Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease caused by mutations in the NF1 gene. The disease is characterized by neurofibromatosis, which simultaneously affects multiple systems such as nerves, skin, and bone, and has complex clinical manifestations. Since the National Institutes of Health (NIH) established diagnostic criteria in 1988, the diagnosis and treatment of NF1 have progressed significantly. However, due to the complexity of the disease and the lack of effective treatments, the diagnosis and treatment of NF1 still face many challenges. Strengthening multidisciplinary collaboration, improving and popularizing disease diagnosis and treatment strategies, and developing more effective drugs and treatment methods are the keys to further improve the treatment level of NF1 diseases.
| 1. | Tamura R. Current understanding of neurofibromatosis type 1, 2, and Schwannomatosis. Int J Mol Sci, 2021, 22(11): 5850. doi: 10.3390/ijms22115850. |
| 2. | Gutmann DH, Ferner RE, Listernick RH, et al. Neurofibromatosis type 1. Nat Rev Dis Primers, 2017, 3: 17004. doi: 10.1038/nrdp.2017.4. |
| 3. | Miraglia E, Moliterni E, Iacovino C, et al. Cutaneous manifestations in neurofibromatosis type 1. Clin Ter, 2020, 171(5): e371-e377. |
| 4. | Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet, 2007, 44(2): 81-88. |
| 5. | Ortonne N, Wolkenstein P, Blakeley JO, et al. Cutaneous neurofibromas: Current clinical and pathologic issues. Neurology, 2018, 91(2 Suppl 1): S5-S13. |
| 6. | Wolkenstein P, Zeller J, Revuz J, et al. Quality-of-life impairment in neurofibromatosis type 1: a cross-sectional study of 128 cases. Arch Dermatol, 2001, 137(11): 1421-1425. |
| 7. | Ly KI, Blakeley JO. The diagnosis and management of neurofibromatosis type 1. Med Clin North Am, 2019, 103(6): 1035-1054. |
| 8. | Fisher MJ, Blakeley JO, Weiss BD, et al. Management of neurofibromatosis type 1-associated plexiform neurofibromas. Neuro Oncol, 2022, 24(11): 1827-1844. |
| 9. | Miettinen MM, Antonescu CR, Fletcher CDM, et al. Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1—A consensus overview. Hum Pathol, 2017, 67: 1-10. |
| 10. | Canavese F, Krajbich JI. Resection of plexiform neurofibromas in children with neurofibromatosis type 1. J Pediatr Orthop, 2011, 31(3): 303-311. |
| 11. | Gross AM, Wolters PL, Dombi E, et al. Selumetinib in children with inoperable plexiform neurofibromas. N Engl J Med, 2020, 382(15): 1430-1442. |
| 12. | Reilly KM, Kim A, Blakely J, et al. Neurofibromatosis type 1-associated MPNST state of the science: Outlining a research agenda for the future. J Natl Cancer Inst, 2017, 109(8): djx124. doi: 10.1093/jnci/djx124. |
| 13. | Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol, 2014, 13(8): 834-843. |
| 14. | Walker L, Thompson D, Easton D, et al. A prospective study of neurofibromatosis type 1 cancer incidence in the UK. Br J Cancer, 2006, 95(2): 233-238. |
| 15. | Heervä E, Koffert A, Jokinen E, et al. A controlled register-based study of 460 neurofibromatosis 1 patients: increased fracture risk in children and adults over 41 years of age. J Bone Miner Res, 2012, 27(11): 2333-2337. |
| 16. | White KK, Song KM, Frost N, et al. VEPTRTM growing rods for early-onset neuromuscular scoliosis: feasible and effective. Clin Orthop Relat Res, 2011, 469(5): 1335-1341. |
