A Comprehensive Overview of NF1 Mutations in Iranian Patients.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in the NF1 gene. This disorder shows nearly complete penetrance and high phenotypic variability. We used the whole-exome sequencing technique to identify mutations in 32 NF1 cases from 22 Iranian families. A total of 31 variants, including 30 point mutations and one large deletion, were detected. In eight cases, variants were inherited, while they were sporadic in the remaining. Seven novel variants, including c.5576 T > G, c.6658_6659insC, c.2322dupT, c.92_93insAA, c.4360C > T, c.3814C > T, and c.4565_4566delinsC, were identified. The current study is the largest in terms of the sample size of Iranian NF1 cases with identified mutations. The results can broaden the spectrum of NF1 mutations and facilitate the process of genetic counseling in the affected families.

Jaffe-Campanacci syndrome; a case series and review of the literature.

BACKGROUND: Jaffe-Campanacci syndrome is a rare syndrome, characterized by multiple non-ossifying fibromas (NOF) and cafe-au-lait patches. The name was coined in 1982 by Mirra after Jaffe who first described the case in 1958. Although it's suggested there is a relation with Neurofibromatosis type 1, there is still no consensus on whether Jaffe-Campanacci syndrome is a subtype or variant of neurofibromatosis-1(NF-1). CASE PRESENTATION: In this article, we present a case series of 2 patients. The first case is a 13-year-old male with Jaffe-Campanacci syndrome who presented with a distal femur fracture. His father had positive features of both Jaffe-Campanacci syndrome and NF-1, while his sister only had features of NF-1, so we presented both. CONCLUSION: Jaffe-Campanacci has a clear relationship with type 1 neurofibromatosis, which still has to be genetically established. Due to the presence of several large non-ossifying fibromas of the long bones, it is linked to a significant risk of pathological fractures. We concur with previous authors, that an osseous screening program should be performed for all patients with newly diagnosed type 1 neurofibromatosis, to identify non-ossifying fibromas and assess the potential for pathological fracture. Moreover, siblings of patients with NF-1 should be screened for multiple NOFs that may carry a high risk of pathological fractures.

MEK-SHP2 inhibition prevents tibial pseudarthrosis caused by NF1 loss in Schwann cells and skeletal stem/progenitor cells.

Congenital pseudarthrosis of the tibia (CPT) is a severe pathology marked by spontaneous bone fractures that fail to heal, leading to fibrous nonunion. Half of patients with CPT are affected by the multisystemic genetic disorder neurofibromatosis type 1 (NF1) caused by mutations in the NF1 tumor suppressor gene, a negative regulator of RAS-mitogen-activated protein kinase (MAPK) signaling pathway. Here, we analyzed patients with CPT and Prss56-Nf1 knockout mice to elucidate the pathogenic mechanisms of CPT-related fibrous nonunion and explored a pharmacological approach to treat CPT. We identified NF1-deficient Schwann cells and skeletal stem/progenitor cells (SSPCs) in pathological periosteum as affected cell types driving fibrosis. Whereas NF1-deficient SSPCs adopted a fibrotic fate, NF1-deficient Schwann cells produced critical paracrine factors including transforming growth factor-ß and induced fibrotic differentiation of wild-type SSPCs. To counteract the elevated RAS-MAPK signaling in both NF1-deficient Schwann cells and SSPCs, we used MAPK kinase (MEK) and Src homology 2 containing protein tyrosine phosphatase 2 (SHP2) inhibitors. Combined MEK-SHP2 inhibition in vivo prevented fibrous nonunion in the Prss56-Nf1 knockout mouse model, providing a promising therapeutic strategy for the treatment of fibrous nonunion in CPT.

Genetic/epigenetic effects in NF1 microdeletion syndrome: beyond the haploinsufficiency, looking at the contribution of not deleted genes.

