BACKGROUND: Giant neurofibromas occurring in individuals diagnosed with neurofibromatosis type 1 (NF1) often result in considerable disfigurement, functional impairment, and diminished quality of life. Although debulking surgery poses inherent risks of complications, it remains the most efficacious approach to address these issues. The primary objective of this study was to share our surgical experience with giant neurofibromas in the extremities and trunk wall of NF1 patients which may help surgeons to minimize intraoperative bleeding and facilitate tumor excision.
METHODS: A retrospective review was conducted at a single center, encompassing 36 NF1 patients with giant neurofibromas in the extremities and trunk wall who underwent debulking surgery from July 2010 to July 2022.
RESULTS: Twenty-one male and fifteen female NF1 patients who received one to four surgical interventions were evaluated. The average age at the time of surgery was 17.8 years. The median follow-up time was 52 months. Our findings revealed relatively low rates of complications and recurrence. Notably, patients expressed satisfaction with both the aesthetic and functional results.
CONCLUSIONS: Debulking surgery of giant neurofibromas in the extremities and trunk wall of NF1 patients can effectively reduce the tumor burden, leading to improvements in both the appearance and function.

BACKGROUND: Neurofibromatosis type 1 (NF 1) is an autosomal-dominant tumor predisposition genetic disease affecting approximately 1 in 3000 live births. The condition could present various manifestations ranging from skin abnormalities to neurological tumors. The musculoskeletal system could also be frequently affected, and scoliosis is the most common orthopedic manifestation. Characterized by the early-onset and rapid progression tendency, NF 1-related dystrophic scoliosis presented discrepancies from idiopathic scoliosis in terms of natural history, clinical features, and management outcomes and thus required special attention. In the current study, the authors conducted a systemic review to outline the body of evidence of the natural history, clinical characteristics, surgical outcomes, and surgical complications of NF 1-induced scoliosis, aiming to provide an elucidative insight into this condition.
METHODS: Systemic review and meta-analysis were conducted according to the latest Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) guidelines. The search was performed in Medline, Embase, and Web of Science Core Collection up to December 27, 2022, using related keywords. Clinical features such as frequencies, segmental involvement, and hereditary information were summarized and described qualitatively. Meta-analysis was conducted using R software and the \'meta\' package to yield an overall outcome of efficacy and safety of surgical management, precisely, spinal fusion procedure and growing rods procedure. Corrective rate of Cobb angle, sagittal kyphosis angle, and T1-S1 length post-operative and at the last follow-up was used to evaluate the efficacy, and the occurrence of surgery-related complications was used to evaluate the safety.
RESULTS: A total of 37 articles involving 1023 patients were included. Approximately 26.6% of the NF 1 patients would present with scoliosis. Patients tend to develop scoliosis at an earlier age. The thoracic part turned out to be the most affected segment. No obvious correlation between scoliosis and genotype or hereditary type was observed. Both spinal fusion and growing rod surgery have shown acceptable treatment outcomes, with spinal fusion demonstrating better performance in terms of effectiveness and safety. The growing rods technique seemed to allow a better lengthening of the spine. The mainstay post-operative complications were implant-related complications but could be managed with limited revision surgery. Severe neurological deficits were rarely reported.
CONCLUSIONS: Scoliosis, especially the subtype characterized by dystrophic bony changes, is a significant orthopedic manifestation of NF1. It has an early onset, a tendency to persistently and rapidly progress, and is challenging to deal with. The current review outlines the available evidence from the perspective of natural history, clinical features, and the treatment efficacy and safety of the mainstay surgical options. Patients with NF1 scoliosis will benefit from a better understanding of the disease and evidence based treatment strategies.

UNASSIGNED: To summarize the gene therapy strategies for neurofibromatosis type 1 (NF1) and related research progress.
UNASSIGNED: The recent literature on gene therapy for NF1 at home and abroad was reviewed. The structure and function of the NF1 gene and its mutations were analyzed, and the current status as well as future prospects of the transgenic therapy and gene editing strategies were summarized.
UNASSIGNED: NF1 is an autosomal dominantly inherited tumor predisposition syndrome caused by mutations in the NF1 tumor suppressor gene, which impair the function of the neurofibromin and lead to the disease. It has complex clinical manifestations and is not yet curable. Gene therapy strategies for NF1 are still in the research and development stage. Existing studies on the transgenic therapy for NF1 have mainly focused on the construction and expression of the GTPase-activating protein-related domain in cells that lack of functional neurofibromin, confirming the feasibility of the transgenic therapy for NF1. Future research may focus on split adeno-associated virus (AAV) gene delivery, oversized AAV gene delivery, and the development of new vectors for targeted delivery of full-length NF1 cDNA. In addition, the gene editing tools of the new generation have great potential to treat monogenic genetic diseases such as NF1, but need to be further validated in terms of efficiency and safety.
UNASSIGNED: Gene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.
UNASSIGNED: 总结Ⅰ型神经纤维瘤病（neurofibromatosis type 1，NF1）基因治疗策略和相关研究进展。.
UNASSIGNED: 查阅近年来国内外关于NF1基因治疗的文献，对NF1基因结构、功能及其突变进行分析，并从转基因治疗和基因编辑两方面对基因治疗策略进行深入总结。.
UNASSIGNED: NF1是由抑癌基因NF1基因突变引起的常染色体显性遗传肿瘤性疾病，因神经纤维瘤蛋白功能受损而致病，临床表现复杂，目前尚无法根治。NF1的基因治疗策略仍处于研究和开发阶段。现有NF1转基因疗法主要是在神经纤维瘤蛋白缺陷的细胞中构建并表达Ras-GTP酶激活蛋白相关结构域基因片段，证实了NF1基因治疗的可行性；未来研究方向主要聚焦于使用拆分载体递送系统，增加单一载体的运载量，以及开发新的递送系统用于靶向递送全长NF1 cDNA。此外，新一代基因编辑工具在NF1等单基因遗传病的治疗领域应用潜力巨大，但效率和安全性尚需进一步验证。.
UNASSIGNED: 基因治疗，包括转基因和基因编辑两大技术，有望成为NF1患者重要的新型治疗手段。.