| 17. | Chauvel-Picard J, Lion-Francois L, Beuriat PA, et al. Craniofacial bone alterations in patients with neurofibromatosis type 1. Childs Nerv Syst, 2020, 36(10): 2391-2399. |
| 18. | Pinna V, Daniele P, Calcagni G, et al. Prevalence, type, and molecular spectrum of NF1 mutations in patients with neurofibromatosis type 1 and congenital heart disease. Genes (Basel), 2019, 10(9): 675. doi: 10.3390/genes10090675. |
| 19. | Nix JS, Blakeley J, Rodriguez FJ. An update on the central nervous system manifestations of neurofibromatosis type 1. Acta Neuropathol, 2020, 139(4): 625-641. |
| 20. | Lehtonen A, Howie E, Trump D, et al. Behaviour in children with neurofibromatosis type 1: cognition, executive function, attention, emotion, and social competence. Dev Med Child Neurol, 2013, 55(2): 111-125. |
| 21. | Friedman JM, Arbiser J, Epstein JA, et al. Cardiovascular disease in neurofibromatosis 1: report of the NF1 cardiovascular task force. Genet Med, 2002, 4(3): 105-111. |
| 22. | Torres Nupan MM, Velez Van Meerbeke A, López Cabra CA, et al. Cognitive and behavioral disorders in children with neurofibromatosis type 1. Front Pediatr, 2017, 5: 227. doi: 10.3389/fped.2017.00227. |
| 23. | Diggs-Andrews KA, Gutmann DH. Modeling cognitive dysfunction in neurofibromatosis-1. Trends Neurosci, 2013, 36(4): 237-247. |
| 24. | Legius E, Messiaen L, Wolkenstein P, et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med, 2021, 23(8): 1506-1513. |
| 25. | Kehrer-Sawatzki H, Cooper DN. Challenges in the diagnosis of neurofibromatosis type 1 (NF1) in young children facilitated by means of revised diagnostic criteria including genetic testing for pathogenic NF1 gene variants. Hum Genet, 2022, 141(2): 177-191. |
| 26. | Cnossen MH, de Goede-Bolder A, van den Broek KM, et al. A prospective 10 year follow up study of patients with neurofibromatosis type 1. Arch Dis Child, 1998, 78(5): 408-412. |
| 27. | DeBella K, Szudek J, Friedman JM. Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics, 2000, 105(3 Pt 1): 608-614. |
| 28. | Brems H, Chmara M, Sahbatou M, et al. Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nat Genet, 2007, 39(9): 1120-1126. |
| 29. | Yasunari T, Shiraki K, Hattori H, et al. Frequency of choroidal abnormalities in neurofibromatosis type 1. Lancet, 2000, 356(9234): 988-992. |
| 30. | Lalvani S, Brown RM. Neurofibromatosis type 1: Optimizing management with a multidisciplinary approach. J Multidiscip Healthc, 2024, 17: 1803-1817. |
| 31. | Poplausky D, Young JN, Tai H, et al. Dermatologic manifestations of neurofibromatosis type 1 and emerging treatments. Cancers (Basel), 2023, 15(10): 2770. doi: 10.3390/cancers15102770. |
| 32. | Wang D, Zhang BH, Wen X, et al. Clinical features and surgical treatments of scoliosis in neurofibromatosis type 1: a systemic review and meta-analysis. Eur Spine J, 2024, 33(7): 2646-2665. |
| 33. | Friedrich RE, Modemann M. Neurofibromatosis type 1-associated plexiform neurofibromas of the face and adjacent head regions: Topography of lesions and surgical treatment data of 179 patients. J Maxillofac Oral Surg, 2023, 22(3): 511-524. |
| 34. | Khalafallah AM, Jimenez AE, Romo CG, et al. Quantifying the utility of a multidisciplinary neuro-oncology tumor board. J Neurosurg, 2020, 135(1): 87-92. |
| 35. | Debs P, Belzberg A, Blakeley J, et al. Multidisciplinary neurofibromatosis conference in the management of patients with neurofibromatosis type 1 and schwannomatosis in a single tertiary care institution. Skeletal Radiol, 2024, 53(5): 909-916. |
