1/9. Cardiac manifestations of congenital fiber-type disproportion myopathy.Cardiac involvement has not been a reported feature of congenital fiber-type disproportion myopathy. We describe two children, aged 13 years and 1 year, respectively, who presented with serious cardiac symptomatology in conjunction with congenital fiber-type disproportion. One child developed dilated cardiomyopathy and medically intractable congestive heart failure necessitating cardiac transplantation at the age of 13 years. The second (unrelated) child developed atrial fibrillation with rapid atrioventricular conduction requiring treatment with digoxin. Skeletal muscle biopsy findings in both children showed congenital fiber-type disproportion with no evidence of a structural, dystrophic, or metabolic myopathy. adenosine triphosphatase (ATPase) reacted sections showed type I hypotrophy with a predominance of type I fibers, confirmed by histogram analysis. Examination of the heart from patient 1 at the time of transplantation confirmed dilated cardiomyopathy with hypertrophic myocardiocytes. Although cardiomyopathy is commonly associated with other childhood myopathies, to our knowledge it has not been a feature in reported cases of congenital fiber-type disproportion. We recommend close cardiac assessment, with annual electrocardiograms, of children with congenital fiber-type disproportion.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
2/9. Homozygosity for a nonsense mutation in the alpha-tropomyosin slow gene TPM3 in a patient with severe infantile nemaline myopathy.The nemaline myopathies are muscle disorders of variable severity and age of onset, with characteristic nemaline bodies in the sarcoplasm. genes for dominant (NEM1) and recessive (NEM2A) nemaline myopathy have been localised to chromosomes one and two, respectively. A missense mutation in the alpha-tropomyosin gene (TPM3) has been associated with NEM1 in one family. Probands from 76 other nemaline myopathy families have now been screened for TPM3 mutations. One proband, who was not noted to have any weakness neonatally, but who died at 21 months of age, was shown to be homozygous for a single strand conformation polymorphism (SSCP) in skeletal-muscle-specific exon 1 of TPM3. Sequencing revealed homozygosity for a nonsense mutation at codon 31 (CAG to TAG). The patient should have no functioning alpha-tropomyosin slow protein. The nemaline bodies in this patient were exclusively in type one fibres, consistent with the expression of TPM3 only in type one fibres.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
3/9. Mild phenotype of nemaline myopathy with sleep hypoventilation due to a mutation in the skeletal muscle alpha-actin (ACTA1) gene.Nemaline myopathy is a clinically and genetically heterogeneous condition. The clinical spectrum ranges from severe cases with antenatal or neonatal onset and early death to late onset cases with only slow progression. Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42. We present a 39-year-old lady with a mild form of nemaline myopathy, whom we have followed over a period of 25 years. She presented at the age of 7 years with symptoms of mild axial and proximal muscle weakness. The overall course was essentially static, but at 36 years, she went into life-threatening respiratory failure, for which she is currently treated with night-time ventilation. Muscle biopsies at 12, 17 and 39 years of age showed typical nemaline rods, particularly in type 1 fibres. Areas with unevenness of oxidative stain were present in the second and third biopsies. The presence of rods and core-like areas was confirmed on electron microscopy. There was no detectable alteration in actin expression immunocytochemically. A dominant missense mutation in the skeletal muscle alpha-actin gene (ACTA1) was found. This case illustrates the clinical and genetic heterogeneity of nemaline myopathy, and one phenotype of the wide spectrum of severity caused by mutations in the skeletal muscle alpha-actin (ACTA1) gene. In addition, it shows the diversity of pathological features that can occur in congenital myopathies due to mutations in the same gene.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
4/9. Nemaline myopathy: description of an adult onset case.Nemaline myopathy is a rare congenital muscle disease, with neonatal or adult onset. We report clinical and ultrastructural study of a 73-year-old woman whose symptoms manifested at age 40 years with proximal muscle weakness, nocturnal cramps, muscle pain and walking impairment. Muscle biopsy showed rods and other typical findings suggesting nemaline myopathy. This myopathy should be taken into account in the differential diagnosis of adult onset myopathies. Only ultrastructural examination allows an exact diagnosis.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
