Multicore myopathy associated with multiple pterygium syndrome and hypertrophic cardiomyopathy

A boy with multicore myopathy associated with multiple pterygium syndrome and hypertrophic cardiomyopathy is described. Light microscopy of biopsy samples from the skeletal muscle and myocardium revealed multiple cores in the muscle fibers in the former but their absence in the latter. These results suggest that the pathogenesis of the histologic changes might differ between skeletal muscle and myocardium, and that further electron microscopic examination be done on both types of specimen. The prognosis of multicore myopathy is not usually good when cardiac involvement is present.     

M-mode echocardiographic findings in children with idiopathic restrictive cardiomyopathy

Summary The M-mode echocardiographic findings in five pediatric patients, ages 4–15 years, with primary idiopathic restrictive cardiomyopathy, diagnosed by cardiac catheterization, and of 12 normal children (control group) are presented. The M-mode echocardiographic findings in patients with restrictive cardiomyopathy were (1) normal left and right ventricular end-diastolic dimension, (2) normal left ventricular posterior wall and interventricular septal thickness (three patients) or mild concentric hypertrophy (two patients), (3) normal opening and closing velocity of the mitral valve, (4) consistently enlarged left atrium (more than 40 mm) in all, and (5) right ventricular systolic time intervals compatible with pulmonary artery hypertension. The left ventricular ejection phase parameters (systolic time intervals, shortening fraction, and mean velocity of circumferential fiber shortening) were normal. Left ventricular relaxation phase parameters (diastolic function) were abnormal. The isovolumic relaxation time index was prolonged, 68±40 ms (±SD), in the study group as compared with 11±6 ms (±SD) in the control group (P<0.001). Percent relaxation of left ventricular posterior wall endocardium at 50% of diastole was decreased, 58±4% (±SD), in the study group as compared with 85±6% (±SD) in the control group (P<0.005). We conclude that M-mode echocardiography provides arelatively useful and specific noninvasive method for the diagnosis of primary restrictive cardiomyopathy in pediatric patients. This work was supported in part by NHLBI grant HL07436.     

Mitochondrial myopathy presenting as ataxia with dilated cardiomyopathy

Mitochondrial disorders are multisystem diseases with very heterogeneous clinical manifestations. Common cardiac features include cardiomyopathy and conduction defects. We report a fiveyear-old boy who presented with signs of congestive cardiac failure and was diagnosed to have dilated cardiomyopathy. Six months later, he developed progressively worsening ataxia, hypotonia, other cerebellar signs, hearing loss, severe sensory peripheral neuropathy and lactic acidosis. Electronmicroscopy of skeletal muscle biopsy was consistent with mitochondrial myopathy     

Outcomes of Berlin Heart EXCOR® pediatric ventricular assist device support in patients with restrictive and hypertrophic cardiomyopathy

The outcomes of pediatric ventricular assist device support in patients with diastolic heart failure have not been well described. This study reviews the North American experience with Berlin Heart EXCOR^® ventricular assist device implants in children with such physiology. The Berlin Heart clinical database was reviewed. Patients with primary diastolic dysfunction are included in this study. Twenty pediatric patients with restrictive cardiomyopathy (n = 13), hypertrophic cardiomyopathy (n = 3), or congenital heart disease with restrictive physiology (n = 4) who were supported with EXCOR^® were identified. Of these, nine (45%) were successfully bridged to transplant, one (5%) weaned from support, and 10 (50%) died after support was withdrawn. Of patients under age 3 years (n = 13), 38.5% survived, whereas those aged 3 or older (n = 7) had 71.4% survival (P = .35). Biventricular assist device (BiVAD) patients experienced a 27.3% survival, vs 77.8% for patients with left ventricular assist device only (P = .07). Primary causes of death included stroke, infection, acidosis, multisystem organ failure, and bleeding. Pediatric patients with diastolic heart failure comprise a high‐risk population for mechanical circulatory support. However, half of patients with this physiology have been successfully supported to explant with EXCOR^®. The trends toward higher mortality for younger patients and those receiving BiVAD support warrant consideration.     

