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.     

Whole-body vibration training in children with Duchenne muscular dystrophy and spinal muscular atrophy

IntroductionWhole-body-vibration training is used to improve muscle strength and function and might therefore constitute a potential supportive therapy for neuromuscular diseases.ObjectiveTo evaluate safety of whole-body vibration training in ambulatory children with Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA).Methods14 children with DMD and 8 with SMA underwent an 8-week vibration training programme on a Galileo MedM^® at home (3 × 3 min twice a day, 5 days a week). Primary outcome was safety of the training, assessed clinically and by measuring serum creatine kinase levels. Secondary outcome was efficacy as measured by changes in time function tests, muscle strength and angular degree of dorsiflexion of the ankles.ResultsAll children showed good clinical tolerance. In boys with DMD, creatine kinase increased by 56% after the first day of training and returned to baseline after 8 weeks of continuous whole-body vibration training. No changes in laboratory parameters were observed in children with SMA. Secondary outcomes showed mild, but not significant, improvements with the exception of the distance walked in the 6-min walking test in children with SMA, which rose from 371.3 m to 402.8 m (p < 0.01).InterpretationWhole-body vibration training is clinically well tolerated in children with DMD and SMA. The relevance of the temporary increase in creatine kinase in DMD during the first days of training is unclear, but it is not related to clinical symptoms or deterioration.     

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.     

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。     

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.     

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.     

Spontaneous deep venous thrombosis in Duchenne muscular dystrophy

Deep venous thrombosis (DVT) is an uncommonly encountered condition in childhood and, as a consequence, the diagnosis may be overlooked. We describe the first two cases of DVT occurring in children with Duchenne muscular dystrophy. Both brothers were wheel-chair-bound for protracted periods. The first case occurred following spinal fusion for scoliosis. The second occurred spontaneously following immobilisation in hospital while undergoing investigation for a ureteric stone. Serological investigations to outrule an underlying thrombogenic cause showed no deficiency of protein C or antithrombin III nor the presence of lupus anticoagulant in either patient. The presence of flaccid lower extremities resulting in prolonged immobilisation combined with an ineffective muscle pump for venous return may have predisposed the patients in our series. The issue of prophylaxis should now be actively considered in such patients in high-risk circumstances. Correspondence to: R. Fitzgerald     

假肥大型肌营养不良患者血清肌酸激酶变化规律

目的：假肥大型肌营养不良患者血清肌酸激酶随病程进展而不断变化。该研究旨在分析假肥大型肌营养不良患者血清肌酸激酶的变化规律。方法：收集临床已确诊的假肥大型肌营养不良患者的血清,其中男性39例,女性1例,通过连续监测法测定血清肌酸激酶。结果：假肥大型肌营养不良患者血清肌酸激酶在3～5岁达到峰值,以后随病程进展和年龄增加逐年下降,年均下降率为8.7%。结论：假肥大型肌营养不良患者的血清肌酸激酶在3～5岁达到峰值,以后随年龄增加而逐年下降,这种变化规律可以反映肌纤维坏死速率和病程进展速度,评估治疗效果。     

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.     

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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。     

Becker/Duchenne肌营养不良患儿临床表型与基因关联性预测分析

目的 探讨Becker/Duchenne肌营养不良（BMD/DMD）患儿的临床表型与基因型的关联性，为疾病的管理、基因治疗及产前诊断提供理论依据。方法 回顾性分析52例患儿的临床资料及基因检测结果，对52例患儿均采用多重连接探针扩增（MLPA）的方法检测DMD基因，对MLPA检测未发现基因异常的患儿采用外显子芯片捕获结合高通量测序技术（NGS）进行筛查；并对20例先证者的母亲进行了测序验证。结果 结合MLPA和NGS测序技术检测到50例患儿携带BMD/DMD致病基因，检出率为96%。其中，基因缺失36例（69%）、重复7例（13%）、微小突变7例（13%）。在43例存在基因缺失/重复的患儿中，DMD 32例，BMD 11例；37例（86%）符合阅读框架原则，其中DMD 27例（96%），BMD 10例（67%）。7例微小突变均为DMD。结论 阅读框架原则对DMD有极高预测价值，对BMD预测有限。     

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.     

