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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A subset of patients with congenital muscular dystrophy (CMD) are deficient for the extracellular matrix protein, merosin. Although the aetiology of merosin-positive CMD is as yet unknown, abnormalities of other structural muscle-specific proteins are likely to be involved. The alpha-actinins are actin-binding proteins related to dystrophin. We studied expression of the skeletal muscle isoforms of alpha-actinin (alpha-actinin-2 and alpha-actinin-3) in muscle biopsies from 12 patients with pure CMD (including one with a merosin abnormality), two with unclassified CMD and central nervous system (CNS) involvement, and three with other neuromuscular disorders. Four specimens exhibited deficient alpha-actinin-3 staining by immunofluorescence and/or Western blot analysis. In one, this pattern may be a secondary consequence of marked type 1 fibre predominance, but the other three biopsies contained abundant type 2 fibres where alpha-actinin-3 is normally expressed. Three alpha-actinin-3-deficient patients had pure CMD and presented in the newborn period with muscle weakness, hypotonia and arthrogryposis. The fourth had a dystrophic muscle biopsy and CNS involvement. These results suggest that deficiency of alpha-actinin-3 may be a marker for a subset of patients with CMD. It remains to be determined whether the deficiency of alpha-actinin-3 reflects ACTN3 gene mutations or is a secondary phenomenon.
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PMID:Deficiency of a skeletal muscle isoform of alpha-actinin (alpha-actinin-3) in merosin-positive congenital muscular dystrophy. 888 51

We report clinical and pathological findings in 9 children affected by congenital muscular dystrophy with normal or borderline intelligence and hypodensity of cerebral white matter (CMD-HWM), also frequently called 'occidental or western form of cerebro-muscular dystrophy' (OCMD). Our patients have uniform, distinct, clinical presentation that includes: normal or subnormal intelligence, severe, slowly progressive motor disability, high rate of facial involvement and dysmorphic aspect, increased creatine kinase levels and variable degrees of abnormal, radiographic, cerebral white matter pattern. By comparing our cases with previous reports we suggest that this subtype of CMD is not uncommon in Brazil and it is represented by a particularly severe and homogeneous clinical picture with important motor disability. The immunohistochemical staining for merosin, performed on the muscle biopsy of 6 among 9 patients, showed that all are merosin negative.
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PMID:Congenital muscular dystrophy with cerebral white matter hypodensity. Correlation of clinical features and merosin deficiency. 890 44

In muscle biopsy specimens from three patients with merosin-negative congenital muscular dystrophy (CMD), there was marked variation in fiber size with evidence of necrotic and regenerating processes and with marked interstitial fibrosis. No muscle fibers or intramuscular nerves stained with merosin antibody. On electron microscopy, the basement membrane of all the muscle fibers was very poorly discernible and there were occasional disruptions, while the basement membrane of the Schwann cells was well preserved. On the other hand, the sarcolemmal basement membrane in merosin-positive CMD was well preserved even in patient with severe interstitial fibrosis. It remains to be determined how the defective basement membrane in merosin-negative CMD induces defective sarcolemma and eventual fiber necrosis.
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PMID:Basement membrane abnormality in merosin-negative congenital muscular dystrophy. 892 8

A particular form of congenital muscular dystrophy with merosin deficiency has recently been described. Magnetic resonance imaging has shown that affected children show brain abnormalities. We investigate the localization of merosin in the normal human brain by immunohistochemistry. Other organs, such as the kidney, lung and liver, were also included in this study. We show that in the normal central nervous system merosin is localized in the basement membrane of blood vessels. No expression of merosin was found at the level of the liver and lungs, whereas the glomerular mesangial matrix of the kidney was intensely positive. These results suggest that merosin deficiency in the basement membrane of blood vessels in the central nervous system could play an important role in the physiopathology of brain abnormalities found in children affected by the congenital muscular dystrophy associated with merosin deficiency. Furthermore, the potential absence of merosin in the glomerular mesangial matrix of the kidney suggests a multi-system involvement.
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PMID:Localization of merosin in the normal human brain: implications for congenital muscular dystrophy with merosin deficiency. 892 21