A newborn with giant faciocervical mass and presented with asphyxia during birth was admitted to the hospital. After stabilizing her vital sign, we provided the patient with image examinations and whole-exome sequencing, which revealed a heterozygous variation of neurofibromatosis type 1 (NF1). The final diagnosis of the patient was NF1 complicated with neonatal hypoxic-ischemic encephalopathy (NHIE). During hospitalization, the patient received comprehensive and systematic care. There was no reports of similar cases in the literature. So, this report aimed to elucidate the special clinical manifestations, diagnosis, treatment and prognosis of NF1 complicated with NHIE by analyzing the clinical data of the patient and her family and reviewing relevant literature.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a highly heterogeneous autosomal genetic disorder characterized by a broad spectrum of clinical and molecular manifestations. The correlations between genotype and phenotype in NF1 remain elusive. This study aimed to elucidate genotype-phenotype associations in a large Chinese cohort of NF1 patients.
METHODS: We included NF1 patients from our center who underwent genetic testing for NF1 variants and systemic examination. Genotype-phenotype correlation analyses were performed, focusing on variation types and involved neurofibromin domains.
RESULTS: A total of 195 patients were enrolled, comprising 105 males and 90 females, with a median age of 18 years. Truncating variants, single amino acid variations, and splicing variants accounted for 139/195 (71.3%), 23/195 (11.8%), and 33/195 (16.9%), respectively. Patients with splicing variants exhibited a significantly higher prevalence of spinal plexiform neurofibromas (spinal PNF) than those with truncating variants (76.4% vs. 51.8%; p = 0.022). Variations affecting the PKC domain were associated with higher rates of cutaneous neurofibromas (CNF) (100% vs. 64.9%, p < 0.001), Lisch nodules (100% vs. 61.2%, p < 0.001), plexiform neurofibromas (PNF) (100% vs. 95.7%, p = 0.009), and psychiatric disorders (11.8% vs. 1.6%, p = 0.042). Patients with mutations in the CSRD had an elevated risk of secondary primary malignancies (11.6% vs. 2.8%, p = 0.015). GRD involvement might enhance the risk of Lisch nodules (76.9% vs. 53.7%, p = 0.044). Variations in the Sec14-PH domain were correlated with a higher rate of CNF (76.8% vs. 58.6%, p = 0.014). Additionally, we found that the p.R1748* variants carry a high risk of malignancy.
CONCLUSIONS: Our study suggested some novel genotype-phenotype correlations within a Chinese cohort, providing innovative insights into this complex field that may contribute to genetic counseling, risk stratification, and clinical management for the NF1 population.

Neurofibromatosis type 1 (NF1) is a genetic disorder involving multiple organs. Vascular involvement is a rare complication among NF1 patients. We report a case of a 59-year-old female NF1 patient who presented with a massive hematoma over the scapular area after undergoing acupuncture treatment. Contrast-enhanced CT and MRI demonstrated a slightly hyperdense mass measuring 24.2 × 10.3 cm in size, and multiple enlarged and tortuous malformed vessels were seen arising from the left subclavian artery. Arterial embolization and subsequent surgical mass resection were successfully performed. This case indicates that minor injuries such as acupuncture-related ones could cause severe hemorrhage in patients with vascular malformation related to NF1. Endovascular angiography and embolization proved to be effective in localizing the culprit vessel and stopping active bleeding in our patient.

