Ishii Kazuhiro, Tozaka Naoki, Tsutsumi Satoshi, Muroi Ai, Tamaoka Akira
Department of Neurology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennnoudai, Tsukuba, Ibaraki, 305-8575.
Department of Neurological Surgery, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021.
Medicine (Baltimore). 2020 Jul 17;99(29):e19800. doi: 10.1097/MD.0000000000019800.
Cerebral cavernous malformation (CCM) of the familial type is caused by abnormalities in the CCM1, CCM2, and CCM3 genes. These 3 proteins forming a complex associate with the maintenance of vascular endothelial cell-cell junctions. Dysfunction of these proteins results in the development of hemangiomas and abnormal intercellular junctions.
We report a 68-year-old man with familial cerebral cavernous malformation with initial presentation as convulsions at an advanced age. Brain magnetic resonance imaging revealed multiple cavernous hemangiomas in the right occipital lobe. The convulsions were considered to be induced by hemorrhage from cavernous hemangioma in the right occipital lobe.
Genetic screening of the CCM1, CCM2, and CCM3 genes revealed a novel mutation in the CCM2 gene (exon4 c: 359 T>A, p: V120D). No abnormalities were found in CCM1 or CCM3. Therefore, we diagnosed the patient with familial CCM caused by a CCM2 mutation.
This patient was treated with the administration of levetiracetam at a dosage of 1000 mg/day.
No seizures have been observed since the antiepileptic drug was administered. We performed brain magnetic resonance imaging (MRI) regularly to follow-up on appearance of new cerebral hemorrhages and cavernous hemangiomas.
This report reviews cases of familial cerebral cavernous malformations caused by abnormalities in the CCM2 gene. This mutation site mediates interactions with CCM1 and CCM3. The mutation occurs in the phosphotyrosine binding (PTB) site, which is considered functionally important to CCM2.
家族性脑海绵状畸形（CCM）由CCM1、CCM2和CCM3基因异常引起。这三种蛋白质形成一个复合物，与维持血管内皮细胞间连接有关。这些蛋白质功能异常会导致血管瘤的形成和细胞间连接异常。
我们报告一名68岁患有家族性脑海绵状畸形的男性，其初发症状为高龄时出现惊厥。脑部磁共振成像显示右枕叶有多个海绵状血管瘤。惊厥被认为是由右枕叶海绵状血管瘤出血诱发的。
对CCM1、CCM2和CCM3基因进行基因筛查，发现CCM2基因有一个新突变（外显子4 c：359 T>A，p：V120D）。CCM1和CCM3未发现异常。因此，我们诊断该患者为CCM2突变导致的家族性CCM。
该患者接受了左乙拉西坦治疗，剂量为1000毫克/天。
自服用抗癫痫药物以来未观察到癫痫发作。我们定期进行脑部磁共振成像（MRI）以随访新的脑出血和海绵状血管瘤的出现情况。
本报告回顾了由CCM2基因异常引起的家族性脑海绵状畸形病例。该突变位点介导与CCM1和CCM3的相互作用。该突变发生在磷酸酪氨酸结合（PTB）位点，这被认为对CCM2具有重要功能意义。
