Department of Neurology, Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK.
Brain. 2012 Aug;135(Pt 8):2506-14. doi: 10.1093/brain/aws172. Epub 2012 Jul 24.
Mutations in the ACTA2 gene lead to diffuse and diverse vascular diseases; the Arg179His mutation is associated with an early onset severe phenotype due to global smooth muscle dysfunction. Cerebrovascular disease associated with ACTA2 mutations has been likened to moyamoya disease, but appears to have distinctive features. This study involved the analysis of neuroimaging of 13 patients with heterozygous missense mutations in ACTA2 disrupting Arg179. All patients had persistent ductus arteriosus and congenital mydriasis, and variable presentation of pulmonary hypertension, bladder and gastrointestinal problems associated with this mutation. Distinctive cerebrovascular features were dilatation of proximal internal carotid artery, occlusive disease of terminal internal carotid artery, an abnormally straight course of intracranial arteries, and absent basal 'moyamoya' collaterals. Patterns of brain injury supported both large and small vessel disease. Key differences from moyamoya disease were more widespread arteriopathy, the combination of arterial ectasia and stenosis and, importantly, absence of the typical basal 'moyamoya' collaterals. Evaluation of previously published cases suggests some of these features are also seen in the ACTA2 mutations disrupting Arg258. The observation that transition from dilated to normal/stenotic arterial calibre coincides with where the internal carotid artery changes from an elastic to muscular artery supports the hypothesis that abnormal smooth muscle cell proliferation caused by ACTA2 mutations is modulated by arterial wall components. Patients with persistent ductus arteriosus or congenital mydriasis with a label of 'moyamoya' should be re-evaluated to ensure the distinctive neuroimaging features of an ACTA2 mutation have not been overlooked. This diagnosis has prognostic and genetic implications, and mandates surveillance of other organ systems, in particular the aorta, to prevent life-threatening aortic dissection.
ACTA2 基因突变可导致弥漫性和多样性的血管疾病；Arg179His 突变与由于平滑肌功能障碍导致的早发性严重表型相关。与 ACTA2 突变相关的脑血管疾病类似于 moyamoya 病，但似乎具有独特的特征。本研究分析了 13 名杂合错义突变的神经影像学，这些突变破坏了 ACTA2 的 Arg179。所有患者均存在持续性动脉导管未闭和先天性瞳孔散大，以及可变的肺动脉高压、膀胱和胃肠道问题与该突变相关。独特的脑血管特征是颈内动脉近端扩张、颈内动脉终末闭塞、颅内动脉异常笔直的走行和基底“moyamoya”侧支血管缺失。脑损伤模式支持大血管和小血管疾病。与 moyamoya 病的关键区别在于更广泛的血管病变、动脉扩张和狭窄的组合，以及重要的是，基底“moyamoya”侧支血管的缺失。对先前发表的病例的评估表明，Arg258 破坏的 ACTA2 突变也存在这些特征。从扩张到正常/狭窄动脉口径的转变与颈内动脉从弹性动脉转变为肌性动脉的位置相吻合，这支持了 ACTA2 突变导致的平滑肌细胞异常增殖受动脉壁成分调节的假说。存在持续性动脉导管未闭或先天性瞳孔散大的“moyamoya”标签的患者应重新评估，以确保没有忽略 ACTA2 突变的独特神经影像学特征。该诊断具有预后和遗传意义，需要监测其他器官系统，特别是主动脉，以防止危及生命的主动脉夹层。
