Department of Neurology, Concord Repatriation General Hospital, Concord, New South Wales 2139, Australia.
Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
Neuromuscul Disord. 2021 Nov;31(11):1101-1112. doi: 10.1016/j.nmd.2021.09.010. Epub 2021 Oct 2.
Facioscapulohumeral muscular dystrophy (FSHD) is a common genetic disease of the skeletal muscle with a characteristic pattern of weakness. Facioscapulohumeral muscular dystrophy type 2 (FSHD2) accounts for approximately 5% of all cases of FSHD and describes patients without a D4Z4 repeat contraction on chromosome 4. Phenotypically FSHD2 shows virtually no difference from FSHD1 and both forms of FSHD arise via a common downstream mechanism of epigenetic derepression of the transcription factor DUX4 in skeletal muscle cells. This results in expression of DUX4 and target genes leading to skeletal muscle toxicity. Over the past decade, major progress has been made in our understanding of the genetic and epigenetic architecture that underlies FSHD2 pathogenesis, as well as the clinical manifestations and disease progression. These include the finding that FSHD2 is a digenic disease and that mutations in the genes SMCHD1, DNMT3B, and more recently LRIF1, can cause FSHD2. FSHD2 is complex and it is important that clinicians keep abreast of recent developments; this review aims to serve as an update of the clinical, genetic, and molecular research into this condition.
面肩肱型肌营养不良症（FSHD）是一种常见的骨骼肌遗传性疾病，具有特征性的无力模式。面肩肱型肌营养不良症 2 型（FSHD2）约占所有 FSHD 病例的 5%，描述的是在染色体 4 上没有 D4Z4 重复收缩的患者。表型上，FSHD2 与 FSHD1 几乎没有区别，两种形式的 FSHD 都是通过骨骼肌细胞中转录因子 DUX4 的表观遗传去抑制的共同下游机制产生的。这导致 DUX4 和靶基因的表达，从而导致骨骼肌毒性。在过去的十年中，我们在理解 FSHD2 发病机制的遗传和表观遗传结构方面取得了重大进展，以及临床表现和疾病进展。这些发现包括 FSHD2 是一种双基因疾病，SMCHD1、DNMT3B 基因的突变，以及最近的 LRIF1 基因突变都可导致 FSHD2。FSHD2 很复杂，临床医生了解最新进展很重要；这篇综述旨在更新对这种疾病的临床、遗传和分子研究。
