强直性肌营养不良1型和2型的性别相关表型差异：一项来自塞尔维亚的全国性注册研究

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中文摘要

背景： 强直性肌营养不良（DM）是常染色体显性的多系统疾病，临床表现多样。DM1和DM2具有重叠特征，如肌强直和肌无力，但在发病年龄、严重程度、进展和多系统表现方面存在差异。新出现的证据提示生物学性别影响疾病表现、进展和结局。
目的： 评估经基因确诊的DM1和DM2患者中性别特异性差异。
患者和方法： 这项横断面研究纳入来自塞尔维亚强直性肌营养不良注册处的587例成年患者（391例DM1，196例DM2）。综合评估包括神经肌肉检查、电生理检测、系统性评估（心脏、呼吸、内分泌、骨骼和眼科）、实验室分析以及功能状态。肌力采用改良医学研究委员会评分进行测量。统计分析比较每种DM类型内的男性和女性患者。鉴于本研究的探索性性质，未进行多重比较校正。
结果： 在DM1中，男女比例为1.1:1。男性表现出更严重的神经肌肉受累，包括远端上肢和近端下肢肌力较低、肌强直持续时间更长、构音障碍、吞咽困难、多发性神经病、骨骼畸形、秃发和不育的患病率更高，以及心电图异常更常见。在DM2中，女性占多数（比例1.5:1），并表现出更明显的近端下肢无力、呼吸能力下降以及白内障更常见。DM2男性肌强直持续时间更长，多发性神经病、秃发、不育、高血糖的患病率更高，并且更常植入起搏器。
结论： 性别与DM1和DM2中不同的表型特征相关。DM1男性和DM2女性可见更大的神经肌肉负担。另一方面，在DM1和DM2中，男性患者总体上表现出更多的心脏和内分泌/代谢负担。将性别作为变量纳入临床评估、风险分层和治疗规划，对于未来DM患者的个体化管理可能至关重要。

英文摘要

BACKGROUND: Myotonic dystrophies (DM) are autosomal dominant, multisystem disorders with variable clinical expressions. DM1 and DM2 share overlapping features, such as myotonia and muscle weakness, but differ in age at onset, severity, progression and multisystem features. Emerging evidence suggests that biological sex influences disease manifestations, progression, and outcomes.
OBJECTIVE: To assess sex-specific differences among patients with genetically confirmed DM1 and DM2.
PATIENTS AND METHODS: This cross-sectional study included 587 adult patients (391 DM1, 196 DM2) from the Serbian Registry for Myotonic Dystrophies. Comprehensive assessments included neuromuscular examination, electrophysiological testing, systemic evaluation (cardiac, respiratory, endocrine, skeletal, and ophthalmologic), laboratory analysis, and functional status. Muscle strength was measured using a modified Medical Research Council score. Statistical analyses compared male and female patients within each DM type. Given the exploratory nature of the study, no adjustment for multiple comparisons was applied.
RESULTS: In DM1, the male-to-female ratio was 1.1:1. Males exhibited more severe neuromuscular involvement, including less strength in distal upper limb and proximal lower limb, longer myotonia duration, higher prevalence of dysarthria, dysphagia, polyneuropathy, skeletal deformities, baldness, and infertility, as well as more common impairment on ECG. In DM2, females predominated (ratio 1.5:1) and showed more pronounced weakness in proximal lower limb, reduced respiratory capacity, and more common cataracts. DM2 males had longer myotonia, higher prevalence of polyneuropathy, baldness, infertility, hyperglycemia, and more frequent pacemaker implantation.
CONCLUSIONS: Sex is associated with distinct phenotypic profiles in DM1 and DM2. Greater neuromuscular burden was seen in DM1 males and DM2 females. On the other hand, male patients generally exhibit more cardiologic and endocrinological/metabolic burden in both DM1 and DM2. Incorporating sex as a variable in clinical evaluation, risk stratification, and therapeutic planning may be essential for personalized management of DM patients in future.