Background Becker muscular dystrophy (BMD) is an X-linked neuromuscular disease due to mutations in the DMD gene, leading to a deficient and less functional dystrophin mainly in skeletal and cardiac muscle. Understanding the natural history of BMD is crucial for optimizing patient care and developing targeted treatments. Materials and methods Retrospective data were collected from 943 patients diagnosed with BMD based on a combination of clinical, biochemical and genetic criteria followed by 17 Italian neuromuscular centers. Patients’ demographics, main signs and symptoms at BMD onset, neuropsychiatric comorbidities, age at loss of ambulation (LoA), cardiac left ventricular ejection fraction (LVEF), pulmonary forced vital capacity (FVC), and DMD mutations were collected. Disease milestones were analysed in specific DMD mutational groups. Results the median age at the last assessment was 26.0 (16.6-41.9) years, with a median age at diagnosis of 7.5 (4.0-14.0) years. In 55% of patients, the diagnosis was prompted by the incidental finding of hyperCKemia. At the last assessment, 13.5% of patients had lost the ability to walk at a median age estimated by Kaplan-Meier analysis of 69 years. Thirty percent of patients exhibited left ventricular impairment and 2.7% respiratory involvement. Ten percent of patients carried out-of-frame mutations, 4% nonsense mutations, and 86% in-frame deletions/duplications. The subset of in-frame deletions was further classified based on the specific mutations. Patients carrying del45-49 compared to del45-47 were associated with an earlier LoA (P=1×10−4), where patients with del45-55 (P=.005), del48 (P=.02), and del48-49 (P=.02) correlated with a later LoA compared to del45-47. del45-55 (P=.002) and del48 (P=.003) were significantly associated with decreased odds of developing a pathological LVEF% compared to del45-47. Conclusion Our results contribute to the better understanding of the natural history of BMD and capture precious data in the era of the emerging therapies. The knowledge of the specific DMD mutation may help to define a prognosis in a subset of BMD patients and will serve as a model for the design of future therapies.

中文翻译：

---

Becker 肌营养不良症的自然病程：DMD 基因突变可预测临床严重程度


背景 贝克尔肌营养不良症 （BMD） 是一种由 DMD 基因突变引起的 X 连锁神经肌肉疾病，主要导致骨骼肌和心肌中的肌萎缩蛋白缺乏且功能较差。了解 BMD 的自然病程对于优化患者护理和开发靶向治疗至关重要。材料和方法 根据临床、生化和遗传标准的组合，从 943 例诊断为 BMD 的患者收集回顾性资料，然后是 17 个意大利神经肌肉中枢。收集患者的人口统计学、 BMD 发病时的主要体征和症状、神经精神合并症、行走丧失年龄 （LoA） 、心脏左心室射血分数 （LVEF） 、肺用力肺活量 （FVC） 和 DMD 突变。分析特定 DMD 突变组的疾病里程碑。结果 最后一次评估的中位年龄为 26.0 （16.6-41.9） 岁，诊断时的中位年龄为 7.5 （4.0-14.0） 岁。在 55% 的患者中，诊断是由高 CK血症的偶然发现引起的。在最后一次评估中，13.5% 的患者在 Kaplan-Meier 分析估计的中位年龄为 69 岁时失去了行走能力。30% 的患者表现出左心室损害和 2.7% 的呼吸受累。10% 的患者进行了框外突变、4% 的无义突变和 86% 的框内缺失/重复。框内缺失的子集根据特定突变进一步分类。与 del45-47 相比，携带 del45-49 的患者与较早的 LoA 相关 （P=1×10−4），其中 del45-55 （P=.005）、del48 （P=.02） 和 del48-49 （P=.02） 的患者与 del45-47 相比，与较晚的 LoA 相关。del45-55 （P=.002） 和 del48 （P=.003） 与 del45-47 相比，发生病理性 LVEF% 的几率显著降低。结论我们的结果有助于更好地了解 BMD 的自然史，并在新兴疗法时代捕获宝贵的数据。对特定 DMD 突变的了解可能有助于确定 BMD 患者亚群的预后，并将作为未来疗法设计的模型。