Folkhälsan Research Center.
Department of Medical Genetics, Medicum, University of Helsinki, Helsinki, Finland.
Curr Opin Neurol. 2024 Oct 1;37(5):515-522. doi: 10.1097/WCO.0000000000001299. Epub 2024 Jul 16.
Distal myopathies are a clinically heterogenous group of rare, genetic muscle diseases, that present with weakness in hands and/or feet at onset. Some of these diseases remain accentuated in the distal muscles whereas others may later progress to the proximal muscles. In this review, the latest findings related to genetic and clinical features of distal myopathies are summarized.
Variants in SMPX , DNAJB2, and HSPB6 have been identified as a novel cause of late-onset distal myopathy and neuromyopathy. In oculopharyngodistal myopathies, repeat expansions were identified in two novel disease-causing genes, RILPL1 and ABCD3. In multisystem proteinopathies, variants in HNRNPA1 and TARDBP , genes previously associated with amyotrophic lateral sclerosis, have been shown to cause late-onset distal myopathy without ALS. In ACTN2 -related distal myopathy, the first recessive forms of the disease have been described, adding it to the growing list of genes were both dominant and recessive forms of myopathy are present.
The identification of novel distal myopathy genes and pathogenic variants contribute to our ability to provide a final molecular diagnosis to a larger number of patients and increase our overall understanding of distal myopathy genetics and pathology.
远端肌病是一组临床异质性的罕见遗传性肌肉疾病，以手部和/或足部无力为首发症状。其中一些疾病仍以远端肌肉为主，而另一些疾病可能随后进展至近端肌肉。本文总结了远端肌病的遗传和临床特征的最新发现。
SMPX、DNAJB2 和 HSPB6 的变异被确定为导致迟发性远端肌病和神经肌病的新原因。在眼咽远端肌病中，两个新的致病基因 RILPL1 和 ABCD3 中发现了重复扩展。在多系统蛋白病中，先前与肌萎缩侧索硬化症相关的 HNRNPA1 和 TARDBP 基因的变异也被证明可导致无肌萎缩侧索硬化症的迟发性远端肌病。在 ACTN2 相关的远端肌病中，已描述了该疾病的首个隐性形式，使其成为既有显性又有隐性形式肌病的基因的不断增加的列表中的一部分。
新型远端肌病基因和致病性变异的发现有助于我们为更多患者提供最终的分子诊断，并提高我们对远端肌病遗传学和病理学的整体认识。
