Background

Dominant gamma-smooth muscle actin gene (ACTG2) variants cause clinically diverse forms of visceral myopathy. Many patients undergo intestinal resection or biopsy before identification of their genetic defect. The pathology of ACTG2-variant visceral myopathy has not been evaluated systematically.

Methods

Glass slides, ultrastructural images, molecular genetic reports, and clinical records from 16 patients with pathogenic (15) or likely pathogenic (1) ACTG2 variants were reviewed and compared with surgical specimens from controls (no evidence of a primary myopathy or pseudo-obstruction due to Hirschsprung disease) and published descriptions.

Results

The variable clinical manifestations in our cohort matched those in the literature. Only non-specific light and electron microscopic findings observed in non-myopathic controls were encountered in 13 of 16 patients. The remaining 3 patients harbored hyalinized cytoplasmic inclusions in smooth muscle cells and 1 of them had polyglucosan bodies in the muscularis propria.

Conclusions

Apart from hyalinized inclusions, which were only observed in 3/16 patients, intestinal pathology in the majority of patients with ACTG2 variants is not indicative of an underlying visceral myopathy. Molecular testing should be considered even when no diagnostic intestinal pathology is identified.

中文翻译：

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致病性 ACTG2 变异内脏肌病患者的肠道病理学：来自 12 个家庭的 16 名患者和文献回顾

背景

显性 γ-平滑肌肌动蛋白基因 ( ACTG2 ) 变异导致临床上多种形式的内脏肌病。许多患者在确定其遗传缺陷之前接受了肠道切除术或活检。ACTG2 变异内脏肌病的病理学尚未得到系统评价。

方法

审查了 16 名具有致病性 (15) 或可能致病性 (1) ACTG2变异的患者的载玻片、超微结构图像、分子遗传学报告和临床记录，并与来自对照组的手术标本进行了比较（没有证据表明原发性肌病或假性梗阻由于Hirschsprung 病）和发表的描述。

结果

我们队列中的可变临床表现与文献中的相匹配。在 16 名患者中的 13 名中仅遇到在非肌病对照中观察到的非特异性光和电子显微镜检查结果。其余 3 例患者在平滑肌细胞中有玻璃样胞质包涵体，其中 1 例在固有肌层有聚葡聚糖小体。

结论

除了仅在 3/16 患者中观察到的透明包涵体外，大多数ACTG2变异患者的肠道病理学并不表明存在潜在的内脏肌病。即使没有发现诊断性肠道病理学，也应考虑进行分子检测。