Progressive Muscular Dystrophy in Infancy

Clinical features of 11 cases of muscular dystrophy in infancy were discussed. From the detailed symptomatological analysis of the 11 patients we reported here, we found two subgroups of infantile muscular dystrophy. There were 6 cases of congenital cerebro-muscular dystrophy (Fukuyama) and 5 cases characterized by comparatively late onset, no sexual preference, proximally dominant muscle wasting, infrequence of associated joint contractures, normal facial muscle and no mental deficiency. The characteristics of this latter group in infantile muscular dystrophy are similar to those of limb-girdle muscular dystrophy. It is suggested that some of the patients with limb-girdle type of muscular dystrophy may have its onset in infancy.     

结缔组织生长因子在进行性肌营养不良中的表达

目的探讨结缔组织生长因子（CTGF）在进行性肌营养不良（PMD）中的作用。方法使用Duchenne型肌营养不良（DMD）8例、Becker型肌营养不良（BMD）2例、先天性肌营养不良（CMD）6例患儿的肌肉活检标本,借助免疫组织化学、双免疫荧光方法及Western印迹分析检测CTGF的免疫表达和定位。结果免疫组织化学和双免疫荧光法显示CTGF在正常肌肉的血管处明显表达;免疫组织化学法和Western印记分析均显示在PMD的萎缩肌肉中CTGF的免疫反应明显增强,所有病变肌肉组织中,CTGF在再生纤维的膜、胞浆及胞核中、巨噬细胞及巨噬细胞浸润的坏死纤维中强烈表达,也免疫定位在非再生纤维的肌纤维膜、肌内膜及肌束膜的结缔组织中;双免疫标记显示在肌内膜及肌束膜的大多数激活的成纤维细胞表达CTGF;但年长的CMD患儿的晚期纤维化中CTGF弱表达或无表达。结论结果表明CTGF可能参与了PMD的发病过程,肌肉内的CTGF可能在肌纤维再生和肌肉纤维化的病变过程中起重要作用。     

进行性肌营养不良患儿肌肉组织转化生长因子-β_1的表达

目的　进行性肌营养不良肌纤维化的病理机制不清。转化生长因子 β1(TGF β1)能诱导细胞外基质的积聚 ,对纤维发生和组织修复起调节作用。本研究探讨进行性肌营养不良患儿肌肉TGF β1表达与肌纤维化的关系 ,阐明儿童进行性肌营养不良肌纤维化慢性病理进展的部分机制。方法　采用免疫荧光和免疫印迹的方法检测 18例进行性肌营养不良患儿 [7例Duchenne肌营养不良 (DMD) ,6例福山型和 3例非福山型先天性肌营养不良 (FCMD ,nFCMD) ,2例Becker型肌营养不良 (BMD) ]和 13例非神经肌肉疾病患者肌肉组织中TGF β1表达。结果　先天性肌营养不良 (CMD)和DMD肌组织内潜伏和活性形式的TGF β1均免疫定位于肌纤维和间质的肌内膜 ,表达强度以CMD为著。免疫印迹结果显示FCMD肌肉组织TGF β1表达强于DMD和对照。结论　在儿童进行性肌营养不良的肌肉慢性病理进展中 ,肌肉纤维化可能是重要原因之一。     

Antinuclear factor, smooth and striated muscle antibodies in Duchenne-type muscular dystrophy

Antinuclear factors and antibodies to smooth and striated muscle were studied by the indirect immune fluorescence method in the sera of 19 children suffering from progressive muscular dystrophy. In 47% of the patients antinuclear factor positivity, in 65% anti smooth muscle antibody positivity, and in 26% antistriated muscle antibody positivity was found. Antibody to striated muscle was present in patients with serious advanced dystrophy and in patients unable to walk, while anti-smooth muscle antibody occurred in less serious cases, too. On the basis of the results, it is concluded that in genetically determined progressive muscular dystrophy a secondary autoimmune process develops owing to the degeneration of muscles as the disease progresses.     

