METHODS: Based on the multicenter collaborating effort of the Pan-Yangtze River Delta Alliance for Neuromuscular Disorders, patients with suspected clinical diagnoses of DM1 were genetically confirmed from January 2020 to April 2023. Peak CTG repeats in the DMPK gene were analyzed using triplet repeat-primed PCR (TP-PCR) and flanking PCR. Time-to-event analysis of onset age in females and males was performed. Additionally, detailed clinical features and longitudinal changes from the disease onset in 64 DM1 patients were retrospectively collected and analyzed. The Epworth Sleepiness Scale and Fatigue Severity Scale were used to quantify the severity of daytime sleepiness and fatigue.
RESULTS: Among the 211 genetically confirmed DM1 patients, the mean age at diagnosis was 40.9 ± 12.2 (range: 12-74) with a male-to-female ratio of 124:87. The average size of CTG repeats was 511.3 (range: 92-1945). Among the DM1 patients with comprehensive clinical data (n = 64, mean age 41.0 ± 12.0), the age at onset was significantly earlier in males than in females (4.8 years earlier, p = 0.026). Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features. The predominant involved muscles at onset are hands (weakness or myotonia) (52.6%) and legs (walking disability) (42.1%). Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes. Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment. Chinese patients exhibited smaller size of CTG repeats (468 ± 139) than those reported in Italy (613 ± 623), the US (629 ± 386), and Japan (625 [302, 1047]), and milder phenotypes with less multisystem involvement.
CONCLUSIONS: The Chinese Han DM1 patients presented milder phenotypes compared to their Caucasian and Japanese counterparts. A male predominance and an early age of onset were identified in male Chinese Han DM1 patients.
方法:基于泛长三角神经肌肉疾病联盟的多中心合作,从2020年1月至2023年4月,疑似DM1临床诊断的患者获得了基因确诊.使用三联体重复引发的PCR(TP-PCR)和侧翼PCR分析DMPK基因中的峰CTG重复。对女性和男性的发病年龄进行了事件发生时间分析。此外,回顾性收集并分析了64例DM1患者的详细临床特征和发病后的纵向变化.采用Epworth嗜睡量表和疲劳严重程度量表量化日间嗜睡和疲劳的严重程度。
结果:在211名基因证实的DM1患者中,诊断时的平均年龄为40.9±12.2(范围:12-74),男女比例为124:87.CTG重复的平均大小为511.3(范围:92-1945)。在临床资料全面的DM1患者中(n=64,平均年龄41.0±12.0),男性的发病年龄明显早于女性(早4.8岁,p=0.026)。肌肉无力(92.2%),肌强直(85.9%),疲劳(73.4%)是最常见的临床特征。发病时主要涉及的肌肉是手(无力或肌强直)(52.6%)和腿(行走障碍)(42.1%)。其中,70.3%的患者有日间嗜睡,14.1%的人接受了白内障手术,7.8%使用轮椅,4.7%需要通气支持,1.6%需要胃管。关于合并症,4.7%的患者有肿瘤,17.2%有糖尿病,23.4%有呼吸困难,28.1%有间歇性失眠,43.8%有吞咽困难,25%表现为认知障碍。中国患者的CTG重复序列(468±139)比意大利(613±623)小,美国(629±386),和日本(625[302,1047]),和较温和的表型,多系统参与较少。
结论:与白种人和日本人相比,中国汉族DM1患者表现出更温和的表型。在男性中国汉族DM1患者中发现男性占优势,发病年龄较早。