强直性肌营养不良3个家系26例患者白内障发病的特征

背景:白内障并不是强直性肌营养不良必须症状,但它可以是强直性肌营养不良患者早期甚至惟一的临床体征,分子诊断可作为强直性肌营养不良的诊断提供重要依据。目的:分析上海松江地区强直性肌营养不良3个家系26例患者与白内障发病的特征。设计:家系系谱分析。单位:解放军第二军医大学长海医院神经内科。对象:选择2001-05/2003-08在解放军第二军医大学长海医院神经内科收治的3个强直性肌营养不良家系共26例初步诊断或可疑强直性肌营养不良患者为观察对象,年龄7～71岁,其中13例患者均符合《实用神经病学》拟定的临床诊断标准。另13例有部分或轻度强直性肌营养不良症状与(或)体征,为可疑强直性肌营养不良患者。方法:①分别对受检者抽取1mL静脉血按常规法提取DNA,根据强直性肌营养不良的分子诊断标准(CTG三核苷酸重复数80～3350次),长模板扩增PCR法检测CTG重复数。②采用裂隙灯检查患者晶状体观察白内障发病情况,并分析强直性肌营养不良与白内障发病的关系。主要观察指标:①CTG重复数。②强直性肌营养不良患者与白内障发病的关系。结果:26例患者中,除1例为不孕症患者被排除,其余25例患者均进入结果分析。①受检者中25例患者符合强直性肌营养不良的分子诊断标准(CTG三核苷酸重复数80～3350次)。另1个体CTG重复数为13次,临床为不孕症患者,属正常个体。17例白内障患者CTG重复数平均为(2380±80)次,而8例无白内障的强直性肌营养不良患者其CTG重复数平均为(2298±105)次,两者间比较差异无显著性意义(P>0.05)。②17例白内障患者主要表现为晶状体呈彩虹色浑浊或后极部皮质蓝色浑浊。其中8例患者白内障为强直性肌营养不良惟一的早期表现,其CTG重复数均高于正常值。结论:强直性肌营养不良家系中,当特征性的白内障作为强直性肌营养不良患者主要甚至惟一的临床体征时,将为强直性肌营养不良的早期诊断提供重要临床依据。     

强直性肌营养不良的临床及病理研究

目的　通过对强直性肌营养不良的临床表现及肌肉病理研究 ,总结该病的临床及病理特点 ,加深对其的认识以提高诊断水平。方法　对两例强直性肌营养不良病人分别进行肌电图、肌肉活检、头颅磁共振成像、血清酶、血生化等项检查。结果　两例病人均呈慢性病程 ,以肌无力、肌萎缩为主要表现 ,伴有头发稀疏、白内障、心脏传导阻滞等多系统损害。临床无肌强直表现 ,但通过肌电图检查均发现有自发强直电位发放。肌活检均以肌纤维核内移、核袋及核链现象为主要病理改变。结论　强直性肌营养不良是一少见疾病 ,是以肌无力、肌强直为主要表现的多系统损害的遗传性疾病。肌强直症状不突出时 ,易延误诊断。尽早行肌电图检查以发现亚临床肌强直现象 ,并进行肌活检是诊断该病的关键。     

强直性肌营养不良2例

强直性肌营养不良是以肌强直和进行性肌无力、萎缩为特征的常染色体显性遗传病，临床上本病比较少见，现结合文献报告2例如下。     

一个强直性肌营养不良1型家系的临床、遗传学特点分析

目的:探讨强直性肌营养不良1型(DM1)一家系的临床和遗传学特点。方法:调查部分家系成员,并行体格检查及心电图、肌电图、血生化等检查和DM1致病基因强直性肌营养不良蛋白激酶(DMPK)基因的检测,绘制家族系谱图。结果:共发现6例患者,其中4例DMPK基因CTG三核苷酸扩增次数超50次,肌电图见肌强直电位发放;家系患者发病年龄逐代提前,家族中因此出现不同发病类型的患者。6例患者中明确合并早秃的有4例,智力减退4例,心脏传导阻滞4例,甘油三酯明显升高2例,白内障1例。结论:同一家系的DM1患者的临床表现可差异较大,接诊时应注意排查家族中的亚临床或轻型患者。DM1是一种多系统损害的遗传性疾病,可合并智力障碍和高甘油三酯血症。     

