Nguyen Anthony V, Berger Blaine H, Abdullaev Zied, Gearhart Samuel, Castro-Echeverry Eduardo, Aldape Kenneth, Trumble Eric, Lehman Norman L
Department of Neurosurgery, Baylor Scott and White Medical Center, Baylor College of Medicine, Temple, TX, USA.
Department of Pathology and Laboratory Medicine, Baylor Scott and White Medical Center, Baylor College of Medicine, Temple, TX, USA.
Mol Biol Rep. 2025 Jan 10;52(1):112. doi: 10.1007/s11033-024-10201-8.
Brain intraparenchymal schwannoma is a rare clinical entity, generally curable with adequate resection.
We describe a case in a male patient first presenting at 19 months of age, the youngest reported age for this lesion. It also appears to be the first case connected to a germline TSC2 p.1510del mutation in a patient with autism-like symptoms. Although tuberous sclerosis is generally not associated with increased risk of schwannoma, mTORC1 activity, which is inhibited by intact TSC1/TSC2 complex, is involved in schwannoma progression. This patient's tumor also harbored a CHD7::VGLL3 fusion consistent with its genomic DNA methylation classification of CNS Schwannoma, VGLL-fused. The Hippo pathway, mTORC1, and VGLL3 all negatively regulate the YAP1/TEAD cotranscriptional complex. We hypothesize that this schwannoma may have arisen because of increased VGLL3 functional activity from the CHD7::VGLL3 fusion and, perhaps, increased mTORC1 activity due to TSC2 mutation, and their combined effects on the balance between YAP1/TEAD- and VGLL3/TEAD-mediated transcriptional programs.
We present a frontal lobe intra-axial parenchymal schwannoma containing a CHD7::VGLL3 gene fusion presenting in a 19 month-old male, the youngest patient yet reported for this lesion.
脑实质内神经鞘瘤是一种罕见的临床实体，通常通过充分切除可治愈。
我们描述了一例男性患者，首次发病于19个月大，这是该病变报道的最小年龄。这似乎也是首例与患有自闭症样症状患者的种系TSC2 p.1510del突变相关的病例。虽然结节性硬化症一般与神经鞘瘤风险增加无关，但完整的TSC1/TSC2复合物所抑制的mTORC1活性参与神经鞘瘤进展。该患者的肿瘤还存在CHD7::VGLL3融合，与其CNS神经鞘瘤、VGLL融合的基因组DNA甲基化分类一致。Hippo通路、mTORC1和VGLL3均对YAP1/TEAD共转录复合物起负调节作用。我们推测，该神经鞘瘤可能是由于CHD7::VGLL3融合导致VGLL3功能活性增加，或许还由于TSC2突变导致mTORC1活性增加，以及它们对YAP1/TEAD和VGLL3/TEAD介导的转录程序之间平衡的联合作用而产生。
我们报告了一例19个月大男性患者的额叶轴内实质神经鞘瘤，其中含有CHD7::VGLL3基因融合，这是该病变报道的最年轻患者。
