先天性肌病伴Ⅰ型肌纤维优势两例

非进行性先天性肌病是一组于出生或青少年时期发病的肌肉疾病。近年来新报告了多种非进行性先天性肌病,包括透明体肌病、肌质管肌病、Ⅰ型纤维优势等,但作为独立的疾病尚缺乏足够的病例数量和恒定的临床病理联系。本文报道两例经骨骼肌活检证实为先天性肌病伴Ⅰ型纤维优势。患儿分别为4岁半女孩和11岁男孩,均具有非进行性加重的肌无力症状、骨骼畸形等先天性肌病临床特点;体查发现患儿体形或脸型细长,漏斗胸或脊柱后突侧弯、高腭弓及翼状肩等骨骼畸形表现;二者的肌酸激酶皆正常,乳酸脱氢酶仅轻度增高;两例病例骨骼肌活检结果表现一致,除了ATPase染色显示Ⅰ型肌纤维数量超过了肌纤维总数的90%,并无其他特异性病理改变如中央轴空、肌管、中央核等特殊结构。     

LMNA 相关的先天性肌营养不良症1 例报告并文献复习

目的探讨LMNA相关的先天性肌营养不良症的临床特征和诊断。方法回顾1例LMNA基因突变引起的肌营养不良症病例的临床资料,并复习相关文献。结果患儿,女,8个月,临床表现为抬头乏力、眼睑下垂、运动发育迟缓。检测患儿及其父母、姐姐的LMNA基因,显示患儿存在杂合突变c.94-96 del AAG(p.K32del),确诊为LMNA突变引起的肌营养不良。患儿父母及姐姐均未发现LMNA基因突变。文献检索显示,LMNA相关的先天性肌营养不良症患儿80%以上以抬头乏力为主要表现,并且可能交叉重叠存在肢体近端肌无力、运动发育迟缓、轴向肌无力。结论 LMNA基因分析有助于早期诊断先天性肌营养不良。     

小梁纤维肌病临床病理研究

目的研究小梁纤维肌病(trabecularfibermyopathy,TFM)的临床和病理特征。方法回顾性分析9例TFM患者的临床资料,并结合文献对其病因、临床及病理特点进行分析。结果9例病例发病年龄2～37岁,平均19.7岁;男8例,女1例;主要表现为近端肌无力,症状较轻,进展缓慢,预后良好。其中2例临床诊断为面肩肱型肌营养不良,1例免疫组化染色证实为肢带型肌营养不良,余均未发现明确病因。结论TFM有其独特的病理改变和临床表现,可作为一种临床病理疾病名称,但是大部分病因不明。     

先天性糖基化障碍Ie 型合并先天性肌营养不良表型患儿临床和基因分析

目的探讨多萜醇磷酸甘露糖基转移酶1(DMP1)基因变异致先天性糖基化障碍Ie型(CDG-Ie)合并先天性肌营养不良表型的临床表现及基因变异。方法回顾分析1例CDG-Ie型合并先天性肌营养不良表型患儿的临床资料及基因检测结果。结果男性患儿,1月龄即发现头围小,随后有智力、运动发育迟缓、小头畸形、癫痫性脑病、肌力和肌张力减弱、双足挛缩、扁鼻梁、小下颌、双眼上斜、追光差等表现,血清肌酸肌酶升高。头颅磁共振示脑萎缩,脑外间隙弥漫性增宽,脑内髓鞘化明显偏弱。脑电图为暴发-抑制改变。基因测序显示患儿DPM1基因存在复合杂合变异,c.669-3CG和c.677GT;家系分析提示c.669-3CG来自母亲,c.677GT来自父亲。确诊为CDG-Ie。结论 CDG-Ie是CDG的罕见类型,常合并先天性肌营养不良表型,早期基因检测有助明确诊断。     

先天性巨结肠伴先天性巨结肠类缘病1例

肠神经元性发育异常（NID）是先天性巨结肠类缘病的一种,临床诊断困难,主要根据病理特征诊断。现就我科1例先天性巨结肠(HD)伴NID的病理改变报告如下。临床资料患儿,男,7 a,生后未排便,我院诊断为HD,生后52 d行横结肠肝曲造瘘。术后排便功能正常,9个月时行巨结肠根治术。病理报告：直肠壁肌间神经丛未见神经节细胞,吻合口肠壁神经丛内可见神经节细胞,个别节细胞呈空泡变性,诊断为HD（常见型）。术后3个月开始便秘,伴腹胀,洗肠无明显好转,反复发生肠炎和肠梗阻、水电解质紊乱、营养不良住院,肠镜下发现残留的升结肠及回…     