强直性肌营养不良97例临床资料分析

目的了解强直性肌营养不良的临床特点,提高临床诊断的准确性.方法借鉴循证医学系统评价方法,对四川大学华西医院神经内科1990～2000年间出院诊断为强直性肌营养不良的住院病例资料及1980～1999年国内文献报告的临床病例资料进行综合分析. 结果共收集到97例病例资料,其中94例来自国内文献报告,3例来自四川大学华西医院病历记录.该97例中,男性64例,女性33例,平均发病年龄28.5岁.90%的病例有家族史.常见症状依次为肌强直(99%),肌无力(97%),肌萎缩(85%),白内障(63%),脱发或秃顶(57%),性腺萎缩(37%),性欲障碍(33%),心脏损害(11%),智力减退(11%),甲状腺和肾上腺功能低下(8%)和精神发育缺陷(8%).结论强直性肌营养不良除肌强直、肌无力、肌萎缩最常见外,尚伴有白内障、脱发、秃顶、性腺萎缩等多系统损害,其临床表现复杂多样,阳性家族史对该病的诊断很有帮助,需加强认识,以提高临床诊断率.     

伴脑白质病变的强直性肌营养不良症两例

本研究经秦皇岛市第一医院伦理委员会批准,免除受试者知情同意,批文编号:2021L001. 病例1:患者男,14岁,间断四肢抽搐1年,每次数秒缓解.于2019年4月23日来秦皇岛市第一医院就诊.查体:双肺叩清,未闻及干湿性啰音.颅脑MRI示双侧额、顶、颞叶、侧脑室旁白质可见片状异常信号影,T1WI呈低信号,T2WI呈高信...     

进行性肌营养不良1例家系调查

对1例家系中有进行性肌营养不良患者的姐妹进行遗传优生咨询并家系调查,报告如下。     

强直性肌营养不良一例

患者男,48岁,因"四肢无力8年,加重1年"入院.入院前8年患者无明显诱因双手力弱,以左手明显,连续上举哑铃仅能完成6个.握拳后不能立即将手伸直、松开手,强直以拇指为重.遇冷加重.双下肢无力见于行走时,略微行走即有酸胀感,休息后可缓解.上楼困难,下楼尚可.言语含混不清.5年来无力渐加重.1年前上述不适明显加重,双手不能持重.双手指端麻木.     

强直性肌营养不良中枢神经系统损害1例

患者，男，39岁。因双手初始动作困难19年，无力、肌萎缩5年，双足无力2年，于2005年4月29日入院。查体：意识清楚，秃顶，鹅颈，心界向左下扩大。近记忆力、计算力差，时间地点定向力正常。轻度构音障碍，有时说话发第1声困难。双手握拳后不能立即松开，行走时起步困难，突然停下易摔跤。握拳、伸腕，伸趾，双踝背屈肌力4肌。四肢近端肌力5级，双侧颞肌、胸锁乳突肌、双手大小鱼际肌、骨间肌萎缩。扣击双前臂及舌部可见肌丘现象。肌张力正常。     

强直性肌营养不良症16例临床分析及文献复习

目的:通过对强直性肌营养不良(DM)16例患者临床资料综合分析,总结其临床特点,结合文献,提高对该病诊断和治疗水平。方法:收集16例DM患者病例资料,采用描述性统计对本组患者临床表现、实验室检查、肌活检病理、电生理及基因测序结果进行分析,总结其临床特征及治疗方法。结果:本组资料肌肉强直发生率50%,萎缩和无力发生率100%;心脏受累发生率81.25%,其中以房室传导阻滞25%最常见,心脏结构异常发生率31.25%。肌电图表现为强直电位伴或不伴肌源性损害93.75%;肌肉活检HE染色示肌纤维大小明显不等,内核纤维明显增多,可见数条多核袋纤维。完善基因检查7例,均提示DMPK基因的3’UTR区的CTG重复数目,超过50次。结论:DM患者临床表型复杂,易漏诊、误诊,早期识别不典型临床症状意义重大。对于确诊的DM患者,长程的对于骨骼肌外症状尤其是心肺功能管理极为重要。     

Chronic pain in persons with myotonic dystrophy and facioscapulohumeral dystrophy

Jensen MP, Hoffman AJ, Stoelb BL, Abresch RT, Carter GT, McDonald CM. Chronic pain in persons with myotonic dystrophy and facioscapulohumeral dystrophy.