Cardiomyopathy and multicore myopathy with accumulation of intermediate filaments

A girl affected by a restrictive cardiomyopathy with neuromuscular involvement is described. Morphological examination showed a pattern of multicore myopathy and with electron microscopy a sarcoplasmic accumulation of electron dense granular and filamentous material was demonstrated both in skeletal muscle and heart. This peculiar electron dense material corresponded to increased desmin in muscle and cardiac fibres and was demonstrated immunohistochemically.     

Fatal neonatal cardiomyopathy associated with cataract and mitochondrial myopathy

Three patients suffering from the neonatal form of a syndrome characterized by congenital cataract, hypertrophic cardiomyopathy, and mitochondrial myopathy are described. The patients died at 7, 10 and 18 days, respectively from cardiorespiratory failure. Mitochondrial abnormalities were observed in the heart and skeletal muscle. Despite the presence of a severe lactic acidaemia pointing to a disturbed pyruvate oxidation rate in vivo, a normal pyruvate oxidation rate was demonstrated in skeletal muscle homogenates. The activities of several enzymes of the mitochondrial respiratory chain appeared to be normal, indicating an intact respiratory chain. A myoglobinopenia could be excluded. The activities of some mitochondrial enzymes and the concentration of myoglobin increase with age.Abbreviations ATP adenosine triphosphate - CrP creatine phosphate     

Unclassified familial cardiomyopathy with ventricular dysrhythmia

Summary The case is described of a boy with some right ventricular dysplasia and episodes of ventricular tachycardia of left bundle branch block pattern who had symptoms from the age of 1 month. Angiography and cardiac biopsy demonstrated major involvement of the left ventricular myocardium. A sister of the patient presented at the age of 2 months with predominantly left ventricular cardiomyopathy; clinical signs and angiography suggested the presence of right ventricular dysplasia as well. She died suddenly at the age of 9 years. Her brother, now aged 14 years, is being treated with antiarrhythmic drugs. The hypothesis of this cardiomyopathy being a variant of arrhythmogenic right ventricular dysplasia syndrome is discussed.     

Primary restrictive cardiomyopathy in childhood

Restrictive cardiomyopathy is one of the rarest forms of cardiomyopathy in childhood and is associated with very poor prognosis (median transplant-free survival approximately 2 years). Little progress has been made in our understanding of the etiology of this condition, and most cases are considered ‘idiopathic’ in nature. No strong predictors of outcome have been identified and sudden death is common, even among those with few symptoms. Disappointingly, no effective therapies have emerged other than heart transplantation. Studies of familial cases suggest genetic and phenotypic overlap with other forms of cardiomyopathy, especially hypertrophic cardiomyopathy. Future research priorities include more careful delineation of phenotype(s), search for genetic etiologies and molecular mechanisms of disease, and studies to identify prognostic factors. Given the rarity of this condition, future studies will require collaboration among large numbers of centers following the models developed by the US Pediatric Cardiomyopathy Registry and the National Australian Childhood Cardiomyopathy Study.     

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。     

A new congenital myopathy in a Norwegian family

A 6-y-old boy presented with a mild, and apparently non-progressive, congenital myopathy, primarily affecting explosive movements such as running and jumping. Five other cases, spanning four generations, were identified in his family. A dominant inheritance pattern was suggested. Quadriceps muscle histology showed a selective type II fibre atrophy, which is otherwise considered a non-specific change associated with a number of conditions. Conclusion: A Norwegian boy with an inherited muscle weakness is presented. Based on clinical and laboratory investigations, and in light of the inheritance pattern, a previously undescribed congenital myopathy is suggested.     