中央核肌病的临床与病理特点五例报告

目的 分析5例中央核肌病的临床及病理特点,探讨其诊断和鉴别诊断价值.方法 对5例肌肉活检证实的中央核肌病标本进行常规组织化学和酶组织化学染色,总结其临床及病理特点.结果 2～13岁发病,病程呈非进展或缓慢进展,肢带肌受累为主,近端重于远端,下肢重于上肢,肌萎缩不明显,腱反射减低,肌电图均为肌源性损害,血清肌酸激酶(CK)正常或轻度增高.2例为母子同时患病,母亲的另外一个儿子和女儿也有相似临床表现,考虑为常染色体显性遗传.肌活检病理可见5例均有中央核肌纤维比例增加(23%～93%)和选择性Ⅰ型纤维优势伴萎缩.2例还原型辅酶Ⅰ四氮唑还原酶染色见以中央核为中心的特征性轮辐状肌原纤维问网格结构,核周氧化酶活性增强,部分肌纤维可见核周空晕.结论 对幼儿或少年起病、病情缓慢进展、近端肢带肌无力为主、不能完成跑跳等爆发性动作且血清CK正常者,应该考虑良性先天性肌病的可能,肌活检病理发现中央核纤维比例明显增加以及Ⅰ型纤维优势伴萎缩可为中央核肌病的最后确诊提供重要的病理学依据.     

儿童型肌炎/皮肌炎临床和病理研究

目的　儿童型多发性肌炎 /皮肌炎 (JPM /DM)目前在国内外文献中的大宗病例报道不多。为深入探讨两病的特征 ,本文着重研究其临床及病理特点 ,以进一步认识两病。方法　回顾性分析 4 2例JPM/DM (2 4例JPM ,1 8例JDM )患儿的临床资料 ,总结其临床表现、血清肌酶学、肌电图、肌肉病理的特点。结果　该病临床上主要有肌无力、肌萎缩 ,CK等血清肌酶增高 ,肌电图主要呈肌源性损害。JDM大多还有典型的皮肤损害 ,部分病例可出现皮下钙质沉积。JPM/DM的肌肉病理均显示免疫炎性改变。JPM组肌内膜炎发生率较JDM组高 (70 .8%vs 38.9% ,P <0 .0 5 ) ,JDM组肌束周萎缩及血管病变的发生率较JPM组高 (72 .2 %vs 4 1 .7% ,94 .4 %vs 5 4 .2 % ,P <0 .0 5或 0 .0 1 )。结论　JPM和JDM的临床和病理有所不同 ,JPM的病理改变可表现为散在肌纤维变性坏死、肌内膜炎改变为主的特征 ,部分病例微血管病变较明显 ;而JDM组的典型病理为广泛微血管病变和肌束周萎缩     

先天性肌营养不良的诊断及层黏连蛋白表达的意义

目的 探讨先天性肌营养不良（CMD）的临床诊断、肌肉免疫组织化学特点及随访情况。方法 对8例CMD患儿的病例资料进行综合分析,并进行肌肉活检,利用抗层黏连蛋白以（laminin α2,又称merosin）、α抗肌萎缩相关糖蛋白（α-dystroglycan,α-DG）和β抗肌萎缩相关糖蛋白（β-dystroglycan,β-DG）抗体行肌肉活检组织免疫组织化学染色。结果 8例均于出生时或生后半年之内出现肌无力、肌张力低下,有的合并关节挛缩、喂养困难或呼吸功能不全。肌肉病理检查均发现肌营养不良改变特点。其中merosin染色阴性者4例,头颅MRI示脑白质髓鞘化不良;4例为merosin染色阳性,呈散发或常染色体隐性遗传,2例合并有智力低下,抗α-DG（1IH6）抗体染色显示α-DG糖基化低下,其中1例伴视神经萎缩,头颅MRI提示脑结构异常。结论 本组CMD中merosin染色既有阴性,也有阳性,merosin缺乏症（先天性肌营养不良1A型）更为常见,伴随脑白质病变。merosin染色阳性者中存在抗肌萎缩相关糖蛋白糖基化低下病例。     

