Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fukuyama-type congenital muscular dystrophy is an autosomal recessive disorder prevalent in Japan that is characterized by congenital muscular dystrophy, cobblestone lissencephaly, and eye anomalies. We examined 46 patients with Fukuyama-type congenital muscular dystrophy and followed their progress for more than 3 years, with special reference to long-term prognosis of seizure disorders and the relationship between seizures and neuropathologic abnormalities. Seizures were observed in 37 patients (80%). The average age at onset was 3 years, 1 month. Initial seizures usually occurred after a febrile episode, although one third of patients had afebrile seizures from the onset. All patients had generalized tonic-clonic convulsions at febrile disorders, and these were followed by complex partial seizures or secondary generalized seizures. Later these seizures developed into Lennox-Gastaut syndrome in three patients. Electroencephalography (EEG) showed paroxysmal discharges in 22 of 37 patients with seizures (59%). The main focus was in the frontal, temporal, or central region. Lesions with marked cortical dysplasia detected by computed tomography, magnetic resonance imaging, or autopsy showed focal paroxysmal discharges on EEG.
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PMID:Long-term prognosis of epilepsies and related seizure disorders in Fukuyama-type congenital muscular dystrophy. 1592 Dec 43

Muscle-eye-brain disease (MEB) is an autosomal recessive congenital muscular dystrophy with ocular abnormalities and type II lissencephaly. MEB is caused by mutations in the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase (POMGnT1) gene on chromosome 1q33. POMGnT1 is a glycosylation enzyme that participates in the synthesis of O-mannosyl glycan. The disease is characterized by altered glycosylation of alpha-dystroglycan. The clinical spectrum of MEB phenotype and POMGnT1 mutations are significantly expanded. We would like to present two cases with MEB disease with POMGnT1 mutations, whose clinical picture shows heterogeneity. The patient with R442H mutation had the classical form of the disease although the one with IVS17-2A-->G homozygous mutation had severe autistic features as the dominating presenting sign. These two cases represent different spectrums of one disorder. To the best of our knowledge, autistic features and stereotypical movements have not been included thus far as a part of broad and heterogeneous MEB spectrum.
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PMID:Clinical spectrum of muscle-eye-brain disease: from the typical presentation to severe autistic features. 1593 69

We describe a postnatally diagnosed case of Walker-Warburg syndrome--a form of congenital muscular dystrophy with lissencephaly and eye abnormalities. We reviewed the literature to highlight its clinico-radiological diagnostic features and discuss the difficulties encountered with prenatal diagnosis, especially in cases with no positive family history. An increased awareness of this rare but lethal condition, and a high index of suspicion during routine antenatal ultrasound, could prompt further advanced fetal ultrasonography and magnetic resonance imaging, and aid in timely prenatal diagnosis, management, and counseling.
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PMID:Difficulties with prenatal diagnosis of the Walker-Warburg syndrome. 1633 49

Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), and muscle-eye-brain (MEB) disease are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. We identified the gene for FCMD and MEB, which encodes the fukutin protein and the protein O-linked mannose beta1, 2-N-acetylglucosaminyltransferase (POMGnT1), respectively. Recent studies have revealed that posttranslational modification of alpha-dystroglycan is associated with these congenital muscular dystrophies with brain malformations. All are characterized by hypoglycosylated alpha-dystroglycan. Fukutin's function and the relation with other alpha-dystroglycanopathies are discussed.
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PMID:Fukutin and alpha-dystroglycanopathies. 1655 Sep 16

Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital muscular dystrophy associated with brain and eye abnormalities. WWS has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years. WWS presents at birth with generalized hypotonia, muscle weakness, developmental delay with mental retardation and occasional seizures. It is associated with type II cobblestone lissencephaly, hydrocephalus, cerebellar malformations, eye abnormalities and congenital muscular dystrophy characterized by hypoglycosylation of alpha-dystroglycan. Several genes have been implicated in the etiology of WWS, and others are as yet unknown. Several mutations were found in the Protein O-Mannosyltransferase 1 and 2 (POMT1 and POMT2) genes, and one mutation was found in each of the fukutin and fukutin-related protein (FKRP) genes. Laboratory investigations usually show elevated creatine kinase, myopathic/dystrophic muscle pathology and altered alpha-dystroglycan. Antenatal diagnosis is possible in families with known mutations. Prenatal ultrasound may be helpful for diagnosis in families where the molecular defect is unknown. No specific treatment is available. Management is only supportive and preventive.
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PMID:Walker-Warburg syndrome. 1688 26

