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目的观察Duchenne肌营养不良(Duchenne Muscular Dystrophy,DMD)患儿血清心肌酶谱是否随病程进展变化及其规律。方法回顾性分析1984—2011年299例来中国医科大学附属盛京医院发育儿科就诊的DMD患儿血清心肌酶谱水平,包括天冬氨酸转移酶(AST)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)和α-羟丁酸脱氢酶(α-HBDH)。依据发病特点将DMD患儿不同年龄段分为3组:<5岁组、5～<10岁组、≥10岁组。所有数据资料经方差齐性及正态分布检验,计量资料取对数后符合正态分布规律进行分析。结果 DMD患儿各年龄组心肌酶谱均显著升高,且<5岁组、5～<10岁组心肌酶谱升高最明显,≥10岁组心肌酶谱显著低于<5岁组、5～<10岁组。结论 DMD患儿血清心肌酶谱10岁升高最明显,之后随年龄增加呈下降趋势,这种变化规律可以反映肌纤维坏死速率和病程进展速度。     

Duchenne肌营养不良基因突变与智力关系的研究进展

随着分子生物学技术水平的不断提高,近年来对Duchenne肌营养不良(DMD)基因突变类型与智力发育关系的研究不断深入.DMD患儿的智力水平与基因突变类型存在一定的联系,DMD基因突变发生在45号外显子后,尤其是63号外显子后的患者发生智力低下的程度大于发生在45号之前外显子的突变,提示DMD基因突变越接近3'端越有可能导致智力低下.     

Duchenne型进行性肌营养不良40例临床分析

目的 探讨Duchenne型进行性肌营养不良(DMD)的临床特点及肌酶、肌电图、肌肉活检的诊断价值.方法 对40例经dystrophin蛋白检测确诊的DMD患儿的临床特征及实验室检查资料进行分析.结果 40例患儿平均年龄7.2岁,平均发病年龄4.5岁,15%患儿有家族史.40例患儿均有典型的临床症状和体征,肌酶升高以肌酸磷酸激酶(CPK)升高为主,≤8岁年龄组CPK值高于＞8岁组.所有患儿肌肉活检均有肌纤维变性和坏死,12.5%的患儿尚伴炎性细胞浸润.在有肌源性损害同时,15%的患儿肌电图尚有神经源性损害.结论 血清肌酶、肌电图及肌活检是DMD重要的辅助诊断指标,对于肌电图有神经源性损害和肌活检病理检查有炎性细胞浸润者,应进行基因检测和(或)dystrophin蛋白检测.     

Duchenne肌营养不良患儿的智力特点及与基因突变关系初步探讨

目的：了解国内Duchenne肌营养不良（DMD）患儿智力水平及智力低下的比例,初步探讨DMD患儿智力的结构特点及与基因突变类型的关系。方法：选择2009年1月至2011年3月的102例DMD患儿,其中84例患儿通过多重连接依赖式探针扩增（MLPA）方法进行DMD基因检测。102例DMD患儿中,选择≥6岁的50例DMD患儿作为DMD组;另选取50例年龄、性别与DMD组匹配的健康体检儿童作为对照组。采用韦氏智力量表对两组儿童进行智力及智力结构分析。结果：102例DMD患儿的平均智商为84±21,其中30例（29.4%）总智商低于70。DMD组患儿总智商、言语智商、操作智商及其11项分测验得分均显著低于对照组（P<0.01）。其中DMD基因56-79号外显子突变患儿的智商最低(59.3±11.9),另外,45-55号外显子突变患儿的智商(88.6±1.9) 明显低于1-29号(97.5±9.6)和30-44号(102.8±3.8)外显子突变的患儿（P<0.01）。结论：DMD患儿的总智商、言语智商、操作智商均显著低于正常儿童。DMD患儿智力低下与基因突变存在联系。     

Duchenne型肌营养不良患儿认知损害的研究进展北大核心CSCD

Duchenne型肌营养不良(DMD)是由于抗肌萎缩蛋白基因突变所致的X连锁隐性遗传性神经肌肉病,约1/3的患儿存在认知损害,早期发现认知损害并给予适当干预对改善患儿生存质量具有重要意义。现就近年来关于DMD患儿认知损害的临床特点、发病机制、脑结构改变和干预措施等方面的研究进展作一综述。     