儿童先天性均一性Ⅰ型肌纤维肌病伴臀肌挛缩症1例临床表现及病理特征

目的分析伴有臀肌挛缩症先天性均一性Ⅰ型肌纤维肌病1例患儿的临床及病理表现。方法选取伴有臀肌挛缩症的先天性均一性Ⅰ型肌纤维肌病1例。女,11岁。取其股四头肌标本,连续8μm冷冻切片,行苏木精-伊红(HE)、改良Gomori、过碘酸-Schiff(PAS)、油红-ORO、细胞色素C氧化酶(COX)、琥珀酸脱氢酶(SDH)和腺苷三磷酸环化酶(ATPase)组织化学染色;免疫组织化学染色包括慢肌肌球蛋白和快肌肌球蛋白抗体染色。光镜和电镜下观察其病理改变。结果HE染色可见轻度中心核,未见坏死和再生肌纤维;Comori染色未见杆状体、轴空或碎红肌纤维;整体肌纤维COX和SDH的活性减低;ATPase和荧光免疫组织化学染色均显示均一性Ⅰ型肌纤维占99%以上,Ⅱ型肌纤维严重缺乏低于1%。结论臀肌挛缩症可能被认为是先天性均一性Ⅰ型肌纤维肌病的临床表现之一。     

Merosin缺乏性先天性肌营养不良1A型1例报告

目的探讨LAMA2基因突变致先天性肌营养不良的临床特点及诊断方法。方法回顾分析1例merosin缺乏性先天性肌营养不良1A型(MDC1A)患儿的临床资料。结果患儿男性,2岁2个月首次就诊。临床表现为精神运动发育迟缓,不能站立、行走,口齿不清。肌酸激酶显著升高;头颅磁共振提示双侧脑室前角、后角周围及半卵圆中心深部白质呈长T1长T2、FLAIR序列大片高信号影。基因检测显示患儿有分别源自父亲的剪接突变(c.4718-1GA)、源自母亲的移码突变(c.4529delC),为复合杂合突变。查阅既往文献及数据库未见报道。根据ACMG指南,两种变异均判定为致病性变异,确诊为MDC1A。结论 MDC1A为LAMA2基因突变所致,肌肉活检及LAMA2基因检测可明确诊断。本次发现的基因突变为首次报道,扩充了先天性肌营养不良的基因突变谱。     

Minicores and congenital fibre type disproportion observed in a family

Objective: To report a family in which congenital fibre type disproportion (CFTD) and minicore disease have been observed in members of the same family, and raise the question of the relationship between CFTD and minicores.
Methodology: A follow-up clinical and biopsy study of a girl who presented to hospital because of marked hypotonia and non-progressive weakness. She had muscle biopsies at the age of 18 months and again at 4 1/2 years. Her asymptomatic parents were also biopsied. The muscle specimens were processed for histopathological and morphometric studies.
Results: The histopathological findings of the muscle of the daughter were consistent with CFTD. The muscle biopsy of her father was normal whereas her mother's revealed minicore formation.
Conclusions: The findings of CFTD and minicore disease in members of the same family suggest that CFTD and minicore formation may both be the result of a common pathological mechanism rather than each being a distinct clinicopathological entity.     

Congenital fibre type disproportion myopathy. A histological diagnosis with an uncertain clinical outlook.

Nine children with congenital fibre type disproportion (CFTD) are described. Their muscle biopsies contained type 1 fibres which were smaller than the largest type 2 fibres by at least 13.5%. Attention is drawn to the variable natural history of this disorder which generally carries a good prognosis but may sometimes be associated with fatal respiratory problems. For important therapeutic, genetic, and prognostic reasons CFTD must be distinguished from other conditions with similar histochemical or clinical features.     

Clinical variability of congenital myopathy with type I fiber atrophy: A long-term observation of three cases

The variable clinical courses of three cases of congenital fiber type disproportion (CFTD) over a period of 10 years are presented. All showed improvement in early childhood, but subsequently, varying degrees of deterioration were noted: specifically, marked deterioration in case 2 and decreased muscle strength in case 3. Maximal motor function levels were attained differently among the cases. Histological findings included type 1 fiber hypotrophy and increased internal nuclei in common in all cases. Fine structural changes, such as patchy areas of myofibrillar degeneration, were noted in cases 1 and 2 (second biopsy), and cytoplasmic bodies were seen in case 2 (second biopsy). Myotubes were noted in case 3. The degree of cyto-architectural changes did not correlate with clinical severity. The heterogeneity of CFTD is also discussed.     

Histopathological Study of the Biopsied Muscles from Juvenile Patients with Congenital Myotonic Dystrophy

Histopathology and histochemistry were studied in biopsied muscles from eight patients with the congenital form of myotonic dystrophy (congenital MyD) and one patient with the adult form (adult MyD). In the muscle pathology of the four patients aged between 5 and 11 years with congenital MyD, there was no immaturity of the fibers and the histological alterations were minimal. The pathological findings of the adult patient with congenital MyD resembled those of adult MyD. The immature condition of the musculature observed during the early infantile period, therefore, may once improve with motor development during childhood and, after that, the muscle fibers may degenerate in a similar manner to that seen in adult MyD. Two patients with marked talipes equinovarus displayed grouped atrophy. Small angular fibers and pyknotic nuclear clumps were observed in five patients. These findings suggest that some neurogenic factor might be involved in the muscular changes in this disorder.     

