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

"Classic" congenital muscular dystrophy is a heterogeneous group of disorders, characterized by early-onset muscle weakness and hypotonia, absence of overt cerebral or ocular symptoms, and muscle pathology consistent with a dystrophic process. A subset of patients with congenital muscular dystrophy have recently been found to be deficient in the extracellular matrix protein merosin. Consequently, we reviewed the clinical, pathologic, and immunohistochemical features of 12 patients (six males and six females) with classic congenital muscular dystrophy who have been seen at the Children's Hospital, Boston, over the past 15 years. There was marked clinical heterogeneity within this patient population, with age of independent ambulation ranging from 13 months to 6 years. Immunocytochemical analysis using antibodies to merosin, dystrophin, 43-kDa dystroglycan, adhalin, and laminin was normal in 11 of 12 patients. One patient had markedly abnormal staining for merosin; the majority of fibers were negative, although occasional fibers demonstrated patchy staining. Immunoblot analysis in this patient demonstrated markedly reduced levels of merosin (< 10% compared to controls and other patient), of apparently normal size. Clinically, this patient could be differentiated from the others by a marked elevation of serum creatine kinase (> 1000 U/L) and the presence of early white-matter changes on magnetic resonance imaging. The results of this study support the observation that abnormalities of merosin are present in a subgroup of patients with classic congenital muscular dystrophy. Although marked elevation of serum creatine kinase and white-matter changes on magnetic resonance imaging may serve to distinguish these patients from other patients with congenital muscular dystrophy, there remains a large proportion of patients in whom the underlying pathogenesis remains to be elucidated.
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PMID:Congenital muscular dystrophy associated with merosin deficiency. 880 18

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 on two sisters of first degree cousin parents who were born with severe hypotonia, arthrogryposis multiplex congenita (AMC) and dysmorphic features consistent with the fetal akinesia/hypokinesia sequence. They needed assisted ventilation and each died at the age of 5 months. Both had type II lissencephaly (cobblestone lissencephaly) which was visualized by magnetic resonance imaging (MRI) in the proband. Ophthalmic evaluation revealed no ocular malformations in either of them. Brain auditory evoked potentials (BAEP) revealed bilateral severe sensorineural hearing loss in the proband, whereas an MRI-guided open muscle biopsy of the sartorius muscle (the only remaining thigh muscle) showed features of muscular dystrophy. Immunohistochemistry revealed normal dystrophin, dystrophin-associated glycoproteins (DAG) and merosin. Certain clinical and pathological features distinguish the disease seen in these sisters from reported isolated cases where lethal AMC was associated with brain dysplasia and from the main syndromes of congenital muscular dystrophy/cobblestone lissencephaly. Differences from the Walker-Warburg syndrome, which simulates it in severity, included the absence of severe hydrocephalus, normal creatine kinase (for age) and minimal (mainly periventricular) white matter abnormalities. The findings suggest either an independent entity, in the studied family, or an allelic variation of the cobblestone lissencephaly (type II lissencephaly) syndrome.
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PMID:Lethal congenital muscular dystrophy in two sibs with arthrogryposis multiplex: new entity or variant of cobblestone lissencephaly syndrome? 905 48

A girl born from consanguineous Turkish parents had marked hypotonia from birth and delayed milestones. She was able to stand unaided by 3 years of age with then progressive worsening of motor abilities. She had a severe non-progressive mental deficiency. Epilepsy occurred by 6 years of age. Ophthalmological investigation was normal. A marked white matter high signal was seen on magnetic resonance imaging without cortical dysplasia. Dystrophic changes were seen on muscle biopsy. Two brothers had had a similar history with early death. Muscular immunocytochemical studies showed a normal staining for dystrophin and all dystrophin related glycoproteins (including 43 and 50 DAG). Merosin staining was normal. This case differs from Fukuyama's congenital dystrophy, from merosin negative congenital muscular dystrophy, or from other congenital muscular dystrophy with CNS dysfunction. It underlines the heterogeneity of congenital muscular dystrophy and the non-specific aspect of white matter changes on neuro-imaging.
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PMID:Merosin positive congenital muscular dystrophy with mental deficiency, epilepsy and MRI changes in the cerebral white matter. 918 83

myotonic dystrophy, also called the Curschmann-Steinert syndrome, is an autosomal dominant inherited neuromuscular disorder characterized by progressive muscular dystrophy, muscle weakness and myotonia, which can affect both mother and child. Complications may arise during pregnancy, delivery, including anaesthetic problems, and in the neonatal period. During pregnancy hydramnion can be a first sign of the disease leading to premature labor and also muscle weakness and myotonia can aggravate complicating the course of delivery. The affected neonate may display severe hypotonia, facial diplegia and respiratory distress. The clinical diagnosis can be confirmed by direct DNA analysis in serum and in chorionvillus biopsy material. In this case report two sisters with myotonic dystrophy are described, their pregnancies, deliveries and the outcome of their affected babies.
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PMID:Myotonic dystrophy in pregnancy: a report of two cases within one family. 922 95