基质金属蛋白酶-1与基质金属蛋白酶抑制剂-1在纤维性肌性斜颈患儿中的表达

目的探讨基质金属蛋白酶-1(MMP-1)和基质金属蛋白酶抑制剂-1(TIMP-1)在先天性纤维型肌性斜颈胸锁乳突肌的表达。方法采用Masson三色胶原染色法观察先天性肌性斜颈患儿胶原的增生情况,并进行肌肉型和纤维型分组,获得纤维型标本22例,应用免疫组织化学染色法观察MMP-1、TIMP-1在纤维型组中的表达情况,并与6例对照组比较。结果免疫组织化学染色显示,MMP-1在先天性纤维型肌性斜颈胸锁乳突肌患儿明显减少,与对照组比较有显著性差异(P<0.01);先天性纤维型肌性斜颈胸锁乳突肌患儿TIMP-1表达与对照组比较无显著性差异(P>0.05)。结论先天性肌性斜颈胸锁乳突肌的纤维化与MMP-1减少有关。     

Hand and ECG tremor in spinal muscular atrophy.

The presence of hand and electrocardiogram (ECG) tremor was studied in 31 children with severe, intermediate, or mild form of spinal muscular atrophy. Clinical tremor of the hands was seen in 16 (59%) of 27 patients, all with benign forms of the disease. Nineteen patients had ECG tremors, of whom 17 had the mild or intermediate form. With the exception of one, all patients in the mild or intermediate group had hand or ECG tremor. Hand and ECG tremor are valuable in the diagnosis of the benign forms of spinal muscular atrophy; they are of no value in diagnosis of the severe infantile type.     

肌营养不良冷冻肌肉标本纤溶酶原激活物抑制物-1的表达

目的探讨纤溶酶原激活物抑制物-1(PAI-1)借助于抑制细胞外基质降解在进行性肌纤维化的发展中作用,揭示PAI-1在肌营养不良(MD)中的作用。方法应用免疫组织化学、双免疫荧光标记和Western印迹分析检测5例Duchenne型肌营养不良(DMD)、3例Becker型肌营养不良(BMD)、9例先天性肌营养不良(CMD)和4例正常活检冷冻肌肉标本中PAI-1的表达和细胞定位。结果PAI-1只在正常肌肉的血管内皮细胞处表达。免疫组织化学及Western印迹分析均表明PAI-1在大多数MD的萎缩肌肉中的表达明显高于正常肌肉。双免疫标记显示PAI-1在再生肌纤维的细胞浆和细胞核、巨噬细胞、巨噬细胞浸润的坏死纤维中强烈表达,在DMD和CMD肌肉中的肌内膜和肌束膜中的某些激活的成纤维细胞中明显表达。结论PAI-1在萎缩肌肉中过度表达的作用尚不清楚,但PAI-1在MD病变肌肉的局部表达增强及其明显的分布类型为PAI-1参与MD的病变提供了依据。     

儿童脊肌萎缩症23例临床特点及遗传学分析

目的 探讨脊肌萎缩症的临床特点和遗传方式。方法 对23例脊肌萎缩症患儿的临床资料进行总结,并用Weiber先证法分析其发病的遗传规律。结果 临床特点为出生后双下肢呈对称性弛缓性瘫痪且进行性加重,四肢近端无力,肌张力、肌力低下;肌电图主要表现为神经原性损害。隐性遗传分离分析表明,12个家系23例患儿发病方式符合常染色体隐性遗传。结论 脊肌萎缩症的临床发病早且病死率高,在遗传咨询中注意作相关产前基因检查,可避免该类患儿的出生。     

Congenital muscular torticollis: current concepts and review of treatment

PURPOSE OF REVIEW: The purpose of this review is to better understand the spectrum of disease in torticollis, which is the third most common pediatric orthopaedic diagnosis in childhood. Besides the benign muscular tightness of the sternocleidomastoid muscle leading to the classic head position, the differential diagnosis of the wry neck include sequelae to inflammatory, ocular, neurologic or orthopedic diseases. Patients present with a stiff and tilted neck, and therefore require a thorough and systematic work-up, including a complete physical and neurologic examination and cervical spine radiographs. RECENT FINDINGS: Recent findings show that magnetic resonance imaging of the brain and neck is no longer considered cost-effective, or necessary, in congenital muscular torticollis. Observation and physical therapy, with or without bracing, is usually an effective treatment in most cases, especially if instituted within the first year of life. Botox has recently been shown to be an effective intermediate method of treatment for more resistant cases of congenital muscular torticollis. In those presenting after the age of 1 year, there is an increased rate of sternocleidomastoid muscle lengthening. The lengthening may improve the range of motion, but not necessarily the plagiocephaly, facial asymmetry, or cranial molding. SUMMARY: It is important to differentiate muscular from nonmuscular torticollis. Congenital muscular torticollis is benign; missing a case of nonmuscular torticollis could be potentially life threatening.     