Neonatal hypotonias with congenital disproportion of various types of muscular fiber, especially type I fibers. Demonstration of the familial character of this new entity]

Two sisters presenting with benign congenital hypotonia are reported. In both cases the muscle biopsies demonstrated the same pathological pattern, consisting in an abnormal size disproportion between the two main cytoenzymological types of muscle fibers. Their father, exhibiting a slight and diffuse muscle weakness, showed a closely related histological aspect. These three cases bring the first evidence of a familial transmission of this new entity. Its relationship with the other types of "congenital myopathies" is discussed.     

Kongenitale Muskeldystrophie

Zusammenfassung Es wird über vier Kinder mit kongenitaler Muskeldystrophie berichtet. Alle Patienten boten bereits bei der Geburt das typische klinische Bild mit Schwäche und Hypotonie einer mangelhaft angelegten Muskulatur. Die Diagnose wurde histologisch gesichert. Dabei waren Veränderungen zu beobachten, die dem Endstadium der progressiven Muskeldystrophie entsprechen: Atrophierte und (pseudo)hypotrophierte Muskelfasern mit deutlichen Kaliberschwankungen; Vermehrung des peri- und endomysialen Bindegewebes sowie interstitielle Makrophagenaktivierung.Bei einer Patientin (B. H.) war der Nachweis eines IgG-Paraproteins bemerkenswert; ein solcher Befund ist bisher nicht beschrieben worden.

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Congenital muscular dystrophy

Four cases of congenital muscular dystrophy are reported. All patients presented a clinical picture which was characterized by muscular weakness and hypotonia already manifest at birth. The diagnosis was confirmed by a muscle biopsy. The histological findings were similar to those observed in the final stage of progressive muscular dystrophy: Atrophic and (pseudo) hypertrophic fibres with great variations in size, an increase of perimysial and endomysial connective tissue, and an interstitial activation of macrophages.In one case (B. H.) an IgG-paraproteinemia was found which seems remarkable; similar observations in combination with muscular dystrophy have not yet been described in the literature.

Herrn Professor Dr. K. H. Schäfer zum 60. Geburtstag     

A Case of Congenital Myopathy without Specific Features

We report a 4-year-6-month-old boy with congenital myopathy without specific features. He showed delayed motor milestones, gaining head control at four months, and walking without support at one year six months. He was not a floppy infant after birth. Physical examination disclosed a myopathic face and muscle atrophy, predominantly in the proximal muscles, particularly in the scapular and pelvic girdles. A proximal muscle biopsy showed a mild variation in fiber size without any specific structural abnormality. Fiber type analysis showed type 2B fiber smallness. We compare our case with previously reported cases of minimal change myopathy (congenital myopathy without specific features).     

Vascular Abnormalities in Congenital Cutis Laxa - Report of Two Cases-

Two cases of Japanese girls with congenital cutis laxa associated with cardiovascular abnormalities are described. Case 1: A 12-year-old girl has been under our observation from the age of 6 months. Cardioangiogram revealed dilatation of the ascending aorta, meandering of the descending aorta and the coronary arteries, coiling of the carotid and innominate (brachiocephalic) arteries, and hypoplasia of the pulmonary arteries. Case 2: A 2.8/12-year-old girl died after our follow-up from the age of 3 months. The cause of death was congestive heart failure secondary to peripheral stenosis of the pulmonary arteries. In both cases, skin biopsy revealed a decreased number of elastic fibers and an increased amount of acidic mucopolysaccharides. The same histological features were observed in the pulmonary arteries and other arteries as well. Electron microscopic findings were diffuse thinning of elastic fibers and reduced elastic content. The high blood level of elastase (167.8 μg/l) in case 1 may cast a light on the unknown etiology of the disease.     

Progressive Muscular Dystrophy with Particular Reference to Muscle Regeneration

In various progressive muscular dystrophies (PMD), there were a number of fibers with histological and histochemical characteristics of regenerating fibers. With a morphometric analysis in diseased muscles, an identification of type 2C fiber on ATPase stain was the most simple and reliable method for fiber type evaluation. The type 2C fiber comprised 16.5% in Duchenne and 27.5% in Fukuyama type congenital MD, suggesting an active regenerating process taking place in both diseases. Regenerative capacity of muscle fibers after experimental damage to dystrophic chicken and mdx mouse muscles was similar to those seen in nondystrophic control muscles. From the above results, we speculate that a certain environmental factor such as interstitial fibrosis seems to play a major role in delaying regeneration in dystrophic muscles.