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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two first cousins, the offspring of consanguineous marriages, had features suggestive of Marden-Walker syndrome. Phenotypic similarities and differences for Schwartz-Jampel syndrome have been discussed. Main features of the Marden-Walker syndrome are failure to thrive, marked motor and mental retardation, and multiple malformations in the form of peculiar facies associated wilth poor muscle mass, mild congenital joint contractures, pigeon breast, kyphoscoliosis and arachnodactyly. Peculiar facies is due to blepharophimosis, congenital ptosis, hypoplastic mandible and low-set and malformed ears. Posterior median cleft of the palate as well as cardiac and renal anomalies were noted in the case reported by Marden and Walker. Our Case 2 had dextrocardia. The present report suggests autosomal recessive inheritance of this syndrome.
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PMID:Probable Marden-Walker syndrome: evidence for autosomal recessive inheritance. 122 20

We report the first Japanese female patient with Walker-Warburg syndrome. She had generalized muscle hypotonia with hydrocephalus due to Dandy-Walker malformation and bilateral microphthalmia with opaque corneas. She had severe motor and mental retardation. Muscle histology reflected advanced changes of muscular dystrophy. We discuss the relationship between Fukuyama congenital muscular dystrophy and Walker-Warburg syndrome, both of which fall within a spectrum of developmental abnormalities with a common cause. In Fukuyama congenital muscular dystrophy, ocular abnormalities are less severe.
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PMID:Walker-Warburg syndrome in a Japanese patient. 307 8

This article presents ten children with agenesis of the corpus callosum diagnosed during the period 1978-1992. The children were re-examined in 1992, and the results of the examination compared with the results of other authors. Among the ten children, five had other cerebral anomalies, six had eye anomalies, six were mentally retarded and two suffered from epilepsy. There was one boy with inversion on chromosome no. 1, one girl with Aicardie's syndrome, two sisters with agenesis of the corpus callosum (ACC), one of whom was suffering from diabetes insipidus, and two brothers with Walker Warburg's syndrome. ACC is often associated with mental retardation, epilepsy and eye anomalies and may be found associated to many different syndromes.
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PMID:[Agenesis of the corpus callosum]. 770 33

Major advances in the genetic understanding of the limb-girdle (LGMD) and congenital (CMD) muscular dystrophies have led to a new, genetically based classification of these disorders. The definition of the complex of dystrophin-associated proteins on a biochemical and subsequently genetic level has greatly accelerated this progress by providing candidate genes to complement or replace the process of linkage analysis either in families with muscular dystrophy or in sporadic cases. The major components of the dystrophin-associated proteins now known to be involved in muscular dystrophy besides dystrophin itself ar the sarcoglycan complex and the alpha 2-chain (merosin) of laminin-2 in the extracellular matrix. Mutations in the various sarcoglycans account for four types of autosomal recessive LGMD of varying severity (types 2C through 2F), including severe childhood-onset presentations. One type of autosomal recessive LGMD (type 2A) is caused by mutations in the protease calpain-3, whereas the gene for type 2B has not yet been identified, although the responsible locus has been assigned to chromosome 2p13. There are different autosomal dominant forms as well, one of which has been mapped to chromosome 5q31. With regard to CMDs, the major breakthrough involves a type of "classic" CMD with abnormalities of the white matter on magnetic resonance imaging of the brain. These patients show deficiencies of the laminin alpha 2-chain, and mutations in the corresponding gene have been identified. The group of laminin alpha 2-chain-positive classic CMD likely is heterogeneous. Among the group of CMDs with abnormalities of brain formation and mental retardation, genetic, immunohistochemical, and clinical differences are now beginning to emerge to help in the distinction between Fukuyama muscular dystrophy, the Walker-Warburg syndrome, and muscle-eye-brain disease.
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PMID:Beyond dystrophin: current progress in the muscular dystrophies. 901 40

