BACKGROUND Congenital mydriasis and retinal arteriolar tortuosity are associated with the life-threatening multisystemic smooth muscle dysfunction syndrome (MSMDS) due to mutations in the gene, ACTA2, which encodes alpha-smooth muscle actin (α-SMA). Previous reports attributed MSMDS-related congenital mydriasis to the absence of iris sphincter muscle. Similarly, it has been hypothesized that abnormal proliferation of the vascular smooth muscle cells causes the marked tortuosity of retinal arterioles in MSMDS. In this report, high-resolution ocular imaging reveals unexpected findings that reject previous hypotheses. CASE PRESENTATION The proband is a 37-year-old female with a history of neonatal patent ductus arteriosus (PDA) ligation, left-sided choreiform movements at the age of 11 and a transient aphasia with right-sided weakness at the age of 30. Her older sister also had PDA ligation and congenital mydriasis but no neurological deficit up to age 41. Magnetic resonance angiogram demonstrated cerebrovascular lesions resembling but distinct from Moyamoya disease, characterised by internal carotid artery dilatation, terminal segment stenosis and absent basal collaterals. Their mother had poorly reactive pupils with asymptomatic cerebral arteriopathy resembling her daughters. All three had prominent retinal arteriolar tortuosity. The daughters were heterozygous and the mother was a somatic mosaic for a novel c.351C > G (p.Asn117Lys) transversion in ACTA2. Iris optical coherence tomography (OCT) showed a hyporeflective band anterior to the pigment epithelium indicating the presence of dysfunctional sphincter muscle. Adaptive optics retinal imaging showed no thickening of the arteriolar vessel wall whilst OCT angiography showed extreme corkscrew course of arterioles suggesting vessel elongation. CONCLUSIONS In addition to the known association between Met46, Arg179 and Arg258 substitutions and ACTA2-related arteriopathy, this case illustrates the possibility that Asn117 also plays an important role in α-SMA function within the cerebrovascular smooth muscle cell. MSMDS-related congenital mydriasis is due to reduced iris sphincter contractility rather than its absence. Retinal arteriolar tortuosity might be due to longitudinal proliferation of arteriolar smooth muscle cells. The described cerebrovascular and ocular signs are consistent with predicted effects of the novel Asn117Lys substitution in ACTA2.

中文翻译：

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多系统平滑肌功能障碍综合征的高分辨率虹膜和视网膜成像归因于ACTA2中的新型Asn117Lys替代：一例病例报告。

背景技术由于编码α-平滑肌肌动蛋白（α-SMA）的ACTA2基因突变，使先天性散瞳和视网膜小动脉曲折与威胁生命的多系统平滑肌功能障碍综合征（MSMDS）相关。先前的报道将与MSMDS相关的先天性瞳孔散大归因于虹膜括约肌的缺失。类似地，已经假设在MSMDS中，血管平滑肌细胞的异常增殖会引起视网膜小动脉的曲折。在本报告中，高分辨率眼科成像揭示了意料之外的发现，这些发现拒绝了先前的假设。病例表述先证者是一名37岁的女性，有新生儿动脉导管未闭（PDA）结扎的历史，11岁时出现左侧脉络膜样运动，30岁时出现暂时性失语，右侧无力。她的姐姐也有PDA结扎和先天性瞳孔散大，但直到41岁时都没有神经功能障碍。磁共振血管造影显示脑血管病变与Moyamoya病相似但与Moyamoya病不同，其特征是颈内动脉扩张，末段狭窄和基底侧支缺失。他们的母亲的瞳孔反应很差，患有无症状的脑动脉病，类似于她的女儿。这三者均具有突出的视网膜小动脉曲折。女儿是杂合子，母亲是体细胞嵌合体，在ACTA2中发生了新的c.351C> G（p.Asn117Lys）转化。虹膜光学相干断层扫描（OCT）显示色素上皮细胞前面有一条低反射带，表明存在括约肌功能障碍。自适应光学视网膜成像显示小动脉血管壁没有增厚，而OCT血管造影显示小动脉的开瓶过程极端，提示血管延长。结论除了已知的Met46，Arg179和Arg258替代与ACTA2相关的动脉病变之间的关联外，这种情况还说明了Asn117在脑血管平滑肌细胞内的α-SMA功能中也起重要作用的可能性。MSMDS相关的先天性瞳孔散大是由于虹膜括约肌收缩力降低，而不是其不存在。视网膜小动脉曲折可能是由于小动脉平滑肌细胞的纵向增殖所致。