Multiple gastrointestinal stromal tumors (GISTs) combined with cutaneous multiple neurofibromas are clinically rare. This paper presents a case of multiple gastrointestinal stromal tumors in the jejunum of a 68-year-old mother, along with her daughter who also had coexisting cutaneous multiple neurofibromas. The mother had been experiencing repeated melena for over 2 years and had previously been diagnosed with multiple small intestinal masses at other hospitals. Additionally, her 42-year-old daughter was admitted to our department due to recurrent abdominal pain caused by cholecystolithiasis. The mother and daughter both exhibited multiple nodular masses of varying sizes on their skin, including the truncus, limbs, and face, which were diagnosed as neurofibromas. The mother underwent a partial excision of the jejunum and a lateral jejunojejunal anastomosis side-to-side, as well as excision of skin lesions in our department. The final diagnosis of wild-type GISTs associated with neurofibromatosis type 1 (NF1) was confirmed through postoperative pathology, immunohistochemistry, and genetic testing results. During preoperative gastrointestinal endoscopy and intraoperative laparoscopic exploration of the gastrointestinal tract, no obvious tumors were found in her daughter. A combination of patient observations and a review of relevant literature in the field suggests that when patients present with gastrointestinal symptoms and multiple irregular painless swellings in the skin, it is important to consider the possibility of an association with NF1 and GIST. Additionally, obtaining a detailed family history can save time and improve the diagnosis of patients with both NF1 and GIST. We recommend that even if there are no gastrointestinal manifestations of GISTs in the offspring of newly mutated NF1 patients, regular review of gastroenteroscopy, imaging examination, and long-term follow-up after middle age are still crucial for the early diagnosis and treatment of NF1-related GISTs.

UNASSIGNED: Given the considerable discrepancies in the evidence concerning the efficacy of statins in ameliorating cognitive impairments in pediatric patients with Neurofibromatosis Type 1 (NF-1), this study conducts a systematic review and meta-analysis to consolidate existing evidence to evaluate the efficacy of statins on cognitive impairments in children with NF-1.
UNASSIGNED: This study adhered to the PRISMA statement, and the research protocol was pre-registered on PROSPERO (#CRD: 42022369072). Comprehensive searches of databases including PubMed, Embase, and the Cochrane Library were performed up to March 31, 2023 to identify randomized controlled trials (RCTs) investigating the effects of statins on cognitive impairments in children with NF-1. Statistical analyses were conducted using Review Manager 5.4.1. A fixed- or random-effects model was employed according to the I2 statistic. As all data were continuous, MD [95% CI] was used as the pooled estimate.
UNASSIGNED: The final analysis included five RCTs with a total of 364 patients. The meta-analysis indicated that aside from a statistically significant improvement in internalizing problems (MD [95%CI] = 3.61[0.11, 7.10], p = 0.04), Object assembly Test (MD [95%CI] = 0.53[0.12, 0.93], p = 0.01), Cancellation Test (MD [95%CI] = 3.61[0.11, 7.10], p < 0.0001), statins did not exhibit significant efficacy in improving other cognitive aspects in children with NF-1 (p > 0.05). An additional descriptive analysis on indices that cannot be meta-analyzed revealed considerable inconsistency in the therapeutic effect of statins across different studies.
UNASSIGNED: Current evidence suggests that statins may not be effective for cognitive performance in children with NF-1.

BACKGROUND: A pseudoaneurysm of the superficial temporal artery is an uncommon clinical entity that has largely been linked with direct traumatic causes. Neurofibromatosis type 1 (NF1)-related vasculopathy is a rare cause of idiopathic arterial bleeding in the craniofacial region.
METHODS: A 46-year-old male with clinical features of NF1 presented to the hospital with an enlarging and tender right temporal mass without a history of trauma. Computed tomography angiography suggested the development of a pseudoaneurysm, and surgery was performed to resect the mass. Histopathological examinations showed focal interruption of the epithelium layer and elastic lamina, well-demarcated thickening of the smooth muscle layers of the arterial wall, supporting the diagnosis of pseudoaneurysm.
CONCLUSIONS: NF1-associated vasculopathy is likely the predisposing factor for the development of a superficial temporal artery pseudoaneurysm.

BACKGROUND: Neurofibromatosis type 1 (NF-1) is caused by mutations in the NF1 gene that encodes neurofibromin, a negative regulator of RAS proto-oncogene. Approximately one-third of the reported pathogenic mutations in NF1 are splicing mutations, but most consequences are unclear. The objective of this study was to identify the pathogenicity of splicing mutation in a Chinese family with NF-1 and determine the effects of the pre-mRNA splicing mutation by in vitro functional analysis.
METHODS: Next-generation sequencing was used to screen candidate mutations. We performed a minigene splicing assay to determine the effect of the splicing mutation on NF1 expression, and three-dimensional structure models of neurofibromin were generated using SWISS-MODEL and PROCHECK methods, respectively.
RESULTS: A pathogenic splicing mutation c.479+1G>C in NF1 was found in the proband characterized by childhood-onset refractory hypertension. In vitro analysis demonstrated that c.479+1G>C mutation caused the skipping of exon 4, leading to a glutamine-to-valine substitution at position 97 in neurofibromin and an open reading frame shift terminating at codon 108. Protein modeling showed that several major domains were missing in the truncated neurofibromin protein.
CONCLUSIONS: The splicing mutation c.479+1G>C identified in a Chinese patient with NF-1 and childhood-onset refractory hypertension caused the skipping of exon 4 and a truncated protein. Our findings offer new evidence for the molecular diagnosis of NF-1.