NF1 microdeletion syndrome, accounting for 5-11% of NF1 patients, is caused by a deletion in the NF1 region and it is generally characterized by a severe phenotype. Although 70% of NF1 microdeletion patients presents the same 1.4 Mb type-I deletion, some patients may show additional clinical features. Therefore, the contribution of several pathogenic mechanisms, besides haploinsufficiency of some genes within the deletion interval, is expected and needs to be defined. We investigated an altered expression of deletion flanking genes by qPCR in patients with type-1 NF1 deletion, compared to healthy donors, possibly contributing to the clinical traits of NF1 microdeletion syndrome. In addition, the 1.4-Mb deletion leads to changes in the 3D chromatin structure in the 17q11.2 region. Specifically, this deletion alters DNA-DNA interactions in the regions flanking the breakpoints, as demonstrated by our 4C-seq analysis. This alteration likely causes position effect on the expression of deletion flanking genes.Interestingly, 4C-seq analysis revealed that in microdeletion patients, an interaction was established between the RHOT1 promoter and the SLC6A4 gene, which showed increased expression. We performed NGS on putative modifier genes, and identified two "likely pathogenic" rare variants in RAS pathway, possibly contributing to incidental phenotypic features.This study provides new insights into understanding the pathogenesis of NF1 microdeletion syndrome and suggests a novel pathomechanism that contributes to the expression phenotype in addition to haploinsufficiency of genes located within the deletion.This is a pivotal approach that can be applied to unravel microdeletion syndromes, improving precision medicine, prognosis and patients' follow-up.

Reconstruction of congenital pseudarthrosis of the radius with a vascularized tibial periosteal transplant: A case report.

Congenital pseudarthrosis of the forearm poses a considerable challenge because of its rarity. The objective of this report is to introduce a novel surgical technique for its treatment. Here, we document a case of congenital pseudarthrosis of the radius in a 3-year-old boy diagnosed with type-1 neurofibromatosis. The surgical treatment involved the excision of approximately 9 cm of native radial periosteum and a bifocal radius osteotomy, which was supplemented with a vascularized tibial periosteal transplant to facilitate bone healing. Anastomosis between the anterior tibial vessels and radial vessels was performed. No immediate or late postoperative complications were observed. After 3 weeks, a robust callus formation was observed, and during a follow-up examination 3 years and 4 months later, a wide range of active forearm rotation was noted. This report suggests that vascularized periosteal flaps show promise as a viable treatment option for congenital pseudarthrosis of the forearm. They offer an alternative to vascularized fibular grafts or single-bone forearm constructs.

Selumetinib for children with neurofibromatosis type 1 and plexiform neurofibromas: A plain language summary of SPRINT.

WHAT IS THIS SUMMARY ABOUT?: This summary describes a publication about a study called SPRINT. The SPRINT study included 50 children with neurofibromatosis type 1 (NF1) and plexiform neurofibroma (PN) that could not be removed with surgery. PNs are tumors that grow along nerves and can cause various problems for children, such as pain, changes to appearance, and muscle weakness. In SPRINT, the study team wanted to learn whether a medication called selumetinib was able to shrink the PN caused by NF1 (also known as NF1-related PN), and if shrinking PNs helped relieve children of the problems caused by it. To assess how selumetinib might help, children had scans to measure the size of their PN, completed questionnaires, and had a variety of other tests done by their doctor. Their caregivers also completed questionnaires about their child. The children took selumetinib capsules twice a day on an empty stomach. WHAT WERE THE RESULTS?: The results showed that selumetinib was able to shrink the PN for most children (68%). The results also showed that the problems caused by the children's PNs mostly improved while on selumetinib treatment. SPRINT also showed that the side effects of selumetinib were mainly mild and could be managed by doctors. WHAT DO THE RESULTS MEAN?: Before SPRINT, there were not many treatment options for children with NF1 and PN as there were no medications that had been shown to shrink PN, and surgery was not always possible. SPRINT showed that this medication shrinks most PNs and could help children with NF1 and PN. In April 2020, selumetinib was approved by the US Food and Drug Administration (FDA) because of the results of SPRINT. Selumetinib was the first and, as of February 2024, is the only medicine that can be prescribed by doctors to help children with NF1-related PN. Clinical Trial Registration: NCT01362803 (SPRINT) (ClinicalTrials.gov).

Vesicourachal Diverticulum: An Uncommon Incidental Finding on Staging 18F-FDG PET/CT in a Patient with Suspected Malignant Transformation of Neurofibromatosis.

In a 32-y-old man with neurofibromatosis type 1, 18F-FDG PET/CT incidentally revealed a vesicourachal diverticulum, a rare anatomic variant. The PET/CT, performed for staging a malignant peripheral nerve sheath tumor, highlighted a distinctive 18F-FDG-avid pattern crucial for accurate diagnosis. Recognizing such features enhances disease assessment and clarifies distinctions between benign urogenital anomalies and malignancies in 18F-FDG PET/CT staging.