Objective

To determine the nature and scope of pain in working-aged adults with myotonic muscular dystrophy (MMD) and facioscapulohumeral muscular dystrophy (FSHD).

Design

Retrospective, cross-sectional survey.

Setting

Community-based survey.

Participants

Convenience sample of subjects with MMD and FSHD.

Interventions

Not applicable.

Main Outcome Measures

Overall intensity and duration of pain, pain inference, pain sites, pain treatments, and relief provided by pain treatments.

Results

More subjects with FSHD (82%) than with MMD (64%) reported pain. The most frequently reported pain sites for both diagnostic groups were lower back (66% MMD, 74% FSHD) and legs (60% MMD, 72% FSHD). Significant differences in pain intensity were found between the diagnostic groups in the hands, legs, knees, ankles, and feet, with patients with MMD reporting greater pain intensity at these sites than patients with FSHD. Age was related to the onset of pain (participants reporting pain were younger than those not reporting pain in the FSHD sample), but pain severity was not significantly associated with age in those reporting pain. Respondents with both diagnoses that reported mobility limitations and used assistive devices (eg, wheelchair, cane) reported more pain severity than those with mobility limitations who did not use assistive devices, who, in turn, reported more pain severity than respondents who reported no mobility limitations at all. The treatments that were reported to provide the greatest pain relief were not necessarily those that were the most frequently tried or still used.

Conclusions

The findings indicate that pain is a more common problem in persons with FSHD than in persons with MMD, although it is common in both populations. In addition, these pain problems are chronic, underscoring the need to identify and provide effective pain treatments for patients with these neuromuscular diseases.     

Respiratory failure and cardiac disturbances in myotonic dystrophy

Cardiopulmonary abnormalities are frequently encountered in myotonic dystrophy. We present five patients with myotonic dystrophy who entered the intensive care unit in acute respiratory failure. The possible etiologic factors of pulmonary complications are reviewed. The most important is probably aspiration pneumonia. The difficulties in the treatment of the respiratory failure are emphasized. Myotonia of the chest muscles and diaphragm make artificial ventilation difficult. Recovery is delayed chiefly by swallowing disturbances. General anaesthesia is hazardous. Four patients presented cardiac arrhythmias and/or conduction abnormalities which were transient.     

Defining the performance parameters of a rapid screening tool for myotonic dystrophy type 1 based on triplet-primed PCR and melt curve analysis

Background: DMPK CTG-repeat expansions that cause myotonic dystrophy type 1 (DM1) can be detected more rapidly, cost-effectively, and simply by combining triplet-primed PCR (TP-PCR) with melting curve analysis (MCA). We undertook a detailed technical validation study to define the optimal operational parameters for performing bidirectional TP-PCR MCA assays.

Methods: We determined the assays’ analytic specificity and sensitivity, assessed the effect of reaction volumes, DNA diluents, and common contaminants on melt peak temperature, determined the assays’ sensitivity in detecting low-level mosaicism for repeat expansion, and evaluated their performance on two real-time PCR platforms.

Results: Both assays were highly specific and sensitive, and performed optimally under a broad range of parameters. Bidirectional TP-PCR MCA analysis also reduces the risk of generating false-negative results associated with the rare CCG-interruptions that may be present at either end of expanded alleles.

Conclusion: The DMPK TP-PCR MCA is a highly specific, sensitive, and significantly cost-saving screening tool for DM1.     

Myocardial fibrosis in patients with myotonic dystrophy type 1: a cardiovascular magnetic resonance study

Background

Myotonic dystrophy type 1 (DM1) is associated with increased cardiac morbidity and mortality. Therefore, assessment of cardiac involvement and risk stratification for sudden cardiac death is crucial. Nevertheless, optimal screening-procedures are not clearly defined. ECG, echocardiography and Holter-monitoring are useful but insufficient. Cardiovascular magnetic resonance (CMR) can provide additional information of which myocardial fibrosis may be relevant.The purpose of this study was to describe the prevalence of myocardial fibrosis in patients with DM1 assessed by CMR, and the association between myocardial fibrosis and abnormal findings on ECG, Holter-monitoring and echocardiography.

