Focke Jan K, Kraemer Markus
Department of Neurology, Alfried Krupp Hospital, Essen, Germany.
Department of Neurology, Heinrich-Heine-University Hospital, Düsseldorf, Germany.
Neurol Res Pract. 2023 Aug 17;5(1):38. doi: 10.1186/s42466-023-00268-2.
Cerebral vasculopathies frequently lead to severe medical conditions such as stroke or intracranial hemorrhage and have a broad range of possible etiologies that require different therapeutic regimens. However, vasculopathies sometimes present with characteristic angiographic findings, that - if recognized - can guide a more specific diagnostic work-up. Certain ACTA2 variants are associated with a distinctive cerebrovascular phenotype characterized by an anomalously straight course of intracranial arteries, dilatation of proximal ICA and stenosis of distal ICA, in the absence of a compensatory basal collateral network found in Moyamoya disease. Until recently, this ACTA2 cerebral arteriopathy has been reported only in ACTA2 variants impairing Arg179.
We report a familial case of a missense ACTA2 variant p.Arg198Cys with angiographic features of an ACTA2 cerebral arteriopathy. We analyzed the neuroimaging features of all four variant carrying family members and discussed the cerebrovascular abnormalities we found on the background of the current literature on ACTA2 arteriopathies.
Neuroimaging of the variant carriers revealed angiographic abnormalities characteristic for ACTA2 cerebral arteriopathy such as stenoses of the terminal internal carotid artery, occlusion of the proximal middle cerebral artery and an anomalously straight course of the intracranial arteries. In our index patient catheter angiography showed a Moyamoya-like basal collateral network alongside with the above-mentioned features of an ACTA2 cerebral arteriopathy. The detected missense ACTA2 variant p.Arg198Cys was not known to be associated a cerebral arteriopathy, so far. One of the patients later died from aortic dissection - a common vascular complication of ACTA2 variants.
The familial case expands the phenotype of the detected ACTA2 variant p.Arg198Cys and hereby broadens the range of ACTA2 variants associated with a cerebral arteriopathy. Further, it emphasizes the importance of an interdisciplinary approach of vasculopathies.
脑血管病变常导致严重的疾病，如中风或颅内出血，其病因广泛，需要不同的治疗方案。然而，血管病变有时会呈现出特征性的血管造影表现，如果能够识别这些表现，就可以指导更具针对性的诊断检查。某些ACTA2基因变异与一种独特的脑血管表型相关，其特征是颅内动脉走行异常笔直、颈内动脉近端扩张和远端狭窄，且不存在烟雾病中发现的代偿性基底侧支循环网络。直到最近，这种ACTA2脑血管病仅在损害精氨酸179的ACTA2基因变异中被报道。
我们报告了一例家族性错义ACTA2基因变异p.Arg198Cys病例，其具有ACTA2脑血管病的血管造影特征。我们分析了所有四名携带变异基因家庭成员的神经影像学特征，并结合当前关于ACTA2动脉病的文献，讨论了我们发现的脑血管异常情况。
变异基因携带者的神经影像学检查显示出ACTA2脑血管病的特征性血管造影异常，如颈内动脉末端狭窄、大脑中动脉近端闭塞以及颅内动脉走行异常笔直。在我们的索引患者中，导管血管造影显示出类似烟雾病的基底侧支循环网络，同时伴有上述ACTA2脑血管病的特征。到目前为止，检测到的错义ACTA2基因变异p.Arg198Cys尚未被认为与脑血管病相关。其中一名患者后来死于主动脉夹层——ACTA2基因变异常见的血管并发症。
该家族病例扩展了检测到的ACTA2基因变异p.Arg198Cys的表型，从而拓宽了与脑血管病相关的ACTA2基因变异范围。此外，它强调了血管病变跨学科方法的重要性。