5/9. Intranuclear rod myopathy, a rare and morphologically striking variant of nemaline rod myopathy.A 4-year-old boy with muscle weakness underwent skeletal muscle biopsies. light microscopy showed distinct eosinophilic inclusions within the majority of muscle cell nuclei, but none in the cytoplasm. Electron microscopy revealed crystalline, round to rod-shaped inclusions in the muscle cell nuclei. The inclusions stained positively for alpha-actinin. Intranuclear inclusions identical to those seen here have been described in rare cases of nemaline rod myopathy, though almost always together with classic intracytoplasmic rods. This case illustrates the importance of electron microscopy in the diagnosis of rare myopathies and in the characterization of cellular inclusions of unknown origin.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
6/9. scoliosis associated with central core disease.A 12-year-old Japanese girl who had progressive severe scoliosis but with minimal muscle weakness in the extremities was found to have central core disease. In her muscle biopsies obtained from the biceps brachii and paraspinous muscles, there was type 1 fiber atrophy and predominance, as is commonly seen in congenital myopathies, but the core structure was identified only in the former. To determine whether scoliosis is a prominent feature of this disease, we reviewed 10 patients with central core disease in our laboratory and found 6 ambulant patients who had mild-to-moderate scoliosis. Since kyphoscoliosis becomes prominent as muscle weakness progresses to loss of ambulation in most muscle diseases, this disproportionate spinal involvement in central core disease appears to be a striking feature. All patients with 'idiopathic' scoliosis deserve a careful neurological evaluation, even if they have minimal muscle symptoms in the extremities.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
7/9. Nemaline myopathy: two autopsy reports.Nemaline myopathy belongs to the group of congenital non-progressive myopathies; however, in rare cases death occurs in early infancy. We report two cases of rapidly fatal nemaline myopathy. The first patient, who died at the age of 26 months, showed atrophy of type 1 fibers containing numerous rods in biopsy sections. biopsy of the second patient, who had died at the age of 5 months, revealed severe maturational arrest and myopathy, but rods were so rare that diagnosis could only be made at the ultrastructural level. autopsy of both patients showed that atrophy of type 1 fibers and maturational arrest had disappeared in the very same muscles; rods had moved to a central position in the first and significantly increased in number in the second case. Diaphragma muscles contained abundant amounts of rods in both cases. The cardiac musculature showed a few rods only in the first patient, who had developed heart insufficiency 11 months prior to death. Immunohistochemical analysis showed that rods did not contain desmin or ubiquitin.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
8/9. Nemaline myopathy in the neonate: two case reports.Nemaline myopathy, one of the most benign myopathies in older children and adults, may be rarely associated with early death in the neonate. The authors report two cases, describing the ante- and postnatal clinical courses. family history may help in establishing the diagnosis, but this was not the case in the two infants described. Above all, the diagnosis is based on the results of muscle biopsy. CONCLUSION: Nemaline myopathy may lead to early death in the neonate.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
9/9. Central core disease associated with scoliosis: report of one case.A 13 year-old girl with scoliosis and central core disease is reported. She was noted to have mild psychomotor developmental delay since early infancy. scoliosis with minimal muscle weakness was noted at about five years old. The neurological examination disclosed absent knee jerk. The spine MRI showed no significant finding. The serum CK revealed 518 U/L. The muscle biopsy obtained from the quadriceps femoris muscle showed Type 1 fiber atrophy and predominance, as is commonly seen in congenital myopathies. Under nicotinamide adenine dinucleotide dehydrogenase (NADH) and succinate dehydrogenase (SDH) stains, core structures were identified and the diagnosis of central core disease (CCD) was made. Since kyphoscoliosis usually becomes prominent as muscle weakness progresses to loss of ambulation in other myopathies, the disproportionate spinal involvement in central core disease appears to be a striking feature. We suggest that all patients with idiopathic scoliosis deserve a thorough neurological evaluation if congenital myopathies are suspected. Muscle biopsy should also be recommended for a confirmatory diagnosis even if only minimal muscle weakness present. Besides, early detection of CCD helps us to identify the population who are at a higher risk for malignant hyperthermia.- - - - - - - - - - ranking = 3keywords = myopathies (Clic here for more details about this article) |