Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a rare case of an infant with congenital muscular dystrophy who presented at birth with marked generalized hypotonia and normal mental development. Creatinine phosphokinase (CPK) level was markedly raised; however no white matter abnormalities were detected by brain imaging techniques. Immunohistochemical staining for merosin (laminin alpha 2) was negative, thereby confirming merosin-deficient congenital muscular dystrophy.
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PMID:Merosin negative congenital muscular dystrophy: a short report. 1465 62

The congenital muscular dystrophies (CMD, MDC) represent a heterogeneous group of autosomal recessive disorders manifesting in infancy by muscle weakness and hypotonia. Approximately 40% of patients with CMD have a primary deficiency of the laminin alpha 3. chain of merosin (laminin-2) due to mutations in LAMA2 gene. Laminin-2 bound to alpha-dystroglycan forms a link between actin--associated cytoskeletal proteins and the components of extracellular matrix. Disruption of this axis is responsible for several forms of muscular dystrophy. A unique case of congenital muscular dystrophy simulating a juvenile polymyositis in a muscle biopsy is presented. A profound reduction of alpha-dystroglycan and less pronounced secondary deficiency of alpha 2-laminin were found. All known forms of CMD were excluded, and the disorder was diagnosed as so far undescribed form of CMD. The mutation in a gene encoding the protein, that seems to play a role in a glycosylation of alpha-dystroglycan, is presumed.
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PMID:[A unique case of congenital muscular dystrophy]. 1523 18

The congenital muscular dystrophies (CMD) are a heterogeneous group of autosomal recessive disorders, which present within the first 6 months of life with hypotonia, muscle weakness and contractures, associated with dystrophic changes on skeletal muscle biopsy. We have previously reported a large consanguineous family segregating merosin-positive congenital muscular dystrophy, in which involvement of known CMD loci was excluded. A genome-wide linkage search of the family conducted using microsatellite markers spaced at 10-Mb intervals failed to identify a disease locus. A second scan using a high-density SNP array, however, permitted a novel CMD locus on 4p16.3 to be identified (multipoint LOD score 3.4). Four additional consanguineous CMD families with a similar phenotype were evaluated for linkage to a 4.14-Mb interval on 4p16.3; however, none showed any evidence of linkage to the region. Our findings further illustrate the utility of highly informative SNP arrays compared with standard panels of microsatellite markers for the mapping of recessive disease loci.
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PMID:Localisation of merosin-positive congenital muscular dystrophy to chromosome 4p16.3. 1588 97

Congenital muscular dystrophy (CMD) composes a group of disorders characterized by hypotonia and muscular weakness noticed in the first year of life. The Ullrich's form is characterized by proximal joint contractures and distal hiperextensibility. About 40% of these patients present mutations in one of the genes that codify the sub-units of the collagen VI protein (COL6), producing total or partial deficiency of the protein expression. We analyzed, through immunohistochemistry, the expression of COL6 in muscle fragments of 50 patients with CMD; 20 of them presented merosin expression deficiency. We identified 4 cases with total COL6 deficiency (8% of the total), representing 13% of the cases with normal merosin expression. The histological findings of patients with deficiency of COL6 were indistinguishable from other forms of CMD, but milder than that abnormalities observed in merosin deficient patients. In three COL6 deficient patients were observed hypotonia and weakness in the neonatal period, delayed of motor milestones, muscular retractions of knees and elbows, distal joint hiperextensibility and congenital hip dislocation (two patients). One patient lost the ability to walk; and one died due to respiratory problems. The analysis of COL6 expression, as well as merosin expression, in the muscle tissue from CMD patients, can be important for identification and phenotypic characterization of different CMD subtypes.
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PMID:[Analysis of the expression of collagen VI in congenital muscular dystrophy]. 1605 8

The congenital muscular dystrophies (CMD) are clinically and genetically heterogeneous. The merosin (laminin alpha2 chain) deficient form (MDC1A), is characterized clinically by neonatal hypotonia, delayed motor milestones and associated contractures. It is caused by deficiency in the basal lamina of muscle fibers of the alpha2 chain of laminins 2 and 4 (LAMA2 gene at 6q22-23). Laminin alpha2 chain is also expressed in fetal trophoblast, which provides a suitable tissue for prenatal diagnosis in families where the index case has total deficiency of the protein. This article reports the collective experience of five centers over the past 10 years in 114 prenatal diagnostic studies using either protein analysis of the chorionic villus (CV) of the trophoblast plus DNA molecular studies with markers flanking the 6q22-23 region and intragenic polymorphisms (n=58), or using only DNA (n=44) or only protein (n=12) approaches. Of the 102 fetuses studied by molecular genetics, 27 (26%) were predicted to be affected while 75 (74%) were considered as unaffected, with 52 (51%) being heterozygous, thus conforming closely to an autosomal recessive inheritance. In 18 of the 27 affected fetuses, the trophoblast was studied by immunocytochemistry and there was a total or only traces deficiency of the protein in CV basement membrane in all. In 10 cases material from the presumably affected fetus was available for analysis after termination of the pregnancy and immunohistochemical study confirmed the diagnosis in all of them. Prenatal studies of 'at risk' pregnancies in the five centers produced neither false negative (merosin-deficiency in CVs in a normal fetus), nor false positive (normal merosin expression in CVs and affected child), indicating the reliability of the technique, when all the necessary controls are done. Our experience suggests that protein and DNA analysis can be used either independently or combined, according to the facilities of each center, to provide accurate prenatal diagnosis of the MDC1A, and have an essential role in genetic counseling.
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PMID:Prenatal diagnosis in laminin alpha2 chain (merosin)-deficient congenital muscular dystrophy: a collective experience of five international centers. 1608 89