Among the variable manifesting conditions of neuronal migration disorders, mental retardation, motor disturbance and epilepsy are the main features of developmental disabilities. We analyzed the relationship between clinical symptoms and magnetic resonance (MR) images, including surface anatomy scan (SAS). Thirty nine patients (23 males, 16 females; mean age 6.1 years) with neuronal migration disorders were studied. The diagnoses were cerebral palsy in 23 cases, mental retardation in 4. West syndrome in 4, Fukuyama type congenital muscular dystrophy (FCMD) in 6. Walker-Warburg syndrome in 1 and Dubowitz syndrome in 1. Cortical dysplasias were classified into the following 7 groups, mainly based on the SAS findings: complete agyria (AG 1), mixture of agyria and pachygyria (AG 2), bilateral complete pachygyria (BP 1), diffuse pachygyria with marked widening of the bilateral superior frontal gyrus (BP 2), unilateral pachygyria with hemispheric atrophy or hemimegalencephaly UP), focal cortical dysplasia (FP) and other findings such as solitary schizencephaly (Others). Most cases of AG 1 and AG 2 showed spastic quadriplegia (6/7) and symptomatic generalized epilepsy (5/7), whereas cases of BP1 showed spasticity only in 1/8 and epilepsy in 7/8. Hemiplegia was observed in 6/7 of UP, 2/8 of FP and 2/4 of Others. Partial epilepsy was observed in 2/7 of UP and 1/8 of FP. Intellectual level was variable in BP 1, UP, FP and Others, but all cases showed severe mental retardation in AG 1, AG 2 and BP 2. BP 2 was observed in all cases of typical FCMD (5/5). The birth weight was less than 2,500 g in 6/7 of UP. The structural findings well correlated with clinical symptoms and epileptic seizure types. The surface anatomy scan was a very useful technique for detecting cortical dysplasias.
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PMID:[The relationship between MR images and clinical findings in neuronal migration disorders]. 924 87

A heterogeneous group of patients with congenital muscular dystrophy associated with clinical or radiologic central nervous system involvement other than the severe classic form with merosin deficiency, muscle-eye-brain disease, and Walker-Warburg syndrome is described. A probable hereditary or familial occurrence could be suggested in all patients. One merosin-positive patient presented severe motor incapacity and cerebral atrophy without any clinical manifestation of central nervous system involvement. A second patient, also merosin-positive, had moderate motor and mental handicap, and epilepsy with no changes in neuroimaging. A third patient, found to have partial merosin deficiency by muscle biopsy, manifested severe psychomotor retardation and cerebral atrophy with foci of abnormal white-matter signal on magnetic resonance imaging. Finally, two merosin-positive siblings with microcephaly, mental retardation, and an incapacitating progressive neuromuscular course, exhibited cataracts without defects of neuronal migration or brain malformation. This report emphasizes the broad clinical spectrum and heterogeneity of merosin-positive congenital muscular dystrophy with associated central nervous system involvement, and illustrates the importance of further studies on clinical, immunohistochemical, and genetic grounds for identifying new subsets of congenital muscular dystrophy.
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PMID:Heterogeneity of classic congenital muscular dystrophy with involvement of the central nervous system: report of five atypical cases. 1075 73

Congenital muscular dystrophy (CMD) is one of the most frequent dystrophies of childhood, which is commonly characterized by neonatal muscle impairment with or without clinical evidence of central nervous system involvement. CMDs were classified into five clinically distinct forms: the two classical CMDs with and without deficit of the a2 laminin chain (merosin) caused by mutations on chromosome 6q2, the Fukuyama CMD (severe form, initially described in Japanese patients and recently linked to the chromosome 9q31-33), Walker-Warburg syndrome and the muscle-eye-brain disease described in Finnish patients. The majority of these forms have severe clinical and imagiological involvement of SNC. This aspect is rarely observed on classical CMD, particularly in the merosin-positive form. We describe a case of a 28 year-old woman, with clinical and histopathological signs of classical CMD merosin-positive (no deficient), without mental retardation, but with epilepsy. MRI T2 weighted images, revealed diffuse and symetrical high signal white matter of both cerebral hemispheres, affecting corpos calosum, posterior arms of internal capsules and the piramidal tract to mesencephalon. It also disclosed diffuse and symetrical high signal of basal ganglia, specially, the head of caudate nuclei. These were associated with bilateral occipital posterior cortical dysplasia. The observed imagiological pattern could represent a new subtype of CMD, hybrid between classical CMD and the severe forms, however it is not clear where it fits in the spectrum. This case denotes the possible envolvement of SNC in patients merosin-positives. Based on this findings we suggest doing MRI scans to all patients with CMD no deficient in merosin.
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PMID:[Merosin-positive congenital muscular dystrophy, white matter abnormalities, and bilateral posterior occipital cortical dysplasia]. 1286

