Orthopaedic manifestations of neurofibromatosis type 1: A case report

Năstase,Florentina; Radaschin,Diana Sabina; Niculeț,Elena; Brădeanu,Andrei Vlad; Verenca,Mădălina Codruța; Nechita,Aurel; Chioncel,Valentin; Nwabudike,Lawrence Chukwudi; Baroiu,Liliana; Polea,Eduard Drima; Fotea,Silvia; Anghel,Lucretia; Nechifor,Alexandru; Tatu,Alin Laurenţiu

doi:10.3892/etm.2021.11058

Orthopaedic manifestations of neurofibromatosis type 1: A case report

Authors:
- Florentina Năstase
- Diana Sabina Radaschin
- Elena Niculeț
- Andrei Vlad Brădeanu
- Mădălina Codruța Verenca
- Aurel Nechita
- Valentin Chioncel
- Lawrence Chukwudi Nwabudike
- Liliana Baroiu
- Eduard Drima Polea
- Silvia Fotea
- Lucretia Anghel
- Alexandru Nechifor
- Alin Laurenţiu Tatu
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Affiliations: Department of Neuropsychomotor Rehabilitation, ‘Sf. Ioan’ Clinical Hospital for Children, 800487 Galati, Romania, Clinical Medical Department, Faculty of Medicine and Pharmacy, ‘Dunarea de Jos’ University, 800010 Galati, Romania, Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, ‘Dunarea de Jos’ University, 800010 Galati, Romania, Department of Neuropsychomotor Rehabilitation, ‘Sf. Ioan’ Clinical Hospital for Children, 800487 Galați, Romania, Department of Pediatrics, ‘Sf. Ioan’ Clinical Hospital for Children, 800487 Galati, Romania, Cardio‑thoracic Department, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania, Department of Diabetic Foot Care, ‘N. Paulescu’ National Institute of Diabetes, 011233 Bucharest, Romania, Medical Clinical Department, Faculty of Medicine and Pharmacy, ‘Dunarea de Jos’ University, 800010 Galati, Romania
Published online on: December 13, 2021 https://doi.org/10.3892/etm.2021.11058
Article Number: 135
Copyright: © Năstase et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neurofibromatosis type 1 (NF1) or von Recklinghausen disease is one of the most common autosomal dominant genetic diseases. It is characterized by ‘café‑au‑lait’ spots and multiple tumors starting from the central and peripheric nervous system. The diagnosis is determined on two out of seven criteria: i) A total of 6 or more light brown spots larger than 5 mm in diameter (pre‑puberty) or 15 mm in diameter (post‑puberty); ii) a total of 2 or more neurofibromas or one plexiform neurofibroma; iii) axillary or inguinal freckling; iv) optic glioma; v) a total of 2 or more Lisch nodules; vi) bone abnormalities: tibia pseudarthrosis or dysplasia of the sphenoid wing; and vii) a relative of first degree having an NF1 diagnosis. A total of ~50% of patients have significant musculoskeletal manifestation, with scoliosis and congenital pseudarthrosis of tibia most common. Management of the orthopaedic manifestations of NF1 is often difficult. Due to NF1 influencing multiple organ systems, patients are likely to benefit most from a multidisciplinary treatment strategy.

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1	Sehgal NV, Verma P and Chatterjee K: Type 1 neurofibromatosis (von Recklinghausen disease). Cutis. 96:e23–26. 2015.PubMed/NCBI
2	Leroy K, Dumas V, Martin-Garcia N, Falzone MC, Voisin MC, Wechsler J, Revuz J, Creange A, Levy E, Lantieri L, et al: Malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1: A clinicopathologic and molecular study of 17 patients. Arch Dermatol. 137:908–913. 2001.PubMed/NCBI
3	Feldman DS, Jordan C and Fonseca L: Orthopaedic manifestations of neurofibromatosis type 1. J Am Acad Orthop Surg. 18:346–357. 2010.PubMed/NCBI View Article : Google Scholar
4	Hirbe AC and Gutman DH: Neurofibromatosis type 1: A multidisciplinary approach to care. Lancet Neurol. 13:834–843. 2014.PubMed/NCBI View Article : Google Scholar
5	Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, Upadhyaya M, Towers R, Gleeson M, Steiger C and Kirby A: Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 44:81–88. 2007.PubMed/NCBI View Article : Google Scholar
6	Boyd KP, Korf BR and Theos A: Neurofibromatosis type 1. J Am Acad Dermatol. 61:1–14. 2009.PubMed/NCBI View Article : Google Scholar
7	Guler M, Aydin T and Poyraz E: Neurofibromatosis type 1 with invasive spinal cord compression (case report). Afr J Pharm Pharmacol. 7:1615–1618. 2013.
