Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Int J Mol Sci. 2019 Jun 10;20(11):2819. doi: 10.3390/ijms20112819.
A syndrome of multiple paragangliomas/pheochromocytomas, somatostatinoma, and polycythemia due to somatic mosaic gain-of-function mutation of , encoding HIF-2α, was previously described. HIF-2α has been implicated in endochondral and intramembranous ossification. Abnormal bone growth of the skull base may lead to Chiari malformation type I. We report two cases of gain-of-function mutation syndrome with Chiari malformation and developmental skull base anomalies. Patients were referred to the Section on Medical Endocrinology, NICHD, NIH for evaluation of recurrent and metastatic paragangliomas or pheochromocytoma. The syndrome was confirmed genetically by identification of the functional gain-of-function mutation in the resected tumors and circulating leukocytes. Both patients were confirmed for characteristics of gain-of-function mutation syndrome by complete blood count (CBC), plasma biochemistry, and computed tomography (CT) of the abdomen and pelvis. Chiari malformation type I and abnormal bony development of the posterior fossa was found on MRI and CT of the head. The present study implicates mutations in abnormal posterior fossa development resulting in Chiari malformation type I.
先前描述了一种由于编码 HIF-2α 的体细胞获得性功能突变导致的多发性副神经节瘤/嗜铬细胞瘤、生长抑素瘤和红细胞增多症综合征。HIF-2α 与软骨内和膜内成骨有关。颅底骨骼生长异常可能导致 Chiari 畸形 I 型。我们报告了两例具有 Chiari 畸形和颅底发育异常的获得性功能突变综合征病例。患者被转介到 NICHD 医学内分泌科，接受复发性和转移性副神经节瘤或嗜铬细胞瘤的评估。通过鉴定切除肿瘤和循环白细胞中的功能性获得性功能突变，从遗传学上确认了该综合征。通过全血细胞计数（CBC）、血浆生化和腹部及骨盆计算机断层扫描（CT），对两名患者进行了获得性功能突变综合征的特征确认。头部 MRI 和 CT 显示 Chiari 畸形 I 型和后颅窝异常骨发育。本研究提示 突变导致异常后颅窝发育，从而导致 Chiari 畸形 I 型。
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