In the classical form of congenital muscular dystrophy (CMD), subclinical brain involvement is frequent. In order to establish the natural evolution of CNS alterations in this type of CMD, the cerebral functions of 12 cases were examined longitudinally for a mean period of 8 years. There were 7 boys and 5 girls, with a mean age of 5 years at first evaluation and 13 at the last one. Merosin expression in muscle fiber basement membrane, evaluated in 10 of them, was normal in 6 and deficient in 4. CNS conditions were followed up by repeated neuropsychiatric examinations, intelligence tests, EEG and brain CT scan and/or MRI. Eight of the 12 patients (including the 4 with merosin-deficiency) had normal intelligence, while 4 had mild to moderate mental retardation: in all the intellectual ability was unchanged during the follow-up study. CT scan detected minor brain alterations in 9 patients: 6 of these, the 4 with merosin deficiency and 2 others in whom merosin was not evaluated, presented leukoencephalopathy: on neuroimaging reappraisal it was unchanged in 3, improved in 2 and worse in 1 (a merosin-deficient case). Cerebellar alterations or mild ventricular dilatation were detected in 8 cases, including 3 merosin-non-deficient ones: these abnormalities were unchanged at the last study by CT and MRI, as were the normal neuroimaging findings observed in 3 other cases. Overall, during our study the brain alterations found in classical CMD showed a stationary or an improving course; progressive worsening was observed only in 1 of 4 merosin-deficient cases with leukoencephalopathy.
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PMID:Brain alterations in the classical form of congenital muscular dystrophy. Clinical and neuroimaging follow-up of 12 cases and correlation with the expression of merosin in muscle. 893 20

We found partial merosin deficiency in a boy presenting at 12 yr with marked limb weakness and a waddling gait. Magnetic resonance imaging (MRI) showed the characteristic white matter abnormalities of merosin-negative congenital muscular dystrophy. There were also peripheral demyelinating polyneuropathy and evoked potential abnormalities. Unlike classic merosin-negative congenital muscular dystrophy, however, our patient was less hypotonic and weak and was able to achieve independent walking. Both by immunohistochemistry and Western blot merosin was shown to be moderately reduced. By immunostaining the alpha 1 laminin chain was overexpressed and beta 1 laminin chain was reduced. A spectrum of clinical phenotypes is likely to become evident in merosin-deficient patients in relation to the discovery of a range of molecular defects in, and variable expression of, this protein.
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PMID:Mild clinical phenotype in a 12-year-old boy with partial merosin deficiency and central and peripheral nervous system abnormalities. 893 2

Ten laminin alpha2-deficient patients were identified by both immunofluorescence and immunoblotting (30% of congenital muscular dystrophy patients tested). Three of the laminin alpha2-deficient patients were carrying a diagnosis of infantile polymyositis prior to immunostaining studies. The clinical features in the 10 merosin-deficient patients were homogeneous, with severe floppiness at birth, delay in achievement of motor milestones, and magnetic resonance imaging findings of white matter changes with normal intelligence. The 10-kb laminin alpha2-coding sequence was screened for causative mutations by reverse transcriptase-polymerase chain reaction/single-stranded conformational polymorphism analysis in muscle biopsy specimens from 5 patients, followed by automatic sequencing of aberrant conformers. Clear loss-of-function deletion mutations were identified in both alleles of 1 patient. Muscle histopathology in this patient showed a striking inflammatory infiltrate of T cells and B cells. Reexamination of biopsy specimens from other laminin alpha2-deficient patients showed minor signs of inflammation in each. Based on these findings and the histological and clinical picture suggesting failure of muscle regeneration, a pathogenesis model for this major subset of congenital muscular dystrophy is proposed. Our data show that muscle histopathology showing a neonatal inflammatory process should be considered consistent with congenital muscular dystrophy.
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PMID:Congenital muscular dystrophy with primary laminin alpha2 (merosin) deficiency presenting as inflammatory myopathy. 895 20

