Comprehensive analysis of 2097 Patients with Dystrophinopathy Based on a Database From 2011 to 2021

Abstract

Abstract Background A growing number of clinical trials for new therapeutic strategies are being conducted or considered for dystrophinopathy. Detailed data on natural history will facilitate the evaluation of the effectiveness of new drugs for this rare disease. Nevertheless, there is a paucity of data regarding the long-term natural history and associated management in China. Here, we provide a comprehensive description of associated clinical and molecular findings and treatment outcomes in the Chinese population. Methods Institutional data on all patients with dystrophinopathy from August 2011 to August 2021 were reviewed retrospectively. The data included geographic distribution, age at diagnosis, genetic analysis, and treatment such as corticosteroids, cardiac interventions, and clinical outcomes. Results In total, 2097 patients with dystrophinopathy, including 1703 Duchenne muscular dystrophy (DMD), 311 Becker muscular dystrophy (BMD), 46 intermediate muscular dystrophy (IMD), and 37 “pending” (individuals with an undetermined phenotype) were registered in the Children’s Hospital of Fudan University database for dystrophinopathy from August 2011 to August 2021. The spectrum of identified mutations included exon deletions (66.7%), exon duplications (10.7%), nonsense mutations (10.3%), splice-site mutations (4.5%), small deletions (3.5%), small insertions (1.8%), and missense mutations (0.9%). Two deep intronic mutations were identified. Regarding treatment, 54.4% of DMD patients and 39.1% of IMD patients were treated with glucocorticoids. The median age at loss of ambulation was 2.5 years later in DMD patients with glucocorticoid treatment. Overall, 7.4% of DMD, 8.3% of IMD, and 2.6% of BMD patients were prescribed one cardiac medicine at least, and four DMD patients were under ventilator support. Those eligible for exon skipping therapy included 55.3% of DMD patients; among them, 12.9%, 10%, and 9.6% of these patients were eligible for skipping exons 51, 53, and 45. Conclusions This is one of the largest studies to have evaluated the natural history of dystrophinopathy in China, which is particularly conducive to recruiting eligible patients for clinical trials and providing real-world data to support drug development.