Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1

**Background:** Myotonic dystrophy type 1 (DM1) is the most common adult muscular dystrophy worldwide, caused by CTG repeat expansion in the DMPK gene. While well-characterized in Caucasian populations, large cohort data from China are lacking. This study aimed to analyze the genetic and clinical features of Chinese Han DM1 patients through a multicenter collaboration.

**Methods:** From January 2020 to April 2023, patients with suspected DM1 were enrolled via the Pan-Yangtze River Delta Alliance for Neuromuscular Disorders (PYDAN) network. Genetic confirmation was performed using triplet repeat-primed PCR (TP-PCR) and flanking PCR to measure peak CTG repeats in DMPK. Among 230 clinically suspected individuals, 211 were genetically confirmed (91.7%). Detailed clinical data were retrospectively collected for 64 patients, including demographics, first symptoms, comorbidities, and scales (Epworth Sleepiness Scale [ESS] and Fatigue Severity Scale [FSS]). Daytime sleepiness was defined as ESS ≥36, fatigue as FSS ≥10. Time-to-event analysis of onset age by sex was performed using the Log-rank test.

**Key Results:** The 211 genetically confirmed patients had a mean age of 40.9±12.2 years (range 12–74) and a male-to-female ratio of 124:87. Mean peak CTG repeats were 511.3 (range 92–1945). Among the 64 patients with detailed data (mean age 41.0±12.0, 56.2% male, mean CTG repeats 468±139), the most common clinical features were muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%). First symptoms most often involved hand muscles (weakness or myotonia, 52.6%) and legs (walking disability, 42.1%). Additional findings included daytime sleepiness (70.3%), cataract surgery (14.1%), wheelchair use (7.8%), ventilatory support (4.7%), gastric tube use (1.6%), diabetes (17.2%), dyspnea (23.4%), intermittent insomnia (28.1%), dysphagia (43.8%), cognitive impairment (25%), and tumors (4.7%, all thyroid cancer). Time-to-event analysis showed significantly earlier onset in males by 4.8 years (p=0.026). Compared to published data from Italy (613±623), the US (629±386), and Japan (625 [302, 1047]), Chinese patients had smaller CTG repeats and lower rates of cataracts (14% vs. 26–78%) and cardiac defects (not reported in this study vs. 19–79% in others).

**Clinical Implications:** This study demonstrates that Chinese Han DM1 patients have a milder phenotype with smaller CTG expansions and less multisystem involvement compared to Caucasian and Japanese populations. The male predominance and earlier onset in males suggest sex-specific factors may influence disease severity. These findings highlight the importance of ethnic-specific data for diagnosis, prognosis, and management of DM1. The lower prevalence of cataracts and cardiac issues may reduce the need for routine screening in Chinese patients, but the high rates of daytime sleepiness (70.3%) and fatigue (73.4%) warrant clinical attention. Limitations include the retrospective design, potential selection bias, and inability to assess somatic mosaicism.