Of the various muscular dystrophies, the dystrophinopathies are the most common, accounting for the majority of male muscle disease patients and for about 10% of female patients referred for the evaluation of muscular dystrophy or persistent high serum creatine kinase values (hyperCKemia). The approach to diagnosis and family genetic counseling for the dystrophinopathies is now well established, and implementation of carrier detection and prenatal diagnosis has dramatically decreased the incidence of familial cases. With the decreasing observation of a positive family history in newly ascertained cases, molecular genetic and protein studies become imperative for accurate diagnosis. Genetic counseling in families of isolated cases can still be problematic. There is a wide range of opinions regarding the management of Duchenne muscular dystrophy, with surgical interventions (eg, tendon lengthenings and spinal fusion), steroid use, and extent of respiratory support actively debated. There has been progress in defining the underlying cause of disease for some patients of muscular dystrophy who have normal dystrophin findings. Nearly all patients with proximal, hyperCKemic muscular dystrophy who have normal dystrophin show no family history of the disorder, consistent with autosomal recessive disease. Approximately 5% of both boys and girls with childhood-onset dystrophy and normal dystrophin have been found to have mutations in one of the four sarcoglycan proteins identified to date. Also, approximately half of the patients with congenital muscular dystrophy show deficiency of a component of the muscular extracellular matrix. (merosin/laminin-alpha 2). In this review, we give a short primer on relevant muscle structure and function, followed by a series of case reports on patients referred for molecular testing that illustrate the diagnostic protocols, range of clinical presentations, and genetic counseling options in the work-up of proximal muscular dystrophy and hyperCKemia.
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PMID:HyperCKemic, proximal muscular dystrophies and the dystrophin membrane cytoskeleton, including dystrophinopathies, sarcoglycanopathies, and merosinopathies. 901 56

The laminins are a family of structural basement membrane components with major influences on cells. They are high molecular weight glycoproteins composed of three different but homologous chains, alpha, beta and gamma. At present 10 different chains have been identified. Each chain has a distinct structural organization of domains, some of which have been assigned biological activities, including self-assembly and interactions with other proteins. The particular importance of laminins for the formation and stability of cell adhesion complexes is highlighted in severe inherited diseases of muscle and skin. Merosin is the collective name for laminins that share a common subunit, the laminin alpha 2 chain. Merosin-deficient congenital muscular dystrophy (CMD) is caused by mutations in the laminin alpha 2 chain gene. The skin disease Herlitz junctional epidermolysis bullosa is caused by mutations in any of the laminin alpha 3, beta 3 or gamma 2 chain genes. The medical importance of laminins provides a further impetus to study the basic structure-function relationships in laminins in order to understand genotype-phenotype relationships and to design prenatal diagnostic tests and therapies aimed at compensating for specific defects.
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PMID:Merosin/laminin-2 and muscular dystrophy. 902 48

Diffuse white matter changes on brain imaging and peripheral neuropathy are associated features of merosin-deficient congenital muscular dystrophy (CMD). In this report we describe the early manifestation and evolution of brain changes, and the involvement of the peripheral nervous system in a female infant with merosin-deficient CMD diagnosed in the neonatal period who had sequential clinical, neurophysiological and magnetic resonance imaging (MRI) assessment. Both MRI and nerve conduction velocity in the first week of life failed to demonstrate any abnormality. By 6 months of age both nerve conduction and MRI were abnormal. White matter changes became more evident on a further scan at 1 yr of age and this pattern remained unchanged on the following scan performed at 17 months of age. Our findings suggest a failure in the physiological maturation process of myelination of both the central and peripheral nervous system.
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PMID:Sequential study of central and peripheral nervous system involvement in an infant with merosin-deficient congenital muscular dystrophy. 902 50


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