson JR (1989) Cotrel–Dubousset instrumentation in neurofibromatosis spine curves. A preliminary report. Clin Orthop Relat Res 245:19–23

    PubMed  Google Scholar 

  61. Sirois JL 3rd, Drennan JC (1990) Dystrophic spinal deformity in neurofibromatosis. J Pediatr Orthop 10:522–526

    Article  PubMed  Google Scholar 

  62. Crawford AH, Parikh S, Schorry EK, Von Stein D (2007) The immature spine in type-1 neurofibromatosis. J Bone Joint Surg Am 89(Suppl 1):123–142

    Article  PubMed  Google Scholar 

  63. Calvert PT, Edgar MA, Webb PJ (1989) Scoliosis in neurofibromatosis. The natural history with and without operation. J Bone Joint Surg Br 71:246–251

    CAS  PubMed  Google Scholar 

  64. Wilde PH, Upadhyay SS, Leong JC (1994) Deterioration of operative correction in dystrophic spinal neurofibromatosis. Spine (Phila Pa 1976) 19:1264–1270

    Article  CAS  Google Scholar 

  65. Betz RR, Iorio R, Lombardi AV, Clancy M, Steel HH (1989) Scoliosis surgery in neurofibromatosis. Clin Orthop Relat Res 245:53–56

    PubMed  Google Scholar 

  66. Winter RB, Moe JH, Bradford DS, Lonstein JE, Pedras CV, Weber AH (1979) Spine deformity in neurofibromatosis. A review of one hundred and two patients. J Bone Joint Surg Am 61:677–694

    CAS  PubMed  Google Scholar 

  67. Mehlman CT, Al-Sayyad MJ, Crawford AH (2004) Effectiveness of spinal release and halo-femoral traction in the management of severe spinal deformity. J Pediatr Orthop 24:667–673

    Article  PubMed  Google Scholar 

  68. Rinella A, Lenke L, Whitaker C, Kim Y, Park SS, Peelle M et al (2005) Perioperative halo-gravity traction in the treatment of severe scoliosis and kyphosis. Spine (Phila Pa 1976) 30:475–482

    Article  Google Scholar 

  69. Lalueza MP, Colomina MJ, Bago J, Clemente S, Godet C (2005) Analysis of nutritional parameters in idiopathic scoliosis patients after major spinal surgery. Eur J Clin Nutr 59:720–722

    Article  CAS  PubMed  Google Scholar 

  70. Al-Sayyad MJ, Crawford AH, Wolf RK (2004) Early experiences with video-assisted thoracoscopic surgery: our first 70 cases. Spine (Phila Pa 1976) 29:1945–1951; Discussion 52

    Article  Google Scholar 

  71. Mulpuri K, LeBlanc JG, Reilly CW, Poskitt KJ, Choit RL, Sahajpal V et al (2005) Sternal split approach to the cervicothoracic junction in children. Spine (Phila Pa 1976) 30:E305–E310

    Article  Google Scholar 

  72. Parisini P, Di Silvestre M, Greggi T, Paderni S, Cervellati S, Savini R (1999) Surgical correction of dystrophic spinal curves in neurofibromatosis. A review of 56 patients. Spine (Phila Pa 1976) 24:2247–2253

    Article  CAS  Google Scholar 

  73. Singh K, Samartzis D, An HS (2005) Neurofibromatosis type I with severe dystrophic kyphoscoliosis and its operative management via a simultaneous anterior–posterior approach: a case report and review of the literature. Spine J 5:461–466

    Article  PubMed  Google Scholar 

  74. Lykissas MG, Crawford AH, Jain VV (2013) Complications of surgical treatment of pediatric spinal deformities. Orthop Clin North Am 44:357–370

    Article  PubMed  Google Scholar 

  75. Akbarnia BA, Marks DS, Boachie-Adjei O, Thompson AG, Asher MA (2005) Dual growing rod technique for the treatment of progressive early-onset scoliosis: a multicenter study. Spine (Phila Pa 1976) 30(17 Suppl):S46–S57

    Article  Google Scholar 

  76. Thompson GH, Akbarnia BA, Kostial P, Poe-Kochert C, Armstrong DG, Roh J et al (2005) Comparison of single and dual growing rod techniques followed through definitive surgery: a preliminary study. Spine (Phila Pa 1976) 30:2039–2044

    Article  Google Scholar 

  77. Nazzaro JM, Arbit E, Burt M (1994) “Trap door” exposure of the cervicothoracic junction. Technical note. J Neurosurg 80:338–341

    Article  CAS  PubMed  Google Scholar 

  78. Winter RB, Lovell WW, Moe JH (1975) Excessive thoracic lordosis and loss of pulmonary function in patients with idiopathic scoliosis. J Bone Joint Surg Am 57:972–977

    CAS  PubMed  Google Scholar 

  79. Hsu LC, Lee PC, Leong JC (1984) Dystrophic spinal deformities in neurofibromatosis. Treatment by anterior and posterior fusion. J Bone Joint Surg Br 66:495–499

    CAS  PubMed  Google Scholar 

  80. Hirschfeld SS, Rudner C, Nash CL Jr, Nussbaum E, Brower EM (1982) Incidence of mitral valve prolapse in adolescent scoliosis and thoracic hypokyphosis. Pediatrics 70:451–454

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnatti, OH, 45229, USA

    Viral V. Jain MD

  2. Department of Orthopaedics, University of Ioannina School of Medicine, Ioannina, Greece

    Marios G. Lykissas MD, PhD

  3. Department of Orthopaedics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Alvin H. Crawford MD, FACS

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  1. Viral V. Jain MD
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  2. Marios G. Lykissas MD, PhD
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  3. Alvin H. Crawford MD, FACS
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Correspondence to Viral V. Jain MD .

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Editors and Affiliations

  1. San Diego Center for Spinal Disorders Medical Group, Inc., La Jolla, California, USA

    Behrooz A. Akbarnia

  2. Hacettepe University Dept. Orthopedics & Traumatology, Sihhiye, Ankara, Turkey

    Muharrem Yazici

  3. Rainbow Babies & Children's Hospital, Cleveland, Ohio, USA

    George H. Thompson

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Jain, V.V., Lykissas, M.G., Crawford, A.H. (2016). Neurofibromatosis. In: Akbarnia, B., Yazici, M., Thompson, G. (eds) The Growing Spine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-48284-1_16

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