The classical form of congenital muscular dystrophy (CMD) is now classified into merosin-deficient and -positive forms. The merosin (laminin alpha 2) is one of three subunits of a muscle basement membrane protein, laminin. Patients with the merosin-deficient form have generalized muscle weakness and hypotonia from early infancy as seen in FCMD but with no significant central nervous system involvement. The serum creatine kinase (CK) is markedly elevated. Strikingly all patients examined by a CT/ MRI have diffuse white matter abnormalities mimicking leukodystrophy. The gene has been mapped to chromosome 6q2 in the coding region for merosin. Since the responsible gene and protein have not been identified in the merosin-positive form, this CMD is probably a group of heterogeneous diseases. The overall symptoms are mild, approximately 90% of patients learned to walk alone.
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PMID:[Non-Fukuyama type congenital muscular dystrophy--merosin deficient and positive forms]. 943 31

Myotonic dystrophy (DM), the most common muscular dystrophy of adult life, presents with a variety of clinical and genetic challenges to all involved; patients, their families, and clinicians. The clinical picture is extremely variable and may range from mild adult onset myotonia to severe congenital hypotonia associated with respiratory distress. An infant born to a mother with DM had remarkable hypotonia, expressionless face, respiratory difficulties, and club feet. Direct molecular genetic testing of the newborn and the mother showed trinucleotide repeat expansion mutations. Genetic counseling issues as well as the value of prenatal diagnosis are presented.
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PMID:Clinical expression of myotonic dystrophy: the predictive role of DNA diagnosis. 950 53

This is a consecutive study on 28 patients who have been diagnosed as having congenital muscular dystrophy at Jordan University Hospital in the period from January 1990 to February 1997. Of 75 patients diagnosed as having muscle disease, 55 (73.3%) had muscular dystrophy. Of 55 muscular dystrophy patients, 28 (50.9%) had congenital muscular dystrophy, 11 (20%) had Duchenne muscular dystrophy, 9 (16.4%) had Becker muscular dystrophy, 4 (7.3%) had myotonic dystrophy, 2 (3.6%) had limb-girdle dystrophy, and 1 (1.8%) patient had facioscapulohumeral dystrophy. Age of onset of symptoms of congenital muscular dystrophy (hypotonia and weakness) was documented antenatally or in the first few months in the majority (92.9%) of patients. Parental consanguinity was documented in 21 (75%) of congenital muscular dystrophy cases, and family history of possible similar cases in 15 (53.6%). Congenital muscular dystrophy patients with normal cognitive milestones (n = 16; 57.1%) were slightly more common than patients with cognitive delay. In contrast to previous reports, congenital muscular dystrophy is probably more common in communities with high rates of parental consanguinity than other dystrophies. Our study adds significant support to the most recent literature on this finding.
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PMID:Congenital muscular dystrophy in Jordanian children. 972 93

It has been suggested that patients with autosomal recessive merosin deficient congenital muscular dystrophy (CMD), as opposed to the merosin positive cases form a homogeneous subgroup of a clinically more severe form of CMD. We examined merosin expression in muscle biopsies from five children with the severe classical form of CMD. Merosin deficiency was found only in 1 patient, a 6-year-old female, with abnormal brain myelination. However, her initial biopsy did not reveal the classical picture of dystrophy. The four merosin positive cases exhibited severe muscle weakness but their brain imagings were normal. There were no familial cases, except for the mother of 1 patient who had a milder form of the disease, suggesting an autosomal dominant mode of inheritance. In contrast to previous reports, the merosin deficient CMD cases were rare in our group. Furthermore, merosin positive cases were also associated with severe phenotype suggesting that a severe phenotype is not exclusive to merosin deficient cases. Finally, the absence of merosin in a neonate with hypotonia and weakness can be helpful in making a definitive diagnosis of CMD, even though the dystrophic process may not be evident yet and histology may be non-specific.
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PMID:Severe classical congenital muscular dystrophy and merosin expression. 978 20

The congenital muscular dystrophies are a heterogeneous, recessively inherited group of disorders that have been subclassified on the basis of clinical central nervous system involvement. We report two children with "pure" congenital muscular dystrophy, one merosin negative and one merosin positive with extensive white matter and occipital cortical neuromigration abnormalities on magnetic resonance imaging (MRI). The first patient (merosin-negative congenital muscular dystrophy) presented with hypotonia and weakness in the neonatal period and subsequently was found to have a leukoencephalopathy and occipital cortical dysplasia on magnetic resonance imaging. The second patient presented with developmental delay without definite weakness. Initial investigations revealed a leukoencephalopathy and cortical dysplasia, but the patient subsequently was shown to have merosin-positive congenital muscular dystrophy. These patients illustrate that white-matter changes are not specific for merosin-negative congenital muscular dystrophy alone and that extensive cortical abnormality can be found in both groups of patients. In addition, our second patient illustrates a nonmuscular mode of congenital muscular dystrophy presentation that should be considered in patients with a "nonprogressive leukodystrophy."
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PMID:Congenital muscular dystrophy, white-matter abnormalities, and neuronal migration disorders: the expanding concept. 979 53


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