限制型心肌病患儿致病基因检测1例报告

目的分析TNNI3基因变异致可疑限制型心肌病的临床表型及基因型。方法回顾分析1例可疑限制型心肌病患儿的临床资料。结果患儿为4岁8月龄女孩,因咳嗽、发热,心电图异常入院。患儿心电图示双心房负荷重,左心室高电压;超声心动图示全心扩大,室壁运动减弱;心功能不全;少量心包积液;二尖瓣关闭不全(中量反流);肺动脉高压。患儿于入院2个月前曾有上楼时口唇发绀史。基因检测提示患儿存在TNNI 3基因c.575G>A杂合变异,其父母未携带该变异,属于新发变异。该变异使TNNI 3基因192位的精氨酸被组氨酸取代。多物种对比发现该位点具有高度保守性。各种预测软件提示该变异为有害变异。结论TNNI3基因c.575G>A(p.Arg192His)杂合变异很可能是本例患儿的致病变异。     

Danon disease with typical early-onset cardiomyopathy in a male: focus on a novel LAMP-2 mutation

Abstract:  We report a case of a 16-yr-old male with Danon disease caused by a novel mutation in the LAMP-2 gene. Mutations in the LAMP-2 gene result in the absence of LAMP-2 on immunohistochemical staining of muscle tissue, thus defining Danon disease, a rare X-linked myopathy. It is characterized clinically by HCM or left ventricular hypertrophy, a WPW pattern on ECG, variable degrees of muscular weakness (skeletal myopathy), mental retardation, and retinal changes. The patient presented with severe skeletal muscular weakness and respiratory failure. He also had a history of two OHTs, the first one for severe HCM and the second for allograft rejection. The patient's myopathy was initially presumed to be exclusively related to steroid-induced "critical care myopathy." However, further evaluation with a thigh muscle biopsy revealed autophagic vacuoles with sarcolemnal features suggestive of a lysosomal storage disorder. DNA analysis ultimately identified a previously unreported hemizygous IVS6+3_+6delGAGT splice site deletion mutation in the LAMP-2 gene located within the 5' splice site of intron 6, consistent with Danon disease.     

Congenital hypertrophic cardiomyopathy,cataract, mitochondrial myopathy and defective oxidative phosphorylation in two siblings with Sengers-like syndrome

We describe two siblings with a Sengers-like syndrome, who presented with congenital hypertrophic cardiomyopathy, infantile cataract, mitochondrial myopathy, lactic acidosis and normal mental development. A mitochondrial adenine nucleotide translocator 1 (ANT1) defect was detected since the ANT1 protein was not detectable by immmunoblotting in muscle samples of the patients. Additionally to these features of classical Sengers syndrome (OMIM 212350), we found that the mitochondrial oxidative phosphorylation, measured by biochemical analysis, was severely compromised in skeletal muscle in both children. Biochemical and morphological analysis of the fibroblasts revealed normal results. The association of significantly decreased pyruvate oxidation rates, deficient energy production and decreased multiple mitochondrial enzyme-complex activities in the muscle samples of our patients is a new finding which differs from previous results in patients with Sengers syndrome. Conclusion:we recommend a muscle biopsy and the biochemical analysis of the oxidative phosphorylation system in patients with muscle hypotonia, cardiomyopathy and congenital or infantile cataract.Abbreviations ANT1 adenine nucleotide translocator 1 - COX cytochrome c oxidase - SDH succinate dehydrogenase     

儿童心动过速性心肌病临床特点及与扩张型心肌病对照分析

目的探讨儿童心动过速性心肌病(TIC)的临床特点,治疗及预后。方法回顾分析2013年1月至2020年9月住院治疗的18例TIC患儿的临床资料,并进行随访。选取同时期住院扩张型心肌病(DCM)患儿40例,比较TIC组和DCM组临床特点、治疗情况及预后。结果TIC组18例患儿中,心律失常类型以房性心动过速(简称房速)为主(15例,83.3%)。15例房速中,8例为持续无休止性房速。中重度左心收缩功能下降者(n=7)心律失常占总心率百分比为100%(91.9%~100%),轻度下降者(n=7)为38.7%(32.9%~99.8%),差异有统计学意义(P<0.05)。18例患儿均首先予以药物治疗,6例药物复律后维持窦性心律,12例药物转复后不能维持窦性心律者中7例行射频消融术,均成功复律,其余5例予药物控制心律及心室率,心室率明显下降,心律失常发作频率及负荷明显降低。与DCM组相比,TIC患儿诊断年龄较小,急性期心率较快,急性期HR指数较大、心功能Ⅲ~Ⅳ级发生比例较低,首次就诊时经体表面积标准化后的左心室舒张末期内径Z值(LVEDD-Z)较小,左心室射血分数(LVEF)、左室短轴缩短率(LVFS)较高,房速比例较高,室速比例较低,24小时动态心电图总心率较高,心律失常占总心率百分比较高,治疗2周内血B型利钠肽(BNP)水平升高的比例较低,治疗前BNP与治疗后2周内BNP的比值(BNP-R)较大,差异均有统计学意义(P<0.05)。结论心动过速显著,异位节律心动过速负荷高,同时合并左心收缩功能受损及心脏扩大,复律或控制心室率后受损左心收缩功能恢复快且完全,心脏扩大恢复明显需多考虑TIC诊断。TIC患儿总体预后较好。     