Research progress on neurodevelopmental disorders in children with Duchenne muscular dystrophy北大核心CSCD

Duchenne muscular dystrophy (DMD) is a disease inherited in an X - linked recessive pattern, which is caused by the pathogenic mutation of the gene encoding Dystrophin. An increasing number of studies have confirmed the high risk of neurodevelopmental disorders in children with DMD, and that related comorbidities have distinct clinical characteristics. In this article, the research progress on neurodevelopmental disorders in children with DMD was reviewed to clarify the prevalence, clinical characteristics and high - risk factors of neurodevelopmental disorders in children with DMD. DMD therapy teams should pay attention to the evaluation, interpretation and early intervention of neurodevelopmental disorders in clinic practice, so as to improve the life quality of DMD children and help them to better integrate into the society. © 2022 ＣｈｉｎＪＡｐｐｌＣｌｉｎＰｅｄｉａｔ. All rights reserved.     

Duchenne型肌营养不良171例临床表型与基因型特征分析

目的 探讨Duchenne型肌营养不良(DMD)患儿临床表型与基因型的特点.方法 收集2014年1月至2020年6月经临床及基因检查确诊为DMD的171例患儿的临床资料,对其临床表现和基因变异结果进行分析.结果 171例患儿中男165、女6例;中位年龄4.1(1.7～7.0)岁,其中<1岁21例,～3岁41例,～7岁6...     

Duchenne肌营养不良患儿的智力及与孤独症谱系障碍的关系研究

目的 探讨Duchenne肌营养不良(DMD)患儿的智力水平和智力结构特点,以及与孤独症谱系障碍(ASD)关系及其所占比例.方法 收集2006年1月-2010年5月诊断的DMD患儿118例(其中78例已经dystrophin基因确诊),应用修订的韦氏儿童智力量表-中国版(C-WISC)和美国精神疾病诊断统计手册(DSM-Ⅳ)结合儿童孤独症评定量表(CARS)对其进行智力及智力结构分析和孤独症谱系障碍评估.结果 118例DMD患儿中有39例进行了智力测定,其中有12例总智商(FIQ)低于70,占30.8%(12/39),轻度智力低下7例(50≤IQ<70),中、重度智力低下5例(IQ<50);DMD患儿总智商、言语智商(VIQ)、操作智商(PIQ)及其11项分测验得分中,除图形拼凑与对照组差异无统计学意义(P=0.237),其余均低于对照组(P<0.05);且言语智商低于操作智商(P<0.05).在118例DMD患儿中有3例(2.5%)同时合并孤独症谱系障碍,CARS评分均≥30分.结论 DMD合并孤独症谱系障碍可能并不是偶然事件,DMD与孤独症谱系障碍可能存在一定联系.     

Duchenne型肌营养不良基因治疗研究进展

Duchenne型肌营养不良（DMD）是由编码抗肌萎缩蛋白的DMD基因突变导致的X连锁隐性遗传病。它的特点是进行性肌无力和因缺乏抗肌萎缩蛋白而导致的骨骼肌和心肌退化。患儿多于2~5岁起病,常在20岁左右死于心力衰竭或呼吸功能不全。目前,临床上多采用支持疗法改善疾病症状,但并不能改变疾病的最终结局。基因治疗的兴起为该病的治愈提供了希望。本文总结了DMD的基因替代疗法,包括腺相关病毒介导的DMD基因转导技术、肌营养不良蛋白相关蛋白（utrophin）上调技术和成簇规律间隔的短回文重复序列基因编辑技术的研究进展,并为解决腺相关病毒载量、转基因产物的长期有效表达、utrophin蛋白表达量问题提出的建议进行综述,为研究者们进一步研究提供参考。     

Intragenic deletions in the dystrophin gene in 211 Pakistani Duchenne muscular dystrophy patients