The congenital muscular dystrophies (CMD) are a heterogeneous group of autosomal recessive disorders. A new pathomechanism has recently been identified in a group of these disorders in which known or putative glycosyltransferases are defective. Common to all these conditions is the hypoglycosylation of alpha-dystroglycan. Fukuyama CMD, muscle-eye-brain disease and Walker-Warburg syndrome, each associated with eye abnormalities and neuronal migration defects, result from mutations in fukutin, POMGnT1 and POMT1, respectively, while mutations in the fukutin-related protein (FKRP) gene cause congenital muscular dystrophy 1C, typically lacking brain involvement. Another putative glycosyltransferase, Large, is mutated in the myodystrophy mouse. The human homologue of this gene is therefore a strong candidate for involvement in novel forms of muscular dystrophy. We studied 36 patients with muscular dystrophy and either mental retardation, structural brain changes or abnormal alpha-dystroglycan immunolabelling, unlinked to any reported CMD loci. Linkage analysis in seven informative families excluded involvement of LARGE but sequencing of this gene in the remaining 29 families identified one patient with a G1525A (Glu509Lys) missense mutation and a 1 bp insertion, 1999insT. This 17-year-old girl presented with congenital muscular dystrophy, profound mental retardation, white matter changes and subtle structural abnormalities on brain MRI. Her skeletal muscle biopsy showed reduced immunolabelling of alpha-dystroglycan. Immunoblotting with an antibody to a glycosylated epitope demonstrated a reduced molecular weight form of alpha-dystroglycan that retained some laminin binding activity. This is the first description of mutations in the human LARGE gene and we propose to name this new disorder MDC1D.
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PMID:Mutations in the human LARGE gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan. 1296 29

The importance of O-glycosylation of alpha-dystroglycan (alpha-DG) is evident from the identification of POMT1 mutations in Walker-Warburg syndrome (WWS). Approximately one-fifth of the WWS patients show mutations in POMT1, which result in complete loss of protein mannosyltransferase activity. WWS patients are characterized by congenital muscular dystrophy (CMD) with severe brain and eye abnormalities. This suggests a crucial role for alpha-DG during development of these organs and tissues. Here we report new POMT1 mutations and polymorphisms in WWS patients. In addition, we report different compound heterozygous POMT1 mutations in four unrelated families that result in a less severe phenotype than WWS, characterized by CMD with calf hypertrophy, microcephaly, and mental retardation. Compared to WWS patients, these patients have milder structural brain abnormalities, and eye abnormalities were absent, except for myopia in some cases. In these patients we postulate that one or both transcripts for POMT1 confer residual protein O-mannosyltransferase activity. Our data suggest the existence of a disease spectrum of CMD including brain and eye abnormalities resulting from POMT1 mutations.
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PMID:The expanding phenotype of POMT1 mutations: from Walker-Warburg syndrome to congenital muscular dystrophy, microcephaly, and mental retardation. 1657 35

Mutations in POMT2 have so far only been reported in patients with Walker-Warburg phenotype. We report heterozygous POMT2 mutations in an a girl with a milder phenotype characterized by mental retardation, microcephaly, hypertrophy of the quadriceps and calf muscles, and structural brain changes mostly affecting the posterior fossa. Our findings suggest that, as previously reported for POMT1 and FKRP, mutations in the POMT2 can also be associated with clinical heterogeneity.
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PMID:POMT2 mutation in a patient with 'MEB-like' phenotype. 1670 95


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