Methods

We selected 30 unrelated patients with DM1: 18 patients (10 men, mean age 51 years) with, and 12 patients (7 men, mean age 41 years) without abnormal findings on ECG and Holter-monitoring.Patients were evaluated with medical history, physical examination, ECG, Holter-monitoring, echocardiography and CMR.

Results

Myocardial fibrosis was found in 12/30 (40%, 9 men). The presence of myocardial fibrosis was associated with the following CMR-parameters: increased left ventricular mass (median (range) 55 g/m² (43–83) vs. 46 g/m² (36–64), p = 0.02), increased left atrial volume (median (range) 52 ml/m² (36–87) vs. 46 ml/m² (35–69), p = 0.04) and a trend toward lower LVEF (median (range) 63% (38–71) vs. 66% (60–80), p = 0.06). Overall, we found no association between the presence of myocardial fibrosis and abnormal findings on: ECG (p = 0.71), Holter-monitoring (p = 0.27) or echocardiographic measurements of left ventricular volumes, ejection fraction or global longitudinal strain (p = 0.18).

Conclusion

Patients with DM1 had a high prevalence of myocardial fibrosis which was not predicted by ECG, Holter-monitoring or echocardiography. CMR add additional information to current standard cardiac assessment and may prove to be a clinically valuable tool for risk stratification in DM1.     

Structural and functional cardiac changes in myotonic dystrophy type 1: a cardiovascular magnetic resonance study

Background

Myotonic dystrophy type 1 (MD1) is a neuromuscular disorder with potential involvement of the heart and increased risk of sudden death. Considering the importance of cardiomyopathy as a predictor of prognosis, we aimed to systematically evaluate and describe structural and functional cardiac alterations in patients with MD1.

Methods

Eighty MD1 patients underwent physical examination, electrocardiography (ECG), echocardiography and cardiovascular magnetic resonance (CMR). Blood samples were taken for determination of NT-proBNP plasma levels and CTG repeat length.

Results

Functional and structural abnormalities were detected in 35 patients (44%). Left ventricular systolic dysfunction was found in 20 cases, left ventricular dilatation in 7 patients, and left ventricular hypertrophy in 6 patients. Myocardial fibrosis was seen in 10 patients (12.5%). In general, patients had low left ventricular mass indexes. Right ventricular involvement was uncommon and only seen together with left ventricular abnormalities. Functional or structural cardiac involvement was associated with age (p = 0.04), male gender (p < 0.001) and abnormal ECG (p < 0.001). Disease duration, CTG repeat length, severity of neuromuscular symptoms and NT-proBNP level did not predict the presence of myocardial abnormalities.

Conclusions

CMR can be useful to detect early structural and functional myocardial abnormalities in patients with MD1. Myocardial involvement is strongly associated with conduction abnormalities, but a normal ECG does not exclude myocardial alterations. These findings lend support to the hypothesis that MD1 patients have a complex cardiac phenotype, including both myocardial and conduction system alteration.     

Identification of key genes in allergic rhinitis by bioinformatics analysis

ObjectiveThis study aimed to explore the potential molecular mechanism of allergic rhinitis (AR) and identify gene signatures by analyzing microarray data using bioinformatics methods.MethodsThe dataset {"type":"entrez-geo","attrs":{"text":"GSE19187","term_id":"19187"}}GSE19187 was used to screen differentially expressed genes (DEGs) between samples from patients with AR and healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied for the DEGs. Subsequently, a protein–protein interaction (PPI) network was constructed to identify hub genes. {"type":"entrez-geo","attrs":{"text":"GSE44037","term_id":"44037"}}GSE44037 and {"type":"entrez-geo","attrs":{"text":"GSE43523","term_id":"43523"}}GSE43523 datasets were screened to validate critical genes.ResultsA total of 156 DEGs were identified. GO analysis verified that the DEGs were enriched in antigen processing and presentation, the immune response, and antigen binding. KEGG analysis demonstrated that the DEGs were enriched in Staphylococcus aureus infection, rheumatoid arthritis, and allograft rejection. PPI network and module analysis predicted seven hub genes, of which six (CD44, HLA-DPA1, HLA-DRB1, HLA-DRB5, MUC5B, and CD274) were identified in the validation dataset.ConclusionsOur findings suggest that hub genes play important roles in the development of AR.