Guided Growth to Treat Anterolateral Tibial Bowing Associated with Congenital Pseudarthrosis of the Tibia.

BACKGROUND: Anterolateral tibial bowing associated with congenital tibial pseudarthrosis occurs often in patients with neurofibromatosis type 1 and results from the inability of the fractured bone to unite, leading to persistent nonunion, abnormal bone growth, and further bowing of the tibia. Current surgical and nonsurgical approaches demonstrate persistent nonunion or refracture, often resulting in amputation. METHODS: This report describes the management of 3 patients with anterolateral tibial bowing and NF1 who underwent distal tibia-guided growth. RESULTS: The patients had an average age of 1.6 years at initial operation, with a total of 3 to 4 surgeries over an average of 2.1 years. The latest follow-up on all patients is included, at a mean of 5.1 years after the initial operation. All 3 patients experienced substantial functional improvement and improved alignment of the mechanical axis of the tibia. One patient has experienced refracture. CONCLUSIONS: Our study indicates that guided growth can serve as an additional surgical option to improve ALTB and potentially reduce the risk of fracture and pseudarthrosis by restoring normal mechanical alignment. LEVEL OF EVIDENCE: Level-IV, Case Series.

An Overview of Optic Pathway Glioma With Neurofibromatosis Type 1: Pathogenesis, Risk Factors, and Therapeutic Strategies.

Optic pathway gliomas (OPGs) are most predominant pilocytic astrocytomas, which are typically diagnosed within the first decade of life. The majority of affected children with OPGs also present with neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome. OPGs in individuals with NF1 primarily affect the optic pathway and lead to visual disturbance. However, it is challenging to assess risk in asymptomatic patients without valid biomarkers. On the other hand, for symptomatic patients, there is still no effective treatment to prevent or recover vision loss. Therefore, this review summarizes current knowledge regarding the pathogenesis of NF1-associated OPGs (NF1-OPGs) from preclinical studies to seek potential prognostic markers and therapeutic targets. First, the loss of the NF1 gene activates 3 distinct Ras effector pathways, including the PI3K/AKT/mTOR pathway, the MEK/ERK pathway, and the cAMP pathway, which mediate glioma tumorigenesis. Meanwhile, non-neoplastic cells from the tumor microenvironment (microglia, T cells, neurons, etc.) also contribute to gliomagenesis via various soluble factors. Subsequently, we investigated potential genetic risk factors, molecularly targeted therapies, and neuroprotective strategies for tumor prevention and vision recovery. Last, potential directions and promising preclinical models of NF1-OPGs are presented for further research. On the whole, NF1-OPGs develop as a result of the interaction between glioma cells and the tumor microenvironment. Developing effective treatments require a better understanding of tumor molecular characteristics, as well as multistage interventions targeting both neoplastic cells and non-neoplastic cells.

Revisiting the NPcis mouse model: A new tool to model plexiform neurofibroma.

Neurofibromatosis Type I (NF1) is a rare genetic disorder. NF1 patients frequently develop a benign tumor in peripheral nerve plexuses called plexiform neurofibroma. In the past two decades, tissue-specific Nf1 knockout mouse models were developed using commercially available tissue-specific Cre recombinase and the Nf1 flox mice to mimic neurofibroma development. However, these models develop para-spinal neurofibroma, recapitulating a rare type of neurofibroma found in NF1 patients. The NPcis mouse model developed a malignant version of neurofibroma called malignant peripheral nerve sheath tumor (MPNST) within 3 to 6 months but intriguingly without apparent benign precursor lesion. Here, we revisited the NPcis model and discovered that about 20% display clinical signs similar to Nf1 tissue-specific knockout mice models. However, a systematic histological analysis could not explain the clinical signs we observed although we noticed lesions reminiscent of a neurofibroma in a peripheral nerve, a cutaneous neurofibroma, and para-spinal neurofibroma on rare occasions in NPcis mice. We also observed that 10% of the mice developed a malignant peripheral nerve sheath tumor (MPNST) spontaneously, coinciding with their earring tag identification. Strikingly, half of the sciatic nerves from NPcis mice developed plexiform neurofibroma within 1-6 months when intentionally injured. Thus, we provided a procedure to turn the widely used NPcis sarcoma model into a model recapitulating plexiform neurofibroma.

