Cao Jun,Li Haichong.Clinical diagnostics and interventions of children with neurofibromatosis type 1 associated scoliosis[J].Journal of Clinical Pediatric Surgery,2025,(04):301-306.[doi:10.3760/cma.j.cn101785-202412060-001]
儿童Ⅰ型神经纤维瘤病脊柱侧弯的诊治要点
- Title:
- Clinical diagnostics and interventions of children with neurofibromatosis type 1 associated scoliosis
- Keywords:
- Neurofibromatosis Type 1; Scoliosis; Diagnosis; Surgical Procedures; Operative; Conservative Treatment; Drug Therapy; Multi－disciplinary Team; Child
- 摘要:
- Ⅰ型神经纤维瘤病（neurofibromatosis type 1,NF1）的临床表现复杂多样，患者可以出现牛奶咖啡斑，丛状神经纤维瘤，骨骼系统畸形等，其中脊柱侧弯是最常见的骨骼合并畸形。儿童NF1脊柱侧弯常伴随脊柱骨骼营养不良性改变，此类脊柱侧弯发病早，进展快，在造成患者外观畸形的同时，还影响脊柱的正常生长发育，应早期进行干预。可根据脊柱侧弯的部位，类型，程度，结合患者年龄和生长潜力，选择合适的治疗方式。在治疗脊柱侧弯的同时，需要注意合并畸形的处理及预防并发症。NF1脊柱侧弯在整体管理过程中，需要加强多学科联合，力争给患者提供规范化，个体化，精细化的治疗。
- Abstract:
- Children of type 1 neurofibromatosis may present with a wide range of symptoms,including café au lait spots,plexiform neurofibromas and skeletal system deformities.Among them,scoliosis is the most common skeletal deformity.Children with NF1 scoliosis often have nutritional deficiency-type changes in spinal bones,leading to early onset and rapid progression of scoliosis,causing deformity of appearance and affecting normal growth and development of spine.Thus early intervention is necessary.Based on the location,type,degree of scoliosis,and patient age and growth potential,appropriate treatments may be selected.In addition to treating scoliosis,attention should also be paid to managing concomitant deformities and preventing complications.For overall management of NF1,multidisciplinary treatment is needed to provide standardized,individual- ized and meticulous treatment.
参考文献/References:
[1] Lee TJ,Chopra M,Kim RH,et al.Incidence and prevalence of neurofibromatosis type 1 and 2:a systematic review and meta-analysis[J].Orpha-net J Rare Dis,2023,18(1):292.DOI:10.1186/s13023-023-02911-2.
[2] Cimino PJ,Gutmann DH.Neurofibromatosis type 1[J].Handb Clin Neurol,2018,148:799-811.DOI:10.1016/B978-0-444-64076-5.00051-X.
[3] Bianchessi D,Ibba MC,Saletti V,et al.Simultaneous detection of NF1,SPRED1,LZTR1,and NF2 gene mutations by targeted NGS in an Italian cohort of suspected NF1 patients[J].Genes (Basel),2020,11(6):671.DOI:10.3390/genes11060671.
[4] Xu AL,Suresh KV,Gomez JA,et al.Consensus-based best practice guidelines for the management of spinal deformity and associated tumors in pe-diatric neurofibromatosis type 1:screening and surveillance,surgical intervention,and medical therapy[J].J Pediatr Orthop,2023,43(7):e531-e537.DOI:10.1097/BPO. 0000000000002431.
[5] Lu YT,Rejiepu B,Zhang D,et al.Childhood-onset refractory hypertension results from neurofibromatosis type 1 caused by a splicing NF1 mutation[J].Kidney Blood Press Res,2023,48(1):568-577.DOI:10.1159/000533144.
[6] Cimino PJ,Ketchum C,Turakulov R,et al.Expanded analysis of high-grade astrocytoma with piloid features identifies an epigenetically and clini-cally distinct subtype associated with neurofibromatosis type 1[J].Acta Neuropathol,2023,145(1):71-82.DOI:10.1007/s00401-022-02513-5.