Walker Warburg syndrome (WWS) is the most severe of a group of multiple congenital disorders known as lissencephaly type II ( LIS Type II) associated with congenital muscular dystrophy and eye abnormalities. The POMT1 gene is the most frequently affected found in 20% of patients with WWS. We describe five fetuses with WWS in three non-related families carrying a same mutation in the POMT1 gene. All fetuses presented with tetra ventricular hydrocephaly, and arachnoidal neuroglial ectopia and cortical dysplasia characteristic of LIS type II. We performed sequencing of the POMT1 gene on fetal DNA. The five fetuses were found to share an insertion of an inversed Alu repeated DNA element within exon 3 of the POMT1 gene, all at the heterozygous state except one at the homozygous state. This mutation was associated with a common transition c.2203 C > T (p.Arg735Cys) in exon 20 on the same allele and similar intragenic haplotype, suggesting that the three families could be related or indicating a possible founder effect in France. Insertions of Alu sequences, which are rarely found in coding regions, have occasionally been reported to cause other genetic diseases. However, this is the first report of a retrotransposon insertion in the POMT1 gene associated with WWS.
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PMID:Detection of an Alu insertion in the POMT1 gene from three French Walker Warburg syndrome families. 1707 74

Walker--Warburg syndrome (WWS), the most severe alpha-dystroglycanopathy, is characterized by brain and eye anomalies, and congenital muscular dystrophy (CMD). So far at least four genes (POMT1, POMT2, Fukutin, and FKRP gene) have been implicated in WWS, accounting for about 30% of all cases. We report a male patient with WWS resulting from a homozygous nonsense mutation (R514X) in the POMT1 gene. The patient had congenital hydrocephalus which was detected at 29 weeks of gestation. A brain MRI obtained after birth revealed type II lissencephaly, hydrocephalus, and pontocerebellar hypoplasia. The case also exhibited severe ocular malformations and muscular hypotonia due to CMD.
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PMID:A case of Walker-Warburg syndrome resulting from a homozygous POMT1 mutation. 1716 65

The Walker-Warburg syndrome is a rare and lethal autosomal recessive disorder. We report a newborn male infant with the Walker-Warburg syndrome. He had typical clinical features, including lissencephaly, congenital muscular dystrophy and an ocular abnormality associated with cleft lip and palate without hydrocephalus.
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PMID:The Walker-Warburg syndrome with cleft lip and palate. 1730 84

Muscle-eye-brain (MEB) disease is an autosomal recessive disorder characterized by a broad clinical spectrum including congenital muscular dystrophy, ocular abnormalities, and brain malformation (type-II lissencephaly). Herein, we report on two Turkish siblings with a homozygous mutation in the POMGnT1 gene. A 6-year-old sibling has a severe form of MEB disease, which in some aspects is more suitable with the diagnosis of Walker-Warburg syndrome. However, the same mutation resulted in a less severe form of MEB in the older sibling, who is 14 years old. These two cases suggest that POMGnT1 mutations may cause MEB disease with different phenotypes even in the same family.
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PMID:Severe muscle-eye-brain disease is associated with a homozygous mutation in the POMGnT1 gene. 1788 Dec 66

Muscle-eye-brain disease (MEB, OMIM 253280) is an autosomal recessive disorder characterized by a distinct triad of congenital muscular dystrophy, structural eye abnormalities, and cobblestone lissencephaly. Clinically, MEB patients present with early onset muscular hypotonia, severely compromised motor development, and mental retardation. Magnetic resonance imaging reveals a lissencephaly type II with hypoplasia of the brainstem and cerebellum. MEB is associated with mutations in the gene for protein O-mannose beta-1,2-N-acetylglucosaminyltransferase (POMGnT1, OMIM 606822). In this paper, we report the clinical findings of nine MEB patients from eight families. Eight of the nine patients presented typical features of MEB. However, a broad phenotypic variability was observed, ranging from two patients with severe autistic features to another patient with an unusually mild phenotype, initially diagnosed as congenital muscular dystrophy. Furthermore, severe hydrocephalus was reported in two families during a previous pregnancy, emphasizing the phenotypic overlap with Walker-Warburg syndrome. In addition to three previously reported mutations, we identified six novel POMGnT1 mutations (one missense, five truncating) in the present patient cohort. Our data suggest mutational hotspots within the minimal catalytic domain at arginine residue 442 (exon 16) and in intron 17. It is interesting to note that all mutations analyzed so far result in a complete loss of enzyme activity. Therefore, we conclude that the type and position of the POMGnT1 mutations are not of predictive value for the clinical severity. This supports the notion that additional environmental and/or genetic factors may contribute to the observed broad spectrum of POMGnT1-associated phenotypes.
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PMID:Novel POMGnT1 mutations define broader phenotypic spectrum of muscle-eye-brain disease. 1790 81


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