伴高血压及脑出血的常染色体显性遗传脑动脉病伴皮质下梗死和白质脑病合并NOTCH3基因新突变的临床特点分析(附1家系报告)

Analysis of clinical characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy with hypertension and cerebral hemorrhage combined with a new NOTCH3 gene mutation(report of one family)

目的探讨伴高血压及脑出血的常染色体显性遗传脑动脉病伴皮质下梗死和白质脑病(CADASIL)合并NOTCH3基因位点新突变的临床特点。方法回顾性分析2021年8月就诊于山东大学齐鲁医院神经内科1例CADASIL患者的病例资料、家系情况及致病基因,并检索国内外相关文献进行探讨。结果先证者以反复发生脑出血、进行性记忆力和计算力下降及认知功能障碍为主要临床表现,家系调查发现该家系4代10人中4人有轻重不等的CADASIL症状。先证者头颅MRI+MRA+SWI示右侧枕叶及邻近胼胝体亚急性血肿、脑内多发出血灶、脑白质高信号、左侧脑室增大,基因检测提示NOTCH3基因存在一处杂合变异(c.517dupAchr19:15302932p.T173Nfs*23)。结论CADASIL不仅可表现为缺血性脑卒中,而且可合并高血压及脑出血。根据临床表现、影像学检查和基因检测结果,先证者符合CADASIL的诊断,该家系携带的NOTCH3基因的突变位点c.517dupAchr19:15302932p.T173Nfs*23可能为其家系发病的病因。

Objective To investigate the clinical characteristics of autosomal dominant cerebral artery disease with subcortical infarction and white matter encephalopathy(CADASIL)with new mutations of NOTCH3 gene locus with hypertension and intracerebral hemorrhage.Methods The case data,pedigree,and pathogenic genes of a patient with autosomal dominant cerebral arteriopathy accompanied by subcortical infarction and leukoencephalopathy with hypertension and cerebral hemorrhage admitted to the Department of Neurology of Qilu Hospital of Shandong University in August 2021 were retrospectively analyzed,and relevant literature at home and abroad were searched for discussion.Results The main clinical manifestations of the proband were recurrent cerebral hemorrhage,progressive decline in memory and computation,and cognitive impairment.A family survey found that 4 out of 10 people in 4 generations of the family had CADASIL symptoms of varying severity.The proband’s head MRI+MRA+SWI suggested subacute hematoma in the right occipital lobe and adjacent corpus callosum,multiple bleeding foci in the brain,high signal in white matter,and enlargement of the left ventricle.Gene test suggested that the NOTCH3 gene was a pure heterozygous mutation in one place(c.517dupAchr19:15302932p.T173Nfs∗23).Conclusions CADASIL can present not only with ischemic stroke but also with hypertension and cerebral hemorrhage.According to the clinical manifestations,imaging examination and genetic test results,the proband is consistent with the diagnosis of CADASIL,the family carries the NOTCH3 gene mutations of c.517dupAchr19:15302932p.T173Nfs∗23 may for its pedigree causes of the disease.