[7] Wang ZC,Huang JX,Li QF.Selumetinib for plexiform neurofibroma:advances and ongoing challenges[J].Neuro Oncol,2024,26(12):2391-2393.DOI:10.1093/neuonc/noael80.
[8] Han YH,Li BY,Yu XK,et al.Efficacy and safety of selumetinib in patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas:a systematic review and meta-analysis[J].J Neurol,2024,271(5):2379-2389.DOI:10.1007/s00415-024-12301-8.
[9] 中国罕见病联盟I型神经纤维瘤病多学科诊疗协作组.I型神经纤维瘤病多学科诊治指南(2023版)[J].罕见病研究,2023,2(2):210-230.DOI:10.12376/j.issn.2097-0501.2023.02.009.Multidisciplinary Diagnosis and Treatment Collaboration Group for Neurofibromatosis Type 1 of China Alliance for Rare Diseases.Guidelines for multidisciplinary diagnosis and treatment of neurofibromatosis type 1(Edition 2023)[J].J Rare Dis,2023,2(2):210-230.DOI:10.12376/j. issn.2097-0501.2023.02.009.
[10] Giugliano T,Santoro C,Torella A,et al.Clinical and genetic findings in children with neurofibromatosis type 1,Legius syndrome,and other related neurocutaneous disorders[J].Genes (Basel),2019,10(8):580.DOI:10.3390/genes10080580.
[11] 李方财,张宁,陈维善,等.生长棒治疗I型神经纤维瘤病早发性脊柱侧凸[J].中国脊柱脊髓杂志,2017,27(6):501-505.DOI:10.3969/j.issn.1004-406X.2017.06.05.Li FC,Zhang N,Chen WS,et al.Use of growing rods in the treatment of early onset scoliosis with type 1 neurofibromatosis[J].Chin J Spine Spinal Cord,2017,27(6):501-505.DOI:10.3969/j.issn.1004-406X.2017.06.05.
[12] Winter RB,Moe JH,Bradford DS,et al.Spine deformity in neurofibromatosis.A review of one hundred and two patients[J].J Bone Joint Surg Am, 1979,61(5):677-694.
[13] Jain VV,Berry CA,Crawford AH,et al.Growing rods are an effective fusionless method of controlling early-onset scoliosis associated with neurofi-bromatosis type 1(NF1):a multicenter retrospective case series[J].J Pediatr Orthop,2017, 37(8):e612-e618.DOI:10.1097/BPO. 0000000000000963.
[14] 祁新禹,张学军,白云松,等.凸侧短段固定凹侧生长棒技术治疗小儿神经纤维瘤病脊柱侧弯[J].临床小儿外科杂志,2015,14(4):271-274.DOI:10.3969/j.issn.1671-6353.2015.04.005.Qi XY,Zhang XJ,Bai YS,et al.Treating scoliosis caused by neurofibromatosis with brief fixing on convex side plus growing rod on concave side[J].J Clin Ped Sur,2015,14(4):271-274.DOI:10.3969/j.issn.1671-6353.2015.04.005.
[15] Heflin JA,Cleveland A,Ford SD,et al.Use of rib-based distraction in the treatment of early-onset scoliosis associated with neurofibromatosis type 1 in the young child[J].Spine Deform,2015,3(3):239-245.DOI:10.1016/j.jspd.2014.10.003.
[16] 杨阳,仉建国,沈建雄,等.双生长棒技术治疗早发性I型神经纤维瘤病营养不良型脊柱侧凸的疗效分析[J].中国脊柱脊髓杂志,2017, 27(6):495-500.DOI:10.3969/j.issn.1004-406X.2017.06.04.Yang Y,Zhang JG,Shen JX,et al.Efficacy of dual growing rod technique in the treatment of early onset dystrophic scoliosis with neurofibromatosis type 1[J].Chin J Spine Spinal Cord,2017,27(6):495-500.DOI:10.3969/j.issn.1004-406X.2017.06.04.
[17] Yao ZM, Guo D, Li H, et al. Surgical treatment of dystrophic scoliosis in neurofibromatosis type 1:outcomes and complications[J]. Clin Spine Surg,2019,32(1):E50-E55. DOI:10. 1097/BSD. 0000000000000716.