Neuroblastoma presenting with dilated cardiomyopathy

We report an infant with neuroblastoma who presented with dilated cardiomyopathy. A 3-month-old girl presented with dilated cardiomyopathy diagnosed as stage III neuroblastoma. Since total resection was impossible, chemotherapy was started. Cardiomyopathy was normalized by improvement of neuroblastoma. The prompt improvement of cardiac function following treatment of neuroblastoma suggested that cardiomyopathy in this patient was caused by the increase in catecholamines secreted by neuroblastoma and that reduction in catecholamines by treatment of neuroblastoma led to improvement in the cardiomyopathy.     

Hypertrophic cardiomyopathy and transposition of great arteries associated with maternal diabetes and presumed gestational diabetes

Maternal diabetes mellitus affects the foetal heart both structurally and functionally. In early gestation, it has a teratogenic effect causing defects of primary cardiogenesis. In late gestation, it causes a unique form of hypertrophic cardiomyopathy. We report an infant of a diabetic mother and an infant where there was presumed gestational diabetes during the pregnancy who presented with combined severe hypertrophic cardiomyopathy and complex transposition of the great arteries. This rare combination of structural and functional cardiac abnormalities reflects the different mechanisms and timings of injury that may occur to the foetal heart in association with maternal diabetes and has not been previously reported. The combination has significant implications regarding medical and surgical management, and necessitates prolonged supportive therapy whilst awaiting regression of the hypertrophic cardiomyopathy followed by delayed arterial switch operation. CONCLUSION: We describe two infants with the unusual combination of both hypertrophic cardiomyopathy and transposition of the great arteries. One was an infant of a diabetic mother, and the second was associated with presumed gestational diabetes.     

Neonatal nemaline myopathy presenting with multiple joint contractures

A sporadic case of the rare and most severe neonatal form of nemaline myopathy is reported. Intrauterine manifestation included reduced fetal movements and breech position with a normal amount of amniotic fluid. After delivery by Caesarian section at 34 weeks of gestation the infant boy, who was not asphyctic, failed to establish spontaneous breathing and required immediate intubation and ventilation. Marked muscular hypotonia and weakness persisted and reflexes remained absent. Hip dislocation, joint contractures, absent palmar creases, prominent lateral palatal ridges and cryptorchidism were interpreted as consequent to prenatal paralysis. The boy died after 5 h due to hyaline membrane disease and meconium aspiration. At autopsy the skeletal muscles were found to be hypoplastic. The muscle fibres contained numerous rods, a typical finding of nemaline myopathy.Nemaline myopathy should be considered in fetuses and newborns with multiple joint contractures, severe muscular weakness and respiratoy insufficiency.     

Cytochrome c oxidase deficiency in a child with isolated myopathy

Cytochrome c oxidase (COX) deficiency is the most commonly recognized respiratory chain defect in childhood. The disease is clinically heterogeneous with phenotypes including Leigh syndrome, hepatic failure and myopathies. COX deficiency has been associated with mitochondrial DNA mutations in COX I, II, and III with large-scale deletions of the mitochondrial genome and with point mutations in mitochondrial tRNA genes. Here we report on a 3.5-year-old girl with a rare type of isolated myopathy due to COX deficiency.