Abstract：
BACKGROUND: Inherited nemaline myopathy is one of the most common congenital myopathies. This genetically heterogeneous disease is defined by the presence of nemaline bodies in muscle biopsy. The phenotypic spectrum is wide and cognitive involvement has been reported, although not extensively evaluated.
METHODS: We report two nemaline myopathy patients presenting pronounced central nervous system involvement leading to functional compromise and novel facial and skeletal dysmorphic findings, possibly expanding the disease phenotype.
RESULTS: One patient had two likely pathogenic NEB variants, c.2943G > A and c.8889 + 1G > A, and presented cognitive impairment and dysmorphic features, and the other had one pathogenic variant in ACTA1, c.169G > C (p.Gly57Arg), presenting autism spectrum disorder and corpus callosum atrophy. Both patients had severe cognitive involvement despite milder motor dysfunction.
CONCLUSIONS: We raise the need for further studies regarding the role of thin filament proteins in the central nervous system and for a systematic cognitive assessment of congenital myopathy patients.
METHODS: We report two nemaline myopathy patients presenting pronounced central nervous system involvement leading to functional compromise and novel facial and skeletal dysmorphic findings, possibly expanding the disease phenotype.
RESULTS: One patient had two likely pathogenic NEB variants, c.2943G > A and c.8889 + 1G > A, and presented cognitive impairment and dysmorphic features, and the other had one pathogenic variant in ACTA1, c.169G > C (p.Gly57Arg), presenting autism spectrum disorder and corpus callosum atrophy. Both patients had severe cognitive involvement despite milder motor dysfunction.
CONCLUSIONS: We raise the need for further studies regarding the role of thin filament proteins in the central nervous system and for a systematic cognitive assessment of congenital myopathy patients.
摘要：
背景：遗传性线虫肌病是最常见的先天性肌病之一。这种遗传异质性疾病是由肌肉活检中存在线虫体定义的。表型谱广泛，认知参与已有报道，虽然没有广泛评估。
方法：我们报告了两名表现出明显的中枢神经系统受累导致功能受损和新颖的面部和骨骼畸形的线虫性肌病患者，可能扩大疾病表型。
结果：一名患者有两种可能的致病性NEB变异，c.2943G>A和c.8889+1G>A，并呈现认知障碍和畸形特征，另一个在ACTA1中有一个致病变异，c.169G>C（p。Gly57Arg),呈现自闭症谱系障碍和call体萎缩。尽管运动功能障碍较轻，但两名患者均有严重的认知参与。
结论：我们提出需要进一步研究纤丝蛋白在中枢神经系统中的作用，并对先天性肌病患者进行系统的认知评估。
方法：我们报告了两名表现出明显的中枢神经系统受累导致功能受损和新颖的面部和骨骼畸形的线虫性肌病患者，可能扩大疾病表型。
结果：一名患者有两种可能的致病性NEB变异，c.2943G>A和c.8889+1G>A，并呈现认知障碍和畸形特征，另一个在ACTA1中有一个致病变异，c.169G>C（p。Gly57Arg),呈现自闭症谱系障碍和call体萎缩。尽管运动功能障碍较轻，但两名患者均有严重的认知参与。
结论：我们提出需要进一步研究纤丝蛋白在中枢神经系统中的作用，并对先天性肌病患者进行系统的认知评估。
