Torri Francesca, Ciurli Beatrice, Rende Mariaconcetta, Votta Arianna, Mocciaro Emanuele, Karakashi Frida, Lencioni Matteo, Ferraro Elisabetta, Filosto Massimiliano, Gabellini Davide, Siciliano Gabriele, Ricci Giulia
Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa, Italy.
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Acta Myol. 2025 Mar;44(1):2-10. doi: 10.36185/2532-1900-1047.
Facioscapulohumeral muscular dystrophy (FSHD) is a common genetic disorder characterized by progressive muscle weakness, especially in the face, shoulders, and upper limbs. Despite extensive research, the underlying pathogenesis and clinical variability remain incompletely understood. This review aims to summarize recent advances in FSHD research, focusing on genetic and epigenetic factors and the potential for precision medicine.
A comprehensive review of recent literature was conducted, examining molecular mechanisms such as mutations in the D4Z4 region, DUX4 expression, RNA interference (RNAi) and antisense oligonucleotides (AOs). Clinical variability was analyzed to assess different disease phenotypes. Clinical trials investigating potential treatments, especially those targeting DUX4, were also reviewed.
FSHD shows significant clinical variability, with different progression rates across phenotypes. The 4qA allele is linked to more typical forms of the disease, but epigenetic factors, including DNA methylation and miRNA expression, also influence disease severity. Despite progress, the exact molecular mechanisms driving disease expression remain unclear. Clinical trials, such as Losmapimod, show promise in slowing muscle degeneration, though results remain inconsistent.
FSHD presents significant challenges for therapy development due to its genetic complexity and clinical variability. Ongoing research is needed to clarify pathogenesis and identify reliable biomarkers. Future therapeutic strategies should focus on precision medicine, integrating genetic, clinical, and imaging data to optimize patient stratification and treatment efficacy.
面肩肱型肌营养不良症（FSHD）是一种常见的遗传性疾病，其特征为进行性肌肉无力，尤其是面部、肩部和上肢的肌肉。尽管进行了广泛研究，但潜在的发病机制和临床变异性仍未完全明确。本综述旨在总结FSHD研究的最新进展，重点关注遗传和表观遗传因素以及精准医学的潜力。
对近期文献进行全面综述，研究D4Z4区域突变、DUX4表达、RNA干扰（RNAi）和反义寡核苷酸（AO）等分子机制。分析临床变异性以评估不同的疾病表型。还综述了研究潜在治疗方法的临床试验，尤其是针对DUX4的试验。
FSHD表现出显著的临床变异性，不同表型的进展速度不同。4qA等位基因与该疾病更典型的形式相关，但包括DNA甲基化和miRNA表达在内的表观遗传因素也会影响疾病严重程度。尽管取得了进展，但驱动疾病表达的确切分子机制仍不清楚。诸如洛索洛芬等临床试验在减缓肌肉退化方面显示出前景，不过结果仍不一致。
由于其遗传复杂性和临床变异性，FSHD在治疗开发方面面临重大挑战。需要持续研究以阐明发病机制并确定可靠的生物标志物。未来的治疗策略应侧重于精准医学，整合遗传、临床和影像数据以优化患者分层和治疗效果。