[18] Wang ZY, Fu CF, Leng JL, et al. Treatment of dystrophic scoliosis in neurofibromatosis type 1 with one-stage posterior pedicle screw technique[J]. Spine J, 2015, 15(4):587-595. DOI:10. 1016/j. spinee. 2014. 10. 014.
[19] Tauchi R,Kawakami N, Castro MA, et al. Long-term surgical outcomes after early definitive spinal fusion for early-onset scoliosis with neurofibromatosis type 1 at mean follow-up of 14 years[J]. J Pediatr Orthop, 2020, 40(1):42-47. DOI:10. 1097/BPO. 00000000000001090.
[20] Mladenov KV, Spiro AS, Krajewski KL, et al. Management of spinal deformities and tibial pseudarthrosis in children with neurofibromatosis type 1(NF-1)[J]. Childs Nerv Syst, 2020, 36(10):2409-2425. DOI:10. 1007/s00381-020-04775-4.
[21] Xu EJ, Gao R, Jiang H, et al. Combined halo gravity traction and dual growing rod technique for the treatment of early onset dystrophic scoliosis in neurofibromatosis type 1[J]. World Neurosurg, 2019, 126:e173-e180. DOI:10. 1016/j. wneu. 2019.01. 290.
[22] Barreto-Duarte B, Andrade-Gomes FH, Arriaga MB, et al. Association between neurofibromatosis type 1 and cerebrovascular diseases in children:a systematic review[J]. PLoS One,2021,16(1):e0241096. DOI:10. 1371/journal. pone. 0241096.
[23] Wang ZY, Liu Y. Research update and recent developments in the management of scoliosis in neurofibromatosis type 1[J]. Orthopedics, 2010,33(5):335-341. DOI:10.3928/01477447-20100329-20.
[24] Yang Z, Liu Y, Qi LT, et al. Does preoperative halo-gravity traction reduce the degree of deformity and improve pulmonary function in severe scoliosis patients with pulmonary insufficiency?A systematic review and meta-analysis[J]. Front Med (Lausanne), 2021, 8:767238. DOI:10.3389/fmed. 2021.767238.
[25] Wang JQ, Han B, Hai Y, et al. How helpful is the halo-gravity traction in severe spinal deformity patients?:A systematic review and meta-analysis[J]. Eur Spine J, 2021, 30(11):3162-3171. DOI:10. 1007/s00586-021-06902-4.
[26] Shimizu T, Lenke LG, Cerpa M, et al. Preoperative halo-gravity traction for treatment of severe adult kyphosis and scoliosis[J]. Spine Deform, 2020,8(1):85-95. DOI:10. 1007/s43390-019-00017-z.
[27] Yang CS, Wang HF, Zheng ZM, et al. Halo-gravity traction in the treatment of severe spinal deformity:a systematic review and meta-analysis[J]. Eur Spine J, 2017, 26(7):1810-1816. DOI:10. 1007/s00586-016-4848-y.
[28] Bao HD, Yan P, Bao MK, et al. Halo-gravity traction combined with assisted ventilation:an effective pre-operative management for severe adult scoliosis complicated with respiratory dysfunction[J]. Eur Spine J, 2016,25(8):2416-2422. DOI:10. 1007/s00586-016-4607-0.
[29] Gross AM, O’Sullivan Coyne G, Dombi E, et al. Selumetinib in adults with NF1 and inoperable plexiform neurofibroma:a phase 2 trial[J]. Nat Med,2025,31(1):105-115. DOI:10. 1038/s41591-024-03361-4.
[30] Gross AM, Wolters PL, Dombi E, et al. Selumetinib in children with inoperable plexiform neurofibromas[J]. N Engl J Med, 2020, 382(15):1430-1442. DOI:10. 1056/NEJMoa1912735.
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备注/Memo
收稿日期:2024-12-25。
基金项目:北京市自然科学基金-海淀原始创新联合基金资助项目（L222095）;国家重点研发计划资助（2023YFC2507701）
通讯作者:曹隽,Email:caojunhere@yeah.com