8	Friedman JM: Epidemiology of neurofibromatosis type 1. Am J Med Genet. 89:1–6. 1999.PubMed/NCBI
9	Lammert M, Friedman JM, Kluwe VF and Mautner VF: Prevalence of neurofibromatosis 1 in German children at elementary school enrollment. Arch Dermatol. 141:71–74. 2005.PubMed/NCBI View Article : Google Scholar
10	Huson SM, Compston DA, Clark P and Harper PS: A genetic study of von Recklinghausen neurofibromatosis in south east Wales. Prevalence, fitness, mutaton rate and effect of parental transmision on severity. J Med Genet. 26:704–711. 1989.PubMed/NCBI View Article : Google Scholar
11	Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL and Johnson KJ: Neurofibromatosis type 1. Nat Rev Dis Primers. 3(17004)2017.PubMed/NCBI View Article : Google Scholar
12	Nica SC, Mihailescu G, Nica SM, Baetu C, Clatici VG and Buruga I: Neurofibromatosis-one disease for a multidisciplinary team. RoJCED. 3:38–49. 2016.
13	Viskochil D, Buchberg AM, Xu G, Cawthon RM, Stevens J, Wolff RK, Culver M, Carey JC, Copeland NG and Jenkins NA: Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell. 62:187–192. 1990.PubMed/NCBI View Article : Google Scholar
14	Li Y, O'Connell P, Breidenbach HH, Cawthon R, Stevens J, Xu G, Neil S, Robertson M, White R and Viskochil D: Genomic organization of the neurofibromatosis 1 gene (Nf1). Genomics. 25:9–18. 1995.PubMed/NCBI View Article : Google Scholar
15	Daston MM, Scrable H, Nordlund M, Sturbaum AK, Nissen LM and Ratner N: The protein product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells and oligodendrocytes. Neuron. 8:415–428. 1992.PubMed/NCBI View Article : Google Scholar
16	Gutmann DH, Parada LF, Silva AJ and Ratner N: Neurofibromatosis type 1: Modeling CNS dysfunction. J Neurosci. 32:14087–14093. 2012.PubMed/NCBI View Article : Google Scholar
17	Peltonen S: Neurofibromatosis type 1: Dermatologists should take an active role. Forum for Nord Derm Ven. 13:74–77. 2008.
18	Antônio JR, Goloni-Bertollo EM and Trídico LA: Neurofibromatosis: Chronological history and current issues. An Bras Dermatol. 88:329–343. 2013.PubMed/NCBI View Article : Google Scholar
19	Stocker KM, Baizer L, Coston T, Sherman L and Ciment G: Regulated expression of neurofibromin in migrating neural crest cells of avian embryos. J Neurobiol. 27:535–552. 1995.PubMed/NCBI View Article : Google Scholar
20	National Institutes of Health Consensus Development Conference Statement: Neurofibromatosis. Bethesda, Md., USA July 13-15, 1987. Neurofibromatosis. 1:172–178. 1988.PubMed/NCBI
21	Tonsgard JH: Clinical manifestations and management of neurofibromatosis type 1. Semin Pediatr Neurol. 13:2–7. 2006.PubMed/NCBI View Article : Google Scholar
22	Ferner RE: Neurofibromatosis 1. Eur J Hum Genet. 15:131–138. 2007.PubMed/NCBI View Article : Google Scholar
23	Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B and Maria BL: Neurofibromatosis type 1 revisited. Pediatrics. 123:124–133. 2009.PubMed/NCBI View Article : Google Scholar
24	Kolanczyk M, Mautner V, Kossler N, Nguyen R, Kuhnisch J, Zemojtel T, Jamsheer A, Wegener E, Thurisch B, Tinschert S, et al: MIA is a potential biomarker for tumour load in neurofibromatosis type 1. BMC Med. 9(82)2011.PubMed/NCBI View Article : Google Scholar
25	Tatu AL: Umbilicated blue black lesion on the lateral thorax. J Cutan Med Surg. 21(252)2017.PubMed/NCBI View Article : Google Scholar
26	Valeyrie-Allanore L, Ortonne N, Lentieri L, Ferkal S, Wechsler J, Bagot M and Wolkenstein P: Histopathologically dysplastic neurofibromas in neurofibromatosis 1: Diagnostic criteria, prevalence and clinical signifiance. Br J Dermatol. 158:1008–1012. 2008.PubMed/NCBI View Article : Google Scholar
27	Montani D, Coulet F, Girerd B, Eyries M, Bergot E, Mal H, Biondi G, Dromer C, Hugues T, Marquette C, et al: Pulmonary hypertension in patients with neurofibromatosis type I. Medicine (Baltimore). 90:201–211. 2011.PubMed/NCBI View Article : Google Scholar