Inflammatory rhabdomyoblastic tumor, pheochromocytoma, and pulmonary hamartoma in a patient with neurofibromatosis type 1: a case report.

BACKGROUND: Inflammatory rhabdomyoblastic tumors are relatively recently recognized soft tissue tumors with a low malignant potential. Here, we present a case of concurrent inflammatory rhabdomyoblastic tumor (IRMT), adrenal pheochromocytoma, and pulmonary hamartoma in a patient with neurofibromatosis type 1 (NF1). To our knowledge, this is the first time that this constellation of tumors has been described in the literature. CASE PRESENTATION: A female patient in her late 20s with known NF1 was diagnosed with an inflammatory rhabdomyoblastic tumor, pheochromocytoma, and pulmonary hamartoma in a short succession. IRMT was found to harbor a near-haploid genome and displayed a typical immunohistochemical profile as well as a focal aberrant p53 expression pattern. CONCLUSIONS: This case report strengthens the theory that defects in the tumor suppressor NF1 play a central role in the pathogenesis of inflammatory rhabdomyoblastic tumors and that IRMT may be part of the spectrum of neurofibromatosis type 1 related tumors.

Concurrent Collection of Fetal Murine Brain and Serum to Assess Effects of Maternal Diet on Nutrition and Neurodevelopment in Neurofibromatosis Type 1.

Maternal diet-induced obesity has been demonstrated to alter neurodevelopment in offspring, which may lead to reduced cognitive capacity, hyperactivity, and impairments in social behavior. Patients with the clinically heterogeneous genetic disorder Neurofibromatosis Type 1 (NF1) may present with similar deficits, but it is currently unclear whether environmental factors such as maternal diet influence the development of these phenotypes, and if so, the mechanism by which such an effect would occur. To enable evaluation of how maternal obesogenic diet exposure affects systemic factors relevant to neurodevelopment in NF1, we have developed a method to simultaneously collect non-hemolyzed serum and whole or regionally micro-dissected brains from fetal offspring of murine dams fed a control diet versus a high-fat, high-sucrose diet. Brains were processed for cryosectioning or flash frozen to use for subsequent RNA or protein isolation; the quality of the collected tissue was verified by immunostaining. The quality of the serum was verified by analyzing macronutrient profiles. Using this technique, we have identified that maternal obesogenic diet increases fetal serum cholesterol similarly between WT and Nf1-heterozygous pups.

snRNA-seq of human cutaneous neurofibromas before and after selumetinib treatment implicates role of altered Schwann cell states, inter-cellular signaling, and extracellular matrix in treatment response.

Neurofibromatosis Type 1 (NF1) is caused by loss of function variants in the NF1 gene. Most patients with NF1 develop skin lesions called cutaneous neurofibromas (cNFs). Currently the only approved therapeutic for NF1 is selumetinib, a mitogen -activated protein kinase (MEK) inhibitor. The purpose of this study was to analyze the transcriptome of cNF tumors before and on selumetinib treatment to understand both tumor composition and response. We obtained biopsy sets of tumors both pre- and on- selumetinib treatment from the same individuals and were able to collect sets from four separate individuals. We sequenced mRNA from 5844 nuclei and identified 30,442 genes in the untreated group and sequenced 5701 nuclei and identified 30,127 genes in the selumetinib treated group. We identified and quantified distinct populations of cells (Schwann cells, fibroblasts, pericytes, myeloid cells, melanocytes, keratinocytes, and two populations of endothelial cells). While we anticipated that cell proportions might change with treatment, we did not identify any one cell population that changed significantly, likely due to an inherent level of variability between tumors. We also evaluated differential gene expression based on drug treatment in each cell type. Ingenuity pathway analysis (IPA) was also used to identify pathways that differ on treatment. As anticipated, we identified a significant decrease in ERK/MAPK signaling in cells including Schwann cells but most specifically in myeloid cells. Interestingly, there is a significant decrease in opioid signaling in myeloid and endothelial cells; this downward trend is also observed in Schwann cells and fibroblasts. Cell communication was assessed by RNA velocity, Scriabin, and CellChat analyses which indicated that Schwann cells and fibroblasts have dramatically altered cell states defined by specific gene expression signatures following treatment (RNA velocity). There are dramatic changes in receptor-ligand pairs following treatment (Scriabin), and robust intercellular signaling between virtually all cell types associated with extracellular matrix (ECM) pathways (Collagen, Laminin, Fibronectin, and Nectin) is downregulated after treatment. These response specific gene signatures and interaction pathways could provide clues for understanding treatment outcomes or inform future therapies.

