OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

OBJECTIVE: To summarize the gene therapy strategies for neurofibromatosis type 1 (NF1) and related research progress. METHODS: 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. RESULTS: 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. CONCLUSION Gene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.
Humans ; Neurofibromatosis 1/pathology* ; Neurofibromin 1/metabolism* ; GTPase-Activating Proteins ; Mutation ; Genetic Predisposition to Disease ; Genetic Therapy

Humans ; Neurofibromatosis 1/pathology*

Management of large-size retrorectal gastrointestinal stromal tumors (GISTs) is complex and challenging from diagnosis to treatment. This may create technical difficulties in surgical access and complete resection of the tumor. The abdominosacral resection has the benefit of improved visualization via the anterior incision, with enhanced exposure of the midrectal area, which makes resecting the tumor completely via the posterior approach easier. We report 2 cases of patients with a retrorectal GIST and neurofibromatosis type 1, one in a 27-year-old woman with a defecation complaint and the other in a 58-year-old woman with a defecation and urination complaint. Based on the anatomical pathology, both patients were diagnosed with a GIST. The tumors were excised via an abdominosacral resection. Retrorectal GISTs are rare, and abdominosacral resection allows complete resection of a large-size retrorectal GIST with low morbidity and an absence of functional impairment. The abdominosacral resection should be considered in certain situations.
Adult ; Defecation ; Diagnosis ; Disease Management ; Female ; Gastrointestinal Stromal Tumors ; Humans ; Middle Aged ; Neurofibromatosis 1 ; Pathology ; Rectal Neoplasms ; Urination

PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of sarcoma that occur spontaneously or in association with neurofibromatosis type 1 (NF-1). This study aimed to clinically differentiate these types of MPNSTs. MATERIALS AND METHODS: The study reviewed 95 patients diagnosed with and treated for MPNST at Yonsei University Health System, Seoul, Korea over a 27-year period. The clinical characteristics, prognostic factors, and treatment outcomes of sporadic MPNST (sMPNST) and NF-1 associated MPNST (NF-MPNST) cases were compared. RESULTS: Patients with NF-MPNST had a significantly lower median age (32 years vs. 45 years for sMPNST, p=0.012), significantly larger median tumor size (8.2 cm vs. 5.0 cm for sMPNST, p < 0.001), and significantly larger numbers of imaging studies and surgeries (p=0.004 and p < 0.001, respectively). The 10-year overall survival (OS) rate of the patients with MPNST was 52±6%. Among the patients with localized MPNST, patients with NF-MPNST had a significantly lower 10-year OS rate (45±11% vs. 60±8% for sMPNST, p=0.046). Univariate analysis revealed the resection margin, pathology grade, and metastasis to be significant factors affecting the OS (p=0.001, p=0.020, and p < 0.001, respectively). Multivariate analysis of the patients with localized MPNST identified R2 resection and G1 as significant prognostic factors for OS. CONCLUSION: NF-MPNST has different clinical features from sMPNST and requires more careful management. Further study will be needed to develop specific management plans for NF-MPNST.
Humans ; Korea ; Multivariate Analysis ; Neoplasm Metastasis ; Neurilemmoma* ; Neurofibromatoses* ; Neurofibromatosis 1* ; Pathology ; Sarcoma ; Seoul

Adolescent ; Brain ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Neurofibromatosis 1 ; pathology

OBJECTIVETo investigate the surgical mode, recurrence and prognosis for patients with head and neck neurofibromas and explore their treatment strategies.

METHODSThe clinicopathological features, operation mode, prognosis and neural function of 46 patients with head and neck neurofibroma were analyzed retrospectively, and 41 of the cases were followed up for 24-170 months (median 74 months).

