Abstract：
Pathogenic variants in the skeletal muscle α-actin 1 gene (ACTA1) cause a spectrum of myopathies with clinical and myopathological diversity. Clinical presentations occur from the prenatal period to adulthood, commonly with proximal-predominant weakness and rarely preferential distal weakness. Myopathological findings are wide-ranging, with nemaline rods being most frequent. Associated cardiomyopathy is rare and conduction defects are not reported. We describe a family with congenital myopathy with prominent finger flexor weakness and cardiomyopathy with cardiac conduction defects. The proband, a 48-year-old Caucasian male, his 73-year-old mother, 41-year-old sister, and 19-year-old nephew presented with prominent finger flexor weakness on a background of neonatal hypotonia and delayed motor milestones. All had progressive cardiomyopathy with systolic dysfunction and/or left ventricular dilation. The proband and sister had intraventricular conduction delay and left anterior fascicular block, respectively. The mother had atrial fibrillation. Muscle biopsy in the proband and sister demonstrated congenital fiber-type disproportion and rare nemaline rods in the proband. A novel dominant variant in ACTA1 (c.81C>A, p.Asp27Glu) segregated within the family. This family expands the genotypic and phenotypic spectrum of ACTA1-related myopathy, highlighting preferential finger flexor involvement with cardiomyopathy and conduction disease. We emphasize early and ongoing cardiac surveillance in ACTA1-related myopathy.
摘要：
骨骼肌α-肌动蛋白1基因（ACTA1）的致病变异导致一系列具有临床和肌肉病理学多样性的肌病。临床表现从产前到成年，通常有近端占优势的弱点和很少优先远端弱点。肌病的发现范围很广,最常见的是线虫棒。相关的心肌病很少见，没有报道传导缺陷。我们描述了一个患有先天性肌病的家庭，伴有明显的手指屈肌无力和伴有心脏传导缺陷的心肌病。先证者，一个48岁的白人男性,他73岁的母亲,41岁的姐姐,19岁的侄子在新生儿张力减退和运动里程碑延迟的背景下表现出明显的手指屈肌无力。所有患者均患有进行性心肌病，伴有收缩功能障碍和/或左心室扩张。先证者和姐妹有脑室内传导延迟和左前分支传导阻滞，分别。母亲有心房颤动。先证者和姐妹的肌肉活检显示先证者中先天性纤维型不相称和罕见的线虫棒。ACTA1中的一种新的显性变体（c.81C>A，p.Asp27Glu）在家庭中隔离。该家族扩展了ACTA1相关肌病的基因型和表型谱，突出手指屈肌优先受累心肌病和传导疾病。我们强调ACTA1相关肌病的早期和持续心脏监测。