| 36. | Miller DT, Freedenberg D, Schorry E, et al. Health supervision for children with neurofibromatosis type 1. Pediatrics, 2019, 143(5): e20190660. doi: 10.1542/peds.2019-0660. |
| 37. | Chen Y, Yu J, Ge S, et al. An overview of optic pathway glioma with neurofibromatosis type 1: Pathogenesis, risk factors, and therapeutic strategies. Invest Ophthalmol Vis Sci, 2024, 65(6): 8. doi: 10.1167/iovs.65.6.8. |
| 38. | 任婷婷, 马建民. 视神经胶质瘤的临床诊疗及研究进展. 中华眼科杂志, 2023, 59(5): 415-419. |
| 39. | Neifert SN, Khan HA, Kurland DB, et al. Management and surgical outcomes of dystrophic scoliosis in neurofibromatosis type 1: a systematic review. Neurosurg Focus, 2022, 52(5): E7. doi: 10.3171/2022.2.FOCUS21790. |
| 40. | Avery RA, Katowitz JA, Fisher MJ, et al. Orbital/periorbital plexiform neurofibromas in children with neurofibromatosis type 1: Multidisciplinary recommendations for care. Ophthalmology, 2017, 124(1): 123-132. |
| 41. | 李作安, 钱长春, 张建民, 等. 腹腔内神经纤维瘤病1型伴发直肠间质瘤1例. 临床肿瘤学杂志, 2018, 23(2): 189-190. |
| 42. | 张志坚, 傅雷华, 周炀, 等. 神经纤维瘤病1型合并慢性髓性白血病一例及文献复习. 浙江中西医结合杂志, 2021, 31(7): 642-644. |
| 43. | 吴凡, 姬辛娜, 沈梦晓, 等. 神经纤维瘤病1型并癫痫发作15例临床特征. 中华儿科杂志, 2023, 61(12): 1124-1128. |
| 44. | Dombi E, Baldwin A, Marcus LJ, et al. Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas. N Engl J Med, 2016, 375(26): 2550-2560. |
| 45. | Weiss BD, Wolters PL, Plotkin SR, et al. NF106: A neurofibromatosis clinical trials consortium phase Ⅱ trial of the MEK inhibitor mirdametinib (PD-0325901) in adolescents and adults with NF1-related plexiform neurofibromas. J Clin Oncol, 2021, 39(7): 797-806. |
| 46. | Fisher MJ, Shih CS, Rhodes SD, et al. Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial. Nat Med, 2021, 27(1): 165-173. |
| 47. | Hu X, Li W, Zeng K, et al. Phase 1 dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of FCN-159 in adults with neurofibromatosis type 1-related unresectable plexiform neurofibromas. BMC Med, 2023, 21(1): 230. doi: 10.1186/s12916-023-02927-2. |
- 1. Tamura R. Current understanding of neurofibromatosis type 1, 2, and Schwannomatosis. Int J Mol Sci, 2021, 22(11): 5850. doi: 10.3390/ijms22115850.
- 2. Gutmann DH, Ferner RE, Listernick RH, et al. Neurofibromatosis type 1. Nat Rev Dis Primers, 2017, 3: 17004. doi: 10.1038/nrdp.2017.4.
- 3. Miraglia E, Moliterni E, Iacovino C, et al. Cutaneous manifestations in neurofibromatosis type 1. Clin Ter, 2020, 171(5): e371-e377.
- 4. Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet, 2007, 44(2): 81-88.
- 5. Ortonne N, Wolkenstein P, Blakeley JO, et al. Cutaneous neurofibromas: Current clinical and pathologic issues. Neurology, 2018, 91(2 Suppl 1): S5-S13.
- 6. Wolkenstein P, Zeller J, Revuz J, et al. Quality-of-life impairment in neurofibromatosis type 1: a cross-sectional study of 128 cases. Arch Dermatol, 2001, 137(11): 1421-1425.
- 7. Ly KI, Blakeley JO. The diagnosis and management of neurofibromatosis type 1. Med Clin North Am, 2019, 103(6): 1035-1054.
- 8. Fisher MJ, Blakeley JO, Weiss BD, et al. Management of neurofibromatosis type 1-associated plexiform neurofibromas. Neuro Oncol, 2022, 24(11): 1827-1844.
- 9. Miettinen MM, Antonescu CR, Fletcher CDM, et al. Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1—A consensus overview. Hum Pathol, 2017, 67: 1-10.