Multimodal Imaging Characteristics and Diagnostic Value of Choroidal Nodules in Patients with Neurofibromatosis Type 1.

Objectives: Yasunari nodules are choroidal lesions observed in patients diagnosed with neurofibromatosis type 1 (NF-1) and characterized by relatively irregular dome-shaped, plaque-like, or patchy boundaries. The present study examines the multimodal imaging characteristics of Yasunari nodules and their value in the diagnosis of NF-1. Materials and Methods: Medical records including optical coherence tomography (OCT), enhanced depth imaging OCT, infrared reflectance (IR) imaging, OCT angiography, and color fundus images of NF-1 patients who were examined at the Department of Ophthalmology in Dokuz Eylül University Faculty of Medicine between January 2022 and December 2023 were retrospectively reviewed for the presence of Yasunari nodules. Results: A total of 54 eyes of 27 patients were included in the study. At least one choroidal nodule was detected on IR imaging in 52 eyes (96.3%). In 31 (72.1%) of the 43 eyes (79.6%) with available high-quality OCT angiography images, choroidal nodules were observed as areas showing a flow deficit in the choriocapillaris layer. Of the total 54 eyes included, Lisch nodules without choroidal nodules were observed in 2 eyes (3.7%). In 16 eyes (29.6%), Lisch nodules were not detected despite the presence of choroidal nodules. Both Lisch nodules and choroidal nodules were detected in the other 36 eyes (66.7%). Conclusion: Yasunari nodules are frequently observed in NF-1 cases and can be easily detected with multimodal imaging techniques, especially IR imaging. The ability to visualize choroidal nodules before the appearance of Lisch nodules demonstrates the importance of Yasunari nodules in the diagnosis of NF-1.

NF1+/ex42del miniswine model the cellular disruptions and behavioral presentations of NF1-associated cognitive and motor impairment.

Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor-predisposition disorder. As many as 70% of children with NF1 report difficulties with spatial/working memory, attention, executive function, and fine motor movements. In contrast to the utilization of various Nf1 mouse models, here we employ an NF1+/ex42del miniswine model to evaluate the mechanisms and characteristics of these presentations, taking advantage of a large animal species more like human anatomy and physiology. The prefrontal lobe, anterior cingulate, and hippocampus from NF1+/ex42del and wild-type miniswine were examined longitudinally, revealing abnormalities in mature oligodendrocytes and astrocytes, and microglial activation over time. Imbalances in GABA: Glutamate ratios and GAD67 expression were observed in the hippocampus and motor cortex, supporting the role of disruption in inhibitory neurotransmission in NF1 cognitive impairment and motor dysfunction. Moreover, NF1+/ex42del miniswine demonstrated slower and shorter steps, indicative of a balance-preserving response commonly observed in NF1 patients, and progressive memory and learning impairments. Collectively, our findings affirm the effectiveness of NF1+/ex42del miniswine as a valuable resource for assessing cognitive and motor impairments associated with NF1, investigating the involvement of specific neural circuits and glia in these processes, and evaluating potential therapeutic interventions.

Dietary intervention rescues a bone porosity phenotype in a murine model of Neurofibromatosis Type 1 (NF1).

Neurofibromatosis type 1 (NF1) is a complex genetic disorder that affects a range of tissues including muscle and bone. Recent preclinical and clinical studies have shown that Nf1 deficiency in muscle causes metabolic changes resulting in intramyocellular lipid accumulation and muscle weakness. These can be subsequently rescued by dietary interventions aimed at modulating lipid availability and metabolism. It was speculated that the modified diet may rescue defects in cortical bone as NF1 deficiency has been reported to affect genes involved with lipid metabolism. Bone specimens were analyzed from wild type control mice as well as Nf1Prx1-/- (limb-targeted Nf1 knockout mice) fed standard chow versus a range of modified chows hypothesized to influence lipid metabolism. Mice were fed from 4 weeks to 12 weeks of age. MicroCT analysis was performed on the cortical bone to examine standard parameters (bone volume, tissue mineral density, cortical thickness) and specific porosity measures (closed pores corresponding to osteocyte lacunae, and larger open pores). Nf1Prx1-/- bones were found to have inferior bone properties to wild type bones, with a 4-fold increase in the porosity attributed to open pores. These measures were rescued by dietary interventions including a L-carnitine + medium-chain fatty acid supplemented chow previously shown to improve muscle histology function. Histological staining visualized these changes in bone porosity. These data support the concept that lipid metabolism may have a mechanistic impact on bone porosity and quality in NF1.

