Su Song, Bai Yuexia, Lu Yi, Ren Ying, Zhang Wenchao, Wang Guangyu, Ma Kai, Zhang Hongwei
Department of Neurology, Children's Hospital Affiliated to Shandong University, Jinan, Shandong, China.
Department of Neurology, Jinan Children's Hospital, Jinan, Shandong, China.
Int J Dev Neurosci. 2025 Oct;85(6):e70049. doi: 10.1002/jdn.70049.
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, with plexiform neurofibromas occurring in approximately 20%-50% of patients. A 12-year-old girl underwent surgery due to unbearable pain caused by diffuse neurofibromas. Postoperatively, the girl exhibited rapid growth and extremely extensive plexiform neurofibromas, with multiple plexiform neurofibromas that were inoperable. Through high-throughput sequencing (HTS), genetic molecular analysis was conducted on the peripheral blood samples of the child, and it was found that there was a splice site mutation c.3113 + 1G > A in the NF1 gene. Additionally, we identified a pathogenic variant c.2033dup (Ile679Aspfs*21), citing ClinVar and PMID: 77655472 to confirm its established pathogenicity in the paraffin-embedded section sample of the diffuse neurofibroma, which was exclusively found in the girl's plexiform neurofibroma. This 'second-hit' mutation could explain the rapid growth of the diffuse neurofibroma. The patient was effectively treated with oral administration of the selective MEK inhibitor selumetinib, resulting in rapid tumour regression. The treatment has shown promising efficacy against the rapid tumour growth induced by the patient's 'second-hit' mutation.
1型神经纤维瘤病（NF1）是一种常染色体显性遗传病，约20%-50%的患者会出现丛状神经纤维瘤。一名12岁女孩因弥漫性神经纤维瘤引起的难以忍受的疼痛接受了手术。术后，该女孩的丛状神经纤维瘤生长迅速且范围极广，多个丛状神经纤维瘤无法手术切除。通过高通量测序（HTS）对该患儿的外周血样本进行基因分子分析，发现NF1基因存在剪接位点突变c.3113 + 1G > A。此外，我们在弥漫性神经纤维瘤的石蜡包埋切片样本中鉴定出一个致病变异c.2033dup（Ile679Aspfs*21），引用ClinVar和PMID: 77655472来确认其已确定的致病性，该变异仅在该女孩的丛状神经纤维瘤中发现。这种“二次打击”突变可以解释弥漫性神经纤维瘤的快速生长。该患者口服选择性MEK抑制剂司美替尼后得到有效治疗，肿瘤迅速消退。该治疗方法对由患者“二次打击”突变引起的肿瘤快速生长显示出有前景的疗效。