28	Wang J, Wei G, Wang Z and Huang H: Detection of severe hypertension in a patient with neurofibromatosis type 1 during anesthesia induction: A case report. J Med Case Rep. 13(349)2019.PubMed/NCBI View Article : Google Scholar
29	Nanda A: Autoimmune diseases associated with neurofibromatosis type 1. Pediatr Dermatol. 25:392–393. 2008.PubMed/NCBI View Article : Google Scholar
30	Tatu AL and Ionescu MA: Multiple autoimmune syndrome type III-thyroiditis, vitiligo and alopecia areata. Acta Endocrinol (Buchar). 13:124–125. 2017.PubMed/NCBI View Article : Google Scholar
31	Tandon S, Singh A, Arora P and Gautam RK: Neurofibromatosis with vitiligo: An uncommon association rather than coexistence? An Bras Dermatol. 94:624–626. 2019.PubMed/NCBI View Article : Google Scholar
32	Miraglia E, Calvieri S and Giustini S: Neurofibromatosis type 1 and lichen sclerosus: An uncommon association. G Ital Dermatol Venereol. 152:83–84. 2017.PubMed/NCBI View Article : Google Scholar
33	Mihăilă B, Dinică RM, Tatu AL and Buzia OD: New insights in vitiligo treatments using bioactive compounds from Piper nigrum. Exp Ther Med. 17:1039–1044. 2019.PubMed/NCBI View Article : Google Scholar
34	Tatu AL and Nwabudike LC: The treatment options of male genital lichen sclerosus et atrophicus: Treatments of genital lichen sclerosus. In: Proceedings of the 14th National Congress of Urogynecology and the National Conference of the Romanian Association for the Study of Pain, pp262-264, 2017.
35	Korf BR: Diagnostic outcome in children with cafe au lait spots. Pediatrics. 90:924–927. 1992.PubMed/NCBI
36	Stevenson DA, Moyer-Mileur LJ, Murray M, Slater H, Sheng X, Carey JC, Dube B and Viskochil DH: Bone mineral density in children and adolescents with neurofibromatosis type 1. J Pediatr. 150:83–88. 2007.PubMed/NCBI View Article : Google Scholar
37	Friedman JM and Birch PH: Type I neurofibromatosis: A descriptive analysis of the disorder in 1728 patients. Am J Med Genet. 70:138–143. 1997.
38	Gilbert A and Brockman R: Congenital pseudarthrosis of the tibia: Long-term followup of 29 cases treated by microvascularbone transfer. Clin Orthop Relat Res. 314:37–44. 1995.PubMed/NCBI
39	Sulaiman AR, Nordin S, Faisham WI, Zulmi W and Halim AS: Residual nonunion following vascularized fibular graft treatment for congenital pseudarthosis of the tibia: A report of two cases. J Orthop Surg (Hong Kong). 14:64–66. 2006.PubMed/NCBI View Article : Google Scholar
40	Stevenson DA, Birch PH, Friedman JM, Viskochil DH, Balestrazzi P, Boni S, Buske A, Korf BR, Niimura M, Pivnick EK, et al: Descriptive analysis of tibial pseudarthrosis in patients with neurofibromatosis 1. Am J Med Genet. 84:413–419. 1999.PubMed/NCBI View Article : Google Scholar
41	Kong LD, Cheng HX and Nie T: Treat the congenital pseudarthrosis of the tibia with Ilizarov technology. Case report. Medicine (Baltimore). 97(e13384)2018.PubMed/NCBI View Article : Google Scholar
42	Sakamoto A, Yoshida T, Yamamoto H, Oda Y, Tsuneyoshi M and Iwamoto Y: Congenital pseudarthrosis of the tibia: Analysis of the histology and the NF1 gene. J Orthop Sci. 12:361–365. 2007.PubMed/NCBI View Article : Google Scholar
43	Tuncay IC, Johnston CE II and Birch JG: Spontaneous resolution of congenital anterolateral bowing of the tibia. J Pediatr Orthop. 14:599–602. 1994.PubMed/NCBI View Article : Google Scholar
44	Crawford AH and Schorry EK: Neurofibromatosis in children: The role of the orthopaedist. J Am Acad Orthop Surg. 7:217–230. 1999.PubMed/NCBI View Article : Google Scholar
45	Traub JA, O'Connor W and Masso PD: Congenital pseudarthrosis of the tibia: A retrospective review. J Pediatr Orthop. 19:735–738. 1999.PubMed/NCBI
