背景:1型神经纤维瘤病(NF1)是一种常染色体显性遗传的癌症易感性综合征,由NF1中的致病性变体引起,其负调节RAS途径。了解该疾病的基因型-表型相关性是预后评估和早期发现恶性周围神经鞘瘤(MPNST)的重要工具,这些患者中约有10%存在。我们介绍了一名青少年的病例,该青少年患有左下颌MPNST和NF1上以前未报告的种系致病变异。
方法:一名11岁临床诊断为NF1的女性患者因晚期MPNST转诊至我院。获得了以前未报告的NF1致病性变体(GRCh37:NM_182493.2c.3299C>G,p.Ser1100*)。尽管外科和医疗团队付出了巨大的努力,肿瘤进展无法停止,导致病人死亡。
结论:由于MPNSTs对目前的治疗方案难以治疗,早期诊断,以及新疗法的发展,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:在患有1型母系遗传性神经纤维瘤病和MPNST的患者中,一种新的NF1致病变异的报告增加了对该疾病基因型-表型相关性的认识。
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.
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.
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.
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.