- 10. Canavese F, Krajbich JI. Resection of plexiform neurofibromas in children with neurofibromatosis type 1. J Pediatr Orthop, 2011, 31(3): 303-311.
- 11. Gross AM, Wolters PL, Dombi E, et al. Selumetinib in children with inoperable plexiform neurofibromas. N Engl J Med, 2020, 382(15): 1430-1442.
- 12. Reilly KM, Kim A, Blakely J, et al. Neurofibromatosis type 1-associated MPNST state of the science: Outlining a research agenda for the future. J Natl Cancer Inst, 2017, 109(8): djx124. doi: 10.1093/jnci/djx124.
- 13. Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol, 2014, 13(8): 834-843.
- 14. Walker L, Thompson D, Easton D, et al. A prospective study of neurofibromatosis type 1 cancer incidence in the UK. Br J Cancer, 2006, 95(2): 233-238.
- 15. Heervä E, Koffert A, Jokinen E, et al. A controlled register-based study of 460 neurofibromatosis 1 patients: increased fracture risk in children and adults over 41 years of age. J Bone Miner Res, 2012, 27(11): 2333-2337.
- 16. White KK, Song KM, Frost N, et al. VEPTRTM growing rods for early-onset neuromuscular scoliosis: feasible and effective. Clin Orthop Relat Res, 2011, 469(5): 1335-1341.
- 17. Chauvel-Picard J, Lion-Francois L, Beuriat PA, et al. Craniofacial bone alterations in patients with neurofibromatosis type 1. Childs Nerv Syst, 2020, 36(10): 2391-2399.
- 18. Pinna V, Daniele P, Calcagni G, et al. Prevalence, type, and molecular spectrum of NF1 mutations in patients with neurofibromatosis type 1 and congenital heart disease. Genes (Basel), 2019, 10(9): 675. doi: 10.3390/genes10090675.
- 19. Nix JS, Blakeley J, Rodriguez FJ. An update on the central nervous system manifestations of neurofibromatosis type 1. Acta Neuropathol, 2020, 139(4): 625-641.
- 20. Lehtonen A, Howie E, Trump D, et al. Behaviour in children with neurofibromatosis type 1: cognition, executive function, attention, emotion, and social competence. Dev Med Child Neurol, 2013, 55(2): 111-125.
- 21. Friedman JM, Arbiser J, Epstein JA, et al. Cardiovascular disease in neurofibromatosis 1: report of the NF1 cardiovascular task force. Genet Med, 2002, 4(3): 105-111.
- 22. Torres Nupan MM, Velez Van Meerbeke A, López Cabra CA, et al. Cognitive and behavioral disorders in children with neurofibromatosis type 1. Front Pediatr, 2017, 5: 227. doi: 10.3389/fped.2017.00227.
- 23. Diggs-Andrews KA, Gutmann DH. Modeling cognitive dysfunction in neurofibromatosis-1. Trends Neurosci, 2013, 36(4): 237-247.
- 24. Legius E, Messiaen L, Wolkenstein P, et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med, 2021, 23(8): 1506-1513.
- 25. Kehrer-Sawatzki H, Cooper DN. Challenges in the diagnosis of neurofibromatosis type 1 (NF1) in young children facilitated by means of revised diagnostic criteria including genetic testing for pathogenic NF1 gene variants. Hum Genet, 2022, 141(2): 177-191.
- 26. Cnossen MH, de Goede-Bolder A, van den Broek KM, et al. A prospective 10 year follow up study of patients with neurofibromatosis type 1. Arch Dis Child, 1998, 78(5): 408-412.
- 27. DeBella K, Szudek J, Friedman JM. Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics, 2000, 105(3 Pt 1): 608-614.
- 28. Brems H, Chmara M, Sahbatou M, et al. Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nat Genet, 2007, 39(9): 1120-1126.
- 29. Yasunari T, Shiraki K, Hattori H, et al. Frequency of choroidal abnormalities in neurofibromatosis type 1. Lancet, 2000, 356(9234): 988-992.