Congenital muscular dystrophy

We report the cases of 18 patients with congenital muscular dystrophy, six of whom also have involvement of the central nervous system, corresponding to the Fukuyama type of congenital muscular dystrophy. In four patients, both the central nervous system and the eyes are involved, and the diagnosis of "muscle, eye and brain disease" was made. A comparative study of these patients with those whose cases were recently reported indicates that there is a wide variability of clinical and laboratory expression of the dystrophy, but a constant feature in all patients is a progression of motor disability. The association of congenital muscular dystrophy with brain abnormalities indicates a poor clinical prognosis. At present it remains an open question whether the three variants of the disease are separate diseases or only different expressions of the same syndrome, but our study tends to support the latter hypothesis.     

Familial congenital muscular dystrophy caused by phosphofructokinase deficiency]

Two children, born to related parents, presented since birth a muscular defect rapidly complicated by painful joint stiffness. The oldest child died at 6 months of age, from respiratory complications. The second-14 month old- does not sit without support. The muscle fibres are of unequal calibre and numerous fibres have under-sarcolemmal PAS positive areas contain glycogen, as seen on electron microscopy. In the second patient, the biochemical analysis showed a moderate glycogen accumulation and muscular enzymatic studies demonstrated an isolated and major deficiency in phosphofructokinase activity. Activity was normal in red blood cells and in fibroblasts cultured in vitro. Hence, these cases should be distinguished from formerly reported cases of phosphofructokinase deficiency. This type of P.F.K. deficiency should be looked for in patients with severe congenital muscular dystrophy and early joint involvement.     

Juvenile acid maltase deficiency presenting as paravertebral pseudotumour

In addition to the infantile lethal form of glycogen storage disease with cardiomyopathy (GSD Type IIa, Pompe disease) 1,4 glucosidase or acid maltase deficiency has been reported in a few children and adults (GSD Type IIb or IIc) erroneously thought to have muscular dystrophies. The clinical heterogeneity of the muscle involvement in these latter cases is illustrated in a 12-year-old boy presenting with a right lumbar mass, growth retardation, muscular weakness including difficulty in walking, and marked elevations of muscle and liver enzymes. Light-and electron-microscopic examination of specimens from the lumbar mass, apparently normal skeletal muscle and liver, showed typical changes consistent with the biochemical and enzymatic features of acid maltase deficiency. GSD Type IIb and IIc are more frequent than suspected, may present as local pseudohypertrophy and should be considered in patients with progressive muscle disease and abnormal serum enzymes.Abbreviations GSD glycogen storage disease - SGOT serum glutamic oxaloacetic transaminase - SGPT serum glutamic pyruvate transaminase - LDH lactic dehydrogenase - CPK creatinine phosphokinase - MUG 4-methyl-umbelliferyl-alphad-glucoside     

Myopathy and neurogenic muscular atrophy in unexpected cardiopulmonary arrest

Background: Neuromuscular disorders can be the cause of sudden death of infants because of their weakness and gastroesophageal reflux (GER). Methods: Muscle biopsy and genetic studies were performed by usual method. Results: In this report four cases of infants with neuromuscular disorders (two cases of congenital myopathy and two cases of spinal muscular atrophy) who had unexpected cardiopulmonary arrest on arrival (CPAOA) are presented. Two of the cases did not show any symptoms, such as muscle weakness prior to CPAOA. The diagnosis was based on the results of the muscle biopsy and genetic examination. Conclusion: These results suggest that sudden infant death caused by neuromuscular disorders should be considered.     