RESULTSAmong the 41 followed-up patients, 26 patients were cured and 15 patients were not cured (two died). The cure rate of the neurofibromas with neurofibromatosis type 1 (NF1) and the neurofibromas without NF1 were 42.9% and 85.0%, respectively (P = 0.005). The cure rate of localized, aggressive, diffuse and beaded neurofibromas were 100.0%, 46.6%, 40.0% and 66.7%, respectively (P = 0.009). The cure rate of radical resection (including expanding excision and complete resection) and partial resection were 73.5% and 14.3%, respectively (P = 0.011). The cure rates of expanding excision and partial resection were 80.0% and 14.3% (P = 0.029). The cure rates of complete resection and partial resection were 70.8% and 14.3%, respectively (P = 0.026). However, the cure rates of expanding excision and complete resection were not significantly different (P = 0.581). Multivariate Cox model analysis indicated that thoroughness of surgery was the independent risk factor for the prognosis for patients with head and neck neurofibromas.

CONCLUSIONSNeurofibroma is a kind of aggressive benign tumors. Some neurofibromas have a high recurrence rate and low recovery rate, and some nerves are essay to be injured in the operation. Lots of factors impact on the prognosis and recovery of the neural function. Therefore, operation opportunity and mode should be carefully selected.

Follow-Up Studies ; Head and Neck Neoplasms ; pathology ; surgery ; Humans ; Neoplasm Recurrence, Local ; Neurofibroma ; pathology ; surgery ; Neurofibromatosis 1 ; pathology ; surgery ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Time Factors

No abstract available.
Endoscopy, Digestive System ; Gastrointestinal Hemorrhage/*etiology ; Gastrointestinal Stromal Tumors/complications/*diagnosis/radionuclide imaging ; Humans ; Jejunum/pathology ; Male ; Middle Aged ; Neurofibromatosis 1/complications/*diagnosis/pathology ; Proto-Oncogene Proteins c-kit/metabolism ; Tomography, X-Ray Computed

Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited familial tumor syndrome. Benign tumors such as pilocytic astrocytoma, optic glioma make up the majority of intracranial neoplasms in patients with NF1. There have only been a handful of cases in which adult glioblastoma presented with NF1. A 32-year-old male presented with headache and radiological studies showing a high grade intra-axial tumor. The patient underwent gross total surgical excision and the pathology revealed glioblastoma. After the surgery, he received concomitant chemo-radiotherapy with temozolomide and adjuvant temozolomide chemotherapy. We report a NF1 patient who developed glioblastoma and reviewed related articles.
Adult ; Astrocytoma ; Brain Neoplasms ; Drug Therapy ; Glioblastoma* ; Hand ; Headache ; Humans ; Male ; Neurofibromatosis 1* ; Optic Nerve Glioma ; Pathology

Type 1 neurofibromatosis (von Recklinghausen's disease, NF-1) is an autosomal-dominant neurocutaneous-disorder characterized by systemic cafe'-au-lait spots, multiple cutaneous neurofibromas, axillary or inguinal freckling, and Lisch nodules (pigmented iris hamartomas). Approximately 10-25% of NF1 patients have gastrointestinal neoplasms. Gastrointestinal stromal tumor (GIST) in patients with neurofibromatosis is most commonly found in the small bowel and the stomach, and approximately 60% of such patients have multiple tumors or multiple tumor sites. Although, the increased incidence of GIST in patients with neurofibromatosis is well documented in pathology literature in English, but has rarely been documented in Korea. Here, we report a case of multiple GISTs in a 48-year-old woman accompanied by NF1. She was admitted to Yeungnam University Hospital with complaints of melena and dyspnea. A contrast-enhanced computed tomography (CT) scan revealed that multiple soft tissue masses were occupying the entire peritoneal cavity. An ultrasonogram- guided biopsy was performed and the tumors were found to have been composed of tumor cells that were positive for c-kit protein. The patient was put on Imatinib mesylate treatment, and further follow-up will be carried out.
Biopsy ; Dyspnea ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors* ; Humans ; Incidence ; Iris ; Korea ; Melena ; Mesylates ; Middle Aged ; Neurofibroma ; Neurofibromatoses ; Neurofibromatosis 1* ; Pathology ; Peritoneal Cavity ; Proto-Oncogene Proteins c-kit ; Stomach ; Imatinib Mesylate