46	Karol LA, Haideri NF, Halliday SE, Smitherman TB and Johnston CE II: Gait analysis and muscle strength in children with congenital pseudarthrosis of the tibia: The effect of treatment. J Pediatr Orthop. 18:381–386. 1998.PubMed/NCBI
47	Vanderstappen J, Lammens J, Berger P and Laumen A: Ilizarov bone transplant as a treatment of congenital pseudarthrosis of the tibia: A long-term follow-up study. J Child Orthop. 9:319–324. 2015.PubMed/NCBI View Article : Google Scholar
48	Ippolito E, Corsi A, Grill F, Wientroub S and Bianco P: Pathology of bone lesions associated with congenital pseudarthrosis of the leg. J Pediatr Orthop B. 9:3–10. 2000.PubMed/NCBI View Article : Google Scholar
49	Hefti F, Bollini C, Dungl P, Fixsen J, Grill F, Ippolito E, Romanus B, Tudisco C and Wientroub S: Congenital pseudarthrosis of the tibia: History, etiology, classification and epideiologic data. J Pediatr Orthop B. 9:11–15. 2000.PubMed/NCBI View Article : Google Scholar
50	Lehman WB, Atar D, Feldman DS, Gordon JC and Grant AD: Congenital pseudarthrosis of the tibia. J Pediatr Orthop B. 9:103–107. 2000.PubMed/NCBI View Article : Google Scholar
51	Tudisco C, Bollini C, Dungel P, Fixen J, Grill F, Hefti F, Romanus B and Wientroub S: Functional results at the end of skeletal growth in 30 patients affected by congenital pseudarthrosis of the tibia. J Pediatr Orthop B. 9:94–102. 2000.PubMed/NCBI View Article : Google Scholar
52	Grill F, Bollini C, Dungl P, Fixsen J, Hefti F, Ippolito E, Romanus B, Tudisco C and Wientroub S: Treatment approaches for congenital psedarthrosis of tibia: Results of the EPOS multicenter study. European Paediatric Orthopaedic Society (EPOS). J Pediatr Orthop B. 9:75–89. 2000.PubMed/NCBI View Article : Google Scholar
53	Elefteriou F, Kolnczyk M, Schindeler A, Viskochil DH, Hock JM, Schorry EK, Crawford AH, Friedman JM, Little D, Peltonen J, et al: Skeletal abnormalities in neurofibromatosis type 1: Approaches to therapeutic options. Am J Med Genet A. 149A. 2327–2338. 2009.PubMed/NCBI View Article : Google Scholar
54	Dobbs MB, Rich MM, Gordon JE, Szymanski DA and Schoenecker PL: Use of an intramedullary rod for treatment of congenital pseudarthrosis of the tibia: A long-term follow-up study. J Bone Joint Surg Am. 86:1186–1197. 2004.PubMed/NCBI View Article : Google Scholar
55	Boero S, Catagni M, Donzelli O, Facchini R and Frediani PV: Congenital pseudarthrosis of the tibia associated with neurofibromatosis 1: Treatment with Ilizarov's device. J Pediatr Orthop. 17:675–684. 1997.PubMed/NCBI View Article : Google Scholar
56	Velan CJ, Katz K and Hendel D: Failed treatment of congenital pseudarthrosis of the tibia-a case of Ilizarov transportation of proximal tibia with artrodesis to talus. Acta Orthop Scand. 69:433–434. 1998.PubMed/NCBI View Article : Google Scholar
57	Ramachandran M, Tsirikos AI, Lee J and Saifuddin A: Whole-spine magnetic resonance imaging in patients with neurofibromatosis type 1 and spinal deformity. J Spinal Disord Tech. 17:483–491. 2004.PubMed/NCBI View Article : Google Scholar
58	Singh K, Samartzis D and An HS: Neurofibromatosis type 1 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. 2005.PubMed/NCBI View Article : Google Scholar
59	Li M, Fang X, Li Y, Ni J, Gu S and Zhu X: Succesful use of posterior instrumented spinal fusion alone for scoliosis in 19 patients with neurofibromatosis type-1 followed up for at least 25 months. Arch Orthop Trauma Surg. 129:915–921. 2009.PubMed/NCBI View Article : Google Scholar
60	Ardeleanu V, Chicoş SC, Tutunaru D and Georgescu C: Multiple benign symmetric lipomatosis-a differential diagnosis of obesity. Chirurgia (Bucur). 108:580–583. 2013.PubMed/NCBI
61	Ardeleanu V, Toma A, Pafili K, Papanas N, Motofei I, Diaconu CC, Rizzo M and Stoian AP: Current pharmacological treatment of painful diabetic neuropathy: A narrative review. Medicina (Kaunas). 56(25)2020.PubMed/NCBI View Article : Google Scholar