Recent advances in diagnosis of the childhood muscular dystrophies

Abstract: Recent advances in molecular genetics research have revolutionised our understanding of the childhood muscular dystrophies. The first breakthrough came in 1987 with the identification of the gene for dystrophin, the protein that is abnormal in X-linked Duchenne muscular dystrophy. Dystrophin is bound to a complex of proteins in the muscle membrane, and primary abnormalities of these protein have now been identified as the cause of some autosomally inherited forms of muscular dystrophy. A group of transmembrane proteins known as α- (adhalin) β-, γ- and δ-sarcoglycan are deficient in autosomal recessive limb-girdle muscular dystrophy, and the extracellular matrix protein merosin (α2-laminin), is deficient in a subset of patients with congenital muscular dystrophy. Identification of primary deficiencies in these 'dystrophin associated proteins' will result in improved diagnostic accuracy, more accurate genetic counselling and, in some cases, the availability of prenatal diagnosis.     

Muscular form of glycogenosis type II (Pompe's disease).

An 11-year-old boy who was previously thought to have progressive muscular dystrophy was studied clinically, biochemically, and histologically. He was seen initially with an amyotonic syndrome with no clinical evidence of heart disease. Light and histochemical examination showed vacuolar degeneration and abnormal accumulation of glycogen in the muscular fibers. Electron microscopy showed aggregates of glycogen granules surrounded by a well-defined membrane, as in previously reported cases of type II glycogenosis. Enzymatic study disclosed that acid alpha-glucosidase was deficient in muscle, liver, and heart tissue, although neutral alpha-glucosidase was present within normal ranges. Measurement of acid and neutral alpha-glucosidase activity in muscle from the patient and his sisters and in urine from them and their parents indicated that his sisters are heterozygotes and his parents probably are heterozygotes. The disease was transmitted as an autosomal-recessive trait.     

Merosin-deficient congenital muscular dystrophy and cortical dysplasia.

Congenital muscular dystrophy (CMD) encompasses a heterogenous group of muscle disorders with autosomal recessive inheritance, characterized by muscular weakness and hypotonia at birth or within the first few months of life and developmental delay. Merosin-deficient CMD is a clinically distinct form which may be associated with significant abnormalities of the brain detectable by neuroimaging. We report two siblings of consanguineous parents with merosin-deficient CMD in an Irish family who in addition to the characteristic white matter abnormalities on neuroimaging, had occipital dysplasia. Clinical, electrophysiological muscle biopsy findings and neuroimaging were very similar in both cases. Although merosin-deficient CMD with white matter abnormalities on neuroimaging is well documented in the literature, the association with occipital dysplasia has only rarely been reported. The appearance of an identical cortical defect in these siblings suggests an underlying genetic mechanism.     

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。     

Acute post-streptococcal polymyalgia: Two new cases with a review of the literature

Two patients with acute post-streptococcal polymyalgia are described with a review of the seven cases previously reported cases. The common features are sudden onset of muscular pain with fever usually after an acute upper respiratory tract infection. Antistreptolysin O titre and inflammatory indexes are increased and muscle enzymes are normalConclusion Acute post-streptococcal polymyalgia should be considered as a possible diagnosis in every child complaining acute polymyalgia.     

Vimentin/desmin Immunoreactivity of Myofibres in Developmental Myopathies

Immunoreactivity for the intermediate filament proteins vimentin and desmin was studied in muscle biopsies of 33 children with neuromuscular diseases and in postmortem muscle of 15 fetuses and neonates at 8–42 weeks gestation. Fetal myotubes exhibited strong reactions for vimentin and desmin; reactivity was still present, though weaker, by 31 weeks and was no longer demonstrable at term. In X-linked myotubular myopathy (5 cases) myofibres showed strong reactivity for both vimentin and desmin; in myotonic dystrophy desmin but not vimentin had strong reactivity in myofibres of neonates and children. A similar but much weaker pattern of desmin reactivity was seen in nemaline rod disease and in congenital muscle fibre-type disproportion. The small myofibres in spinal muscular atrophy were reactive for both vimentin and desmin, as were regenerating myofibres in Duchenne muscular dystrophy and dermatomyositis. Acridine orange fluorochrome distinguished vimentin/desmin-reactive myofibres that were regenerating from those of developmental myopathies because the RNA fluorescence was strong in regenerating myofibres and in fetal myotubes, but was absent from myofibres in developmental disorders of muscle. A failure to regress of fetal cytoskeletal proteins may contribute to the apparent arrest in morphogenesis of myofibres. These stains are useful in studying the muscle biopsies of children with developmental myopathies because they demonstrate an aspect of muscle maturation not detected by standard histochemical methods.