Congenital muscular dystrophy (CMD) is a heterogeneous group of disorders characterized by early onset of hypotonia and weakness. Almost 50% of the cases are caused by primary deficiency of a protein named merosin (MD), and present a homogenous phenotype with a severe motor and respiratory involvement. Eleven children with clinical and histological diagnosis of CMD-MD, aged of 3 to 15 years, were studied using the manual muscle testing (Medical Research Council), goniometric analysis, motor ability and day life activities (Barthel index) scales, with the objective to characterize the main motor function limitations. The muscular groups most affected were cervical flexors, paravertebral and proximal portions of limbs. The muscular groups of upper limbs were as affected as the lower limbs, and the extensors were more affected than the flexors groups. All children had severe muscular retractions on the hip, knee and elbow. Other frequent deformities were scoliosis and equinus-varum feet. No children presented the motor ability to walk, stand up and crawl; and all of them were classified as dependents or semi-dependents in the day life activities scale. Our findings confirm the severe and diffuse involvement of skeletal muscle in CMD-MD patients, producing serious motor limitations and deformities.
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PMID:[Motor function evaluation in merosin-deficient congenital muscular dystrophy children]. 1610 Sep 78

Congenital muscular dystrophy (CMD) is a heterogeneous group of neuromuscular disorders characterized by muscle weakness and hypotonia at birth or within the first few months of life. It is inherited in an autosomal recessive pattern. About half of the patients have a deficiency of the alpha-2-chain of laminin (merosin). We describe a case of congenital muscular dystrophy in an infant with laminin-a2-chain deficiency, which appeared hypotonia in early infancy. Diagnosis was made by clinical features and the histological and immunohistochemical studies on muscle biopsy.
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PMID:[Congenital muscular dystrophy with laminin-a2 deficiency in early infancy: diagnosis and long-term follow-up]. 1616 76

Congenital muscular dystrophy (CMD) due to merosin (laminin alpha2 chain) deficiency is an autosomal recessively inherited disorder characterized by severe muscular weakness and hypotonia from birth on. Brain involvement is the rule and characterized by variable T2 hyperintensities of white matter which appears swollen on cranial MRI. The pathophysiology of these white matter changes is not clear. In five patients with laminin alpha2 deficient CMD we performed short-echo time localized proton MRS with determination of absolute metabolite concentrations in grey and white matter. In affected white matter, a consistent pattern of metabolites was detected comprising reduced concentrations of N-acetylaspartate and N-acetylaspartylglutamate, creatine, and phosphocreatine, and to a milder degree of choline-containing compounds. In contrast, concentrations of myo-inositol were in the normal range. Spectra of cortical and subcortical grey matter were normal. The observed metabolite profile is consistent with white matter edema, that is reduced cellular density, and relative astrocytosis. This interpretation is in line with the hypothesis that laminin alpha2 deficiency results in leakage of fluids across the blood-brain barrier and a histopathological report of astrocytic proliferation in CMD.
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PMID:Quantitative proton MRS of cerebral metabolites in laminin alpha2 chain deficiency. 1717 99

We report a sporadic case of congenital muscular dystrophy (CMD) in a 13-year-old girl with early manifestation of muscle weakness and hypotonia, severe contractures, bulbar syndrome, progressive external ophtalmoplegia, and white matter changes on magnetic resonance imaging (MRI) of the brain, but no mental defect. Serum creatine kinase (CK) level was normal. Muscle biopsy revealed a dystrophic picture with a prominent inflammatory infiltrate mimicking inflammatory myopathy-typical histological findings in CMD. Immunostaining showed normal expression of merosin, alpha and beta-dystroglycans. Mutation analyses of calpain3, dysferlin, and SEPN1 genes were negative. An electron microscopy revealed the accumulation of abnormally enlarged mitochondria located under the sarcolemma. Measurement of respiratory chain enzyme activities did not reveal any biochemical defect and mitochondrial genetic studies, including sequencing of the entire mitochondrial genome, were unremarkable. Phenotypic presentation of our patient is very unusual and differs considerably from other CMD variants.
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PMID:An unusual case of congenital muscular dystrophy with normal serum CK level, external ophtalmoplegia, and white matter changes on brain MRI. 1739 6

Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is the most common form of congenital muscular dystrophy. MDC1A is caused by mutation of the laminin alpha-2 gene (LAMA2), localized to chromosome 6q22-23. The diagnosis of merosin-deficient CMD is based on the clinical findings of severe congenital hypotonia, weakness, with high blood levels of creatine kinase, WM abnormalities, and dystrophy associated with negative immunostaining of biopsied muscle for merosin. We investigated clinical and laboratory a patient: a girl with merosin-deficient congenital muscular dystrophy type 1A. Clinically the particularity of the case is the association of merosin-negative congenital muscular dystrophy (MN-CMD) with congenital feet deformity. The level of serum creatine kinase is elevated 1045 U/L. Immunohistochemistry show presence of dystrophin, lack of merosin, also the utrophin is normally expressed. Nerve conduction studies are normally, while electromyography suggested a myopathic process with early recruitment and decreased amplitude and duration of response. Magnetic resonance imaging: MRI T1 and MRI T2 show hypointensity and diffuse hyperintensity respectively in the white matter. Supratentorial MRI images showed hypotrophy of the corpus callosum and almost absent cingulate gyrus. In addition, hypophysis is reduced size.
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PMID:Merosin-deficient congenital muscular dystrophy type 1A. 1851 31


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