Background: Deletions of single or multiple exonic regions within the dystrophin gene can be detected using current molecular methods in approximately 65% of the patients with X‐linked recessive neuromuscular disorder, Duchenne/Becker muscular dystrophy (DMD/BMD). Population‐based variations in frequency and distribution of dystrophin gene deletions have been reported in DMD/BMD patients. In the present study, the first in the Pakistani population, frequency and distribution of deletions of 18 exons clustered in two hot spots within the dystrophin gene in 211 unrelated DMD patients were analyzed. Methods: A total of 211 patients suffering from DMD were ascertained, and intragenic deletions within the dystrophin gene were detected on polymerase chain reaction amplification of the genomic DNA using 18 primer sets clustered within two major deletion hot spots. lovd v.1.1.0 software from the Leiden Muscular Dystrophy website has been used to predict in‐frame and out‐of‐frame deletions. Results: Intragenic deletions were detected in 86 patients (40.75%): 35 patients (40.69%) had deletions within the proximal hot spot, and 51 patients (59.30%) had deletions confined to the distal deletion hot spot of the dystrophin gene. The most frequently deleted exons were 50, 6, 47, 13 and 52 with deletion frequencies of 15.11%, 12.79%, 10.46%, 8.13%, and 4.65%, respectively. lovd v.1.1.0 predicted out‐of‐frame deletions in 67 DMD patients and in‐frame deletions in 19 DMD patients. Conclusions: The observed proportion of intragenic deletions in the Pakistani population is relatively low, which is comparable with most of the Asian data. Also, deletions in 67 patients (77.9%) are in agreement with the frame‐shift rule.     

Pathogenesis of Duchenne muscular dystrophy: The calcium hypothesis revisited

Rapid advances in the molecular genetics of Duchenne muscular dystrophy (DMD) and the discovery and localization of the gene product dystrophin has brought new hope that successful treatment for this disease may not be too far away. Dystrophin has been postulated to have a mechanical function, helping to resist stress associated with muscle contraction. The presence of dystrophin in low concentrations in muscle cells, its expression in nervous tissue and the observation that hypercontraction of the sarcomeres precedes membrane rupture make the hypothesis unlikely. On the basis of an analogy with a cytoskeletal protein ankyrin, which is associated with the sodium/potassium adenosine triphosphatase (ATPase) in the kidney, it is possible that dystrophin deficiency leads initially to an increased but inefficient calcium-ATPase activity, which pumps calcium out of the cell. Partial failure of the pump would result in intracellular accumulation of calcium, hypercontractions of the sarcomeres, rupture of the cell membrane, massive influx of calcium and cell necrosis.     

Duchenne muscular dystrophy

Duchenne muscular dystrophy, an X‐linked disorder, has an incidence of one in 5000 boys and presents in early childhood with proximal muscle weakness. Untreated boys become wheelchair bound by the age of 12 years and die of cardiorespiratory complications in their late teens to early 20s. The use of corticosteroids, non‐invasive respiratory support, and active surveillance and management of associated complications have improved ambulation, function, quality of life and life expectancy. The clinical features, investigations and management of Duchenne muscular dystrophy are reviewed, as well as the latest in some of the novel therapies.     

Sleep disorders in boys with Duchenne muscular dystrophy

Aim: Determine the frequency and predictors of sleep disorders in boys with Duchenne Muscular Dystrophy (DMD). Method: Cross-sectional study by postal questionnaire. Sleep disturbances were assessed using the Sleep Disturbance Scale for Children (validated on 1157 healthy children). A total sleep score and six sleep disturbance factors representing the most common sleep disorders were computed. Potential associations between pathological scores and personal, medical and environmental factors were assessed. Results: Sixteen of 63 boys (25.4%) had a pathological total sleep score compared with 3% in the general population. The most prevalent sleep disorders were disorders of initiating and maintaining sleep (DIMS) 29.7%, sleep-related breathing disorders 15.6% and sleep hyperhydrosis 14.3%. On multivariate analysis, pathological total sleep scores were associated with the need to be moved by a carer (OR = 9.4; 95%CI: 2.2–40.7; p = 0.003) and being the child of a single-parent family (OR = 7.2; 95%CI: 1.5–35.1; p = 0.015) and DIMS with the need to be moved by a carer (OR = 18.0; 95%CI: 2.9–110.6; p = 0.002), steroid treatment (OR = 7.7; 95%CI: 1.4–44.0; p = 0.021) and being the child of a single-parent family (OR = 7.0; 95%CI: 1.3–38.4; p = 0.025). Conclusion: Sleep disturbances are frequent in boys with DMD and are strongly associated with immobility. Sleep should be systematically assessed in DMD to implement appropriate interventions.     