Identifying Lesions of the Corpus Callosum in Patients With Neurofibromatosis Type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a multisystemic autosomal dominant disorder that includes intracranial lesions such as unidentified bright objects (UBOs)-areas of increased T2 signal on magnetic resonance imaging (MRI)-and tumors known as gliomas. The presence of these lesions in the corpus callosum (CC) has not been previously studied in a large cohort. METHODS: We reviewed medical records of 681 patients (aged three months to 86 years) followed at our institution from 2000 to 2023 with NF1 and one or more brain MRI. Patients with lesions in the CC were identified, and RAPNO/RANO criteria were used to determine changes in size over time, where a change of 25% in the product of perpendicular measurements indicates growth or shrinkage. RESULTS: Forty-seven patients had CC UBOs, most of which were in the splenium (66.0%). Seventeen patients had CC gliomas (10% of those with any glioma), two of whom had two gliomas. Seventeen of 19 gliomas were in the splenium. Over follow-up, eight of 19 remained stable, three shrunk, and eight grew. The mean percentage change in the product of the dimensions was 311.5% (ranging from -46.7% to 2566.6%). Of the eight lesions that grew, one required treatment. CONCLUSIONS: There is a 6.9% and 2.5% prevalence of CC UBOs and gliomas, respectively, in our cohort of patients with NF1. Most lesions are present in the splenium, and although some gliomas demonstrate significant growth, they rarely require treatment. This work is the largest series of CC lesions in NF1 and adds to the growing data to inform appropriate follow-up.

Surgical Treatment Outcomes of Anterior-Only Correction and Reconstruction for Severe Cervical Kyphotic Deformity with Neurofibromatosis-1: A Retrospective Study with a 5-Year Follow-Up.

OBJECTIVES: Currently, anterior-only (AO), posterior-only, and combined anterior-posterior spinal fusions are common strategies for treating cervical kyphosis in patients with neurofibromatosis-1 NF-1. Nevertheless, the choice of surgical strategy remains a topic of controversy. The aim of our study is to evaluate the safety and effectiveness of anterior decompression and spinal reconstruction for the treatment of cervical kyphosis in patients with NF-1. METHODS: Twelve patients with NF-1-associated cervical kyphotic deformity were reviewed retrospectively between January 2010 and April 2020. All patients underwent AO correction and reconstruction. The X-ray was followed up in all these patients to assess the preoperative and postoperative local kyphosis angle (LKA), the global kyphosis angle (GKA), the sagittal vertical axis, and the T1 slope. The visual analog scale score, Japanese Orthopedic Association (JOA) score, and neck disability index (NDI) score were used to evaluate the improvement inclinical symptoms. The results of the difference in improvement from preoperatively to the final follow-up assessment were assessed using a paired t-test or Mann-Whitney U-test. RESULTS: The LKA and GKA decreased from the preoperative average of 64.42 (range, 38-86) and 35.50 (range, 10-81) to an average of 16.83 (range, -2 to 46) and 4.25 (range, -22 to 39) postoperatively, respectively. The average correction rates of the LKA and GKA were 76.11% and 111.97%, respectively. All patients had achieved satisfactory relief of neurological symptoms (p < 0.01). JOA scores were improved from 10.42 (range, 8-16) preoperatively to 15.25 (range, 11-18) at final follow-up (p < 0.01). NDI scores were decreased from an average of 23.25 (range, 16-34) preoperatively to an average of 7.08 (range, 3-15) at the final follow-up (p < 0.01). CONCLUSION: Anterior-only correction and reconstruction is a safe and effective method for correcting cervical kyphosis in NF-1 patients. In fixed cervical kyphosis cases, preoperative skull traction should also be considered.