Introduction

Neurofibromatosis type 1 (NF1) is an autosomal dominant cancer predisposition syndrome caused by pathogenic variants in NF1, which negatively regulates the RAS pathway. Knowledge of the genotype-phenotype correlation in this disease is an important tool for prognostic evaluation and early detection of malignant peripheral nerve sheath tumors (MPNST), present in approximately 10% of these patients. We present the case of a teenager with a left jaw MPNST and a previously unreported germline pathogenic variant on NF1.

Case Presentation

An 11-year-old female with a NF1 clinical diagnosis was referred to our hospital with a MPNST in an advanced state. A previously unreported NF1 pathogenic variant was obtained (GRCh37: NM_182493.2 c.3299C>G, p.Ser1100*). Despite great efforts from the surgical and medical teams, the tumor progression couldn't be halted, resulting in the patient's death.

Discussion

As MPNSTs are refractory to current treatment regimens, early diagnosis, and development of new therapies, such as MEK inhibitors, is necessary for reducing morbidity and mortality within NF1 patients. This increases the importance of a more widespread genetic testing strategy.

Conclusion

The report of a novel NF1 pathogenic variant in a patient with maternally inherited neurofibromatosis type 1 and a MPNST increases the knowledge of the genotype-phenotype correlation in the disease.

中文翻译：

---

母系遗传的新型 NF1 基因致病性种系变异患者的恶性周围神经鞘瘤：病例报告

介绍

1 型神经纤维瘤病(NF1) 是一种常染色体显性遗传癌症易感综合征，由NF1中的致病变异引起，它负向调节 RAS 通路。了解这种疾病的基因型-表型相关性是恶性周围神经鞘瘤 (MPNST) 的预后评估和早期检测的重要工具，这些患者中约有 10% 存在这种肿瘤。我们介绍了一名患有左颌 MPNST 和先前未报告的NF1胚系致病性变异的青少年病例。

案例展示

一名临床诊断为 NF1 的 11 岁女性因晚期 MPNST 被转诊至我们医院。获得了以前未报告的NF1致病性变异 (GRCh37: NM_182493.2 c.3299C>G, p.Ser1100*)。尽管外科和医疗团队付出了巨大努力，但仍无法阻止肿瘤的发展，最终导致患者死亡。

讨论

由于 MPNSTs 对当前的治疗方案难以治疗，因此早期诊断和开发新疗法（如 MEK 抑制剂）对于降低 NF1 患者的发病率和死亡率是必要的。这增加了更广泛的基因检测策略的重要性。

结论

母系遗传 1 型神经纤维瘤病和 MPNST 患者的新型 NF1 致病性变异的报告增加了对该疾病的基因型-表型相关性的认识。