Autonomic function in patients with Duchenne muscular dystrophy

Background: Assessing autonomic function is important for patients with chronic heart failure, but the way that autonomic function changes in patients with Duchenne muscular dystrophy (DMD) and correlates with other clinical parameters during their young age is not clearly known. Methods: Heart rate variability (HRV) during ambulatory electrocardiogram (ECG) was performed in 57 DMD patients (130 recordings) who were not receiving medication (mean age 15.3 ± 4.5 years). The data were compared with the serum levels of brain natriuretic peptide (BNP), the shortening fraction (SF) of the left ventricle on echocardiography, and simple parameters of heart rate from 24 h ambulatory ECG. Results: Among four parameters of HRV measurements (high frequency [HF]; percentage of adjacent normal R‐R intervals that were >50 ms different for the entire 24 h recording [%RR50]; ratio of low to high frequency [LF/HF]; and standard deviation for all normal R‐R intervals for the entire 24 h recording [SDNN]), SDNN was most frequently abnormal. Even when SF was normal, a significant percentage of patients exhibited, abnormal parasympathetic activity (HF, %RR50: 74%, 78%, respectively), sympathetic activity (LF/HF, 43%), and SDNN (96%). Similarly, even if serum BNP levels were normal, 86%, 89%, 59%, and 97% of the patients displayed abnormal autonomic function on these measurements, respectively. Mean heart rate at night most accurately predicted abnormality of SDNN. When the cut‐off point for mean heart rate at night was 71 beats/min, the sensitivity and specificity of this parameter for predicting abnormal SDNN was 94% and 85%, respectively (P < 0.0001). Conclusion: In DMD, autonomic function, especially SDNN, was frequently abnormal, although conventional clinical examinations of cardiac function (BNP levels and SF) were normal. It is proposed that mean heart rate during night could be used as a simple measurement for evaluation of autonomic function.     

Deletion analysis for Duchenne (and Becker) muscular dystrophy

Abstract Forty-three unrelated South Australian boys diagnosed as having either Duchenne or Becker muscular dystrophy were screened for deletions using DNA probes to the dystrophin gene. For the 35 boys with Duchenne muscular dystrophy, the deletion frequency was 43% using a simplified probing strategy based on the probes Cf56a, Cf56b, pERT87-15 and XJ (XJ1.1 or XJ2.3). The corresponding deletion frequency for the eight boys with Becker muscular dystrophy was 38%. Members of families in which these disorders result from a deletion can now choose to prevent the birth of further affected boys, using an accurate prenatal test for the specific mutation occurring within the family. Deletion analysis also has the potential to clarify the carrier status of women in these families.     

Cardiomyopathy of Duchenne muscular dystrophy

Summary A total of 18 male patients with Duchenne muscular dystrophy (DMD), aged 8–29 years (mean, 15.7 years), were prospectively studied to assess the cardiomyopathy associated with DMD, using clinical parameters and noninvasive cardiovascular investigations: electrocardiogram (ECG), Holter monitoring, and echocardiography. In addition, five clinical tests of cardiovascular autonomic function were used to assess the role of the autonomic nervous system in the pathogenesis of dysrhythmias.The majority of subjects were asymptomatic, but four had abnormal physical findings. All had abnormal ECG, the commonest abnormality (in 16) being tall R waves or increased R/S ratios in the right precordial leads; 14 had abnormal findings on echocardiography, including three with poor left ventricular function and five with mitral valve prolapse (MVP). Labile abrupt sinus tachycardia was present in 11, and four had high-grade ventricular ectopy. None had definite clinical evidence of autonomic dysfunction.The cardiomyopathy of DMD appears to be unrelated to disease severity. However, abnormal Q waves or Q/R ratios in ECG leads I, a V_L, and V₅–V₆ are significantly related to young age (p<0.05), and high-grade ventricular ectopy occurred significantly more frequently (p<0.05) in older subjects (>15 years). Dysrhythmias were not related to the presence of MVP, poor left ventricular function, or autonomic dysfunction.     

杜氏肌营养不良与骨骼肌纤维化

骨骼肌纤维化是杜氏肌营养不良杜氏肌营养不良的主要病理变化之一,可影响肌纤维的再生、收缩功能,加重病情,在骨骼肌纤维化的发生发展过程中,炎症细胞、成纤维细胞、成肌纤维细胞及其分泌的细胞因子起重要作用.该文对杜氏肌营养不良的骨骼肌纤维化研究进展进行综述.