- 30. Lalvani S, Brown RM. Neurofibromatosis type 1: Optimizing management with a multidisciplinary approach. J Multidiscip Healthc, 2024, 17: 1803-1817.
- 31. Poplausky D, Young JN, Tai H, et al. Dermatologic manifestations of neurofibromatosis type 1 and emerging treatments. Cancers (Basel), 2023, 15(10): 2770. doi: 10.3390/cancers15102770.
- 32. Wang D, Zhang BH, Wen X, et al. Clinical features and surgical treatments of scoliosis in neurofibromatosis type 1: a systemic review and meta-analysis. Eur Spine J, 2024, 33(7): 2646-2665.
- 33. Friedrich RE, Modemann M. Neurofibromatosis type 1-associated plexiform neurofibromas of the face and adjacent head regions: Topography of lesions and surgical treatment data of 179 patients. J Maxillofac Oral Surg, 2023, 22(3): 511-524.
- 34. Khalafallah AM, Jimenez AE, Romo CG, et al. Quantifying the utility of a multidisciplinary neuro-oncology tumor board. J Neurosurg, 2020, 135(1): 87-92.
- 35. Debs P, Belzberg A, Blakeley J, et al. Multidisciplinary neurofibromatosis conference in the management of patients with neurofibromatosis type 1 and schwannomatosis in a single tertiary care institution. Skeletal Radiol, 2024, 53(5): 909-916.
- 36. Miller DT, Freedenberg D, Schorry E, et al. Health supervision for children with neurofibromatosis type 1. Pediatrics, 2019, 143(5): e20190660. doi: 10.1542/peds.2019-0660.
- 37. Chen Y, Yu J, Ge S, et al. An overview of optic pathway glioma with neurofibromatosis type 1: Pathogenesis, risk factors, and therapeutic strategies. Invest Ophthalmol Vis Sci, 2024, 65(6): 8. doi: 10.1167/iovs.65.6.8.
- 38. 任婷婷, 马建民. 视神经胶质瘤的临床诊疗及研究进展. 中华眼科杂志, 2023, 59(5): 415-419.
- 39. Neifert SN, Khan HA, Kurland DB, et al. Management and surgical outcomes of dystrophic scoliosis in neurofibromatosis type 1: a systematic review. Neurosurg Focus, 2022, 52(5): E7. doi: 10.3171/2022.2.FOCUS21790.
- 40. Avery RA, Katowitz JA, Fisher MJ, et al. Orbital/periorbital plexiform neurofibromas in children with neurofibromatosis type 1: Multidisciplinary recommendations for care. Ophthalmology, 2017, 124(1): 123-132.
- 41. 李作安, 钱长春, 张建民, 等. 腹腔内神经纤维瘤病1型伴发直肠间质瘤1例. 临床肿瘤学杂志, 2018, 23(2): 189-190.
- 42. 张志坚, 傅雷华, 周炀, 等. 神经纤维瘤病1型合并慢性髓性白血病一例及文献复习. 浙江中西医结合杂志, 2021, 31(7): 642-644.
- 43. 吴凡, 姬辛娜, 沈梦晓, 等. 神经纤维瘤病1型并癫痫发作15例临床特征. 中华儿科杂志, 2023, 61(12): 1124-1128.
- 44. Dombi E, Baldwin A, Marcus LJ, et al. Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas. N Engl J Med, 2016, 375(26): 2550-2560.
- 45. Weiss BD, Wolters PL, Plotkin SR, et al. NF106: A neurofibromatosis clinical trials consortium phase Ⅱ trial of the MEK inhibitor mirdametinib (PD-0325901) in adolescents and adults with NF1-related plexiform neurofibromas. J Clin Oncol, 2021, 39(7): 797-806.
- 46. Fisher MJ, Shih CS, Rhodes SD, et al. Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial. Nat Med, 2021, 27(1): 165-173.
- 47. Hu X, Li W, Zeng K, et al. Phase 1 dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of FCN-159 in adults with neurofibromatosis type 1-related unresectable plexiform neurofibromas. BMC Med, 2023, 21(1): 230. doi: 10.1186/s12916-023-02927-2.