6例杜氏肌营养不良回顾性分析

目的分析6例杜氏肌营养不良(DMD)患儿的临床特点,并结合文献复习,为早期诊断该病及采取有效治疗措施进行归纳总结。方法收集2010年1月至2015年10月收治的6例DMD患儿的临床资料,进行回顾性分析。结果 6例均为男性,确诊年龄1.2~11.5岁,均无家族史。起病隐匿,均有谷丙转氨酶、谷草转氨酶、乳酸脱氢酶、α-羟丁酸脱氢酶、肌酸激酶、肌酸激酶同工酶同步升高,以肌酸激酶升高最显著、为正常的3.7~107.2倍。基因检测均提示DMD基因突变;其中2例患儿的母亲行基因检测,提示携带相同突变基因。1例行肌肉活检,病理结果符合DMD改变。1例患儿行脐血间充质干细胞移植,5 d后肌酸激酶下降77.0%。结论对血清肌酶异常、运动功能异常的男童,应高度警惕DMD,尽早行CK及基因检测确诊,尽早干预,保护尚存的正常肌纤维,延缓疾病进展。     

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...     

Communication regarding breathing support options for youth with Duchenne muscular dystrophy

BACKGROUND:

Ventilators for home use, manual and mechanically assisted coughing techniques, and the services of in-home respiratory therapists are options for youth with Duchenne muscular dystrophy (DMD). Evidence supports the use of these modalities, but there seems to be few youth who are receiving these therapies. Is there a knowledge transfer issue? Is there a lack of resources? What is the best way to discuss the issues? What do youth and parents want?

OBJECTIVE:

To determine practices, attitudes and beliefs regarding the timing and content of client/family communication related to ventilatory support decisions for individuals with DMD.

METHODS:

A questionnaire was sent to all 19 children’s treatment centres in Ontario. The lead clinician responded on behalf of his or her centre. Another questionnaire was given to 11 families who attended a parent support meeting.

RESULTS:

Respondents from the treatment centres who provide services for youth with DMD indicated that there are resources in terms of personnel and an obligation to provide information about ventilatory support, but provision of information is often late and/or inconsistent. The family respondents wanted more information and they wanted it earlier than they are currently receiving it.

CONCLUSIONS:

Parents and youth dealing with DMD have many resources at their disposal in Ontario. The evidence is clear that there are long-term health benefits to providing ventilatory support as well as instruction in coughing assistance. Due to the classical nature of disease progression in DMD, information should be provided within reasonable timelines.     

肾病综合征合并Duchenne型肌营养不良症1例病例报告

【摘要】 目的 研究肾病综合征合并Duchenne型肌营养不良症患儿的临床特点,探讨肾病综合征与Duchenne型肌营养不良症的可能关系。方法 对2014年5月就诊于湖南省儿童医院肾内科的一例肾病综合征合并Duchenne型肌营养不良症患儿的临床特点、肾脏病理、基因诊断及对激素治疗的反应进行总结。结果 ①临床特点：6岁男孩,有1兄20岁,身体健康,家庭中两系3 代无类似疾病者。该患儿肾病综合征频繁复发,伴有谷草转氨酶、丙转氨酶、肌酸激酶、乳酸脱氢酶等肝酶及肌酶显著升高;肾脏病理为轻度系膜增生性肾小球肾炎。②遗传学检查：染色体核型分析无异常;dystrophy基因52号外显子缺失。结论 肾病综合征合并Duchenne型肌营养不良症患儿表现为难治性肾病,dystrophy基因52号外显子缺失与NS发病无直接联系,但有可能与NS频繁复发有关联,需要进一步研究。     

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.     

Feeding problems and weight gain in Duchenne muscular dystrophy

The aim of the study was to conduct a survey using a dedicated questionnaire to estimate feeding difficulties, gastrointestinal involvement and weight gain in a population of 118 Duchenne muscular dystrophy (DMD) patients (age range 13.80-35.8 years). All the answers were entered in a database and the data analysed subdividing the cohort into age groups (3-9, 9-13, 13-18, 18-24, 24-30, 30-36 years). The results indicate that chewing difficulties are frequent and become increasingly present with age, associated with a progressive increase of the duration of meals. Episodes of choking or other clinical signs of swallowing difficulties are in contrast much less frequent even after age 18. Aspiration pneumonia were also not very frequent and only occurred in 7/118. Clinical signs of gastroesophageal reflux requiring treatment were only found in 5 while 43/118 complained of constipation requiring treatment. Very few of our patients had their weight above 2 SD (n = 4) and this was always found in patients between 9 and 18 years while after this age there was an increasing number of patients with weight below 2 SD. The results of our survey suggest that although choking is one of the most feared complications in patients with DMD, clinical signs of swallowing abnormalities are infrequent when collecting clinical information retrospectively. Further studies using an objective evaluation such as videofluoroscopy are needed to identify minor signs that may not be obvious on clinical examination.