Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 38-yr-old man with external ophthalmoplegia, cardiac conduction abnormalities, hearing loss, and ragged-red fibres in skeletal muscle biopsy, developed severe signs of cardiac failure within a few months. Echocardiography and angiography demonstrated a dilated cardiomyopathy. Ubiquinone 140 mg day-1 did not stop the worsening of the cardiac status and cardiac transplantation was performed. Molecular analysis showed a heteroplasmic 4.5 kb mitochondrial DNA deletion in endomyocardial tissue. Eighteen months later, cardiac evolution is good and neurological status is stable.
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PMID:Cardiac transplantation in an incomplete Kearns-Sayre syndrome with mitochondrial DNA deletion. 818 12

A 27-year-old man was admitted to hospital because of severe cardiac failure. Investigation revealed dilated cardiomyopathy with a left ventricular ejection fraction of 15-20%. During adolescence the patient had been investigated for growth retardation and he also had progressive external ophthalmoplegia. There had been no symptoms of cardiac disease until 2 weeks before admittance. An endomyocardial biopsy showed cardiomyocytes deficient in cytochrome c oxidase (COX) in a mosaic pattern. A skeletal muscle biopsy showed mitochondrial myopathy with COX-deficient ragged-red fibers. Molecular genetic analysis revealed a heteroplasmic, 3.8-kb, mitochondrial DNA (mtDNA) deletion in heart and muscle. PCR-based quantification of the proportion of mtDNA with deletion showed 47% mutated mtDNA in the myocardial biopsy and 68% in muscle. In spite of treatment, the condition deteriorated and the patient died 5 days after admittance. This case demonstrates that mtDNA deletions may occasionally be the cause of severe dilated cardiomyopathy, and that morphological and molecular genetic diagnosis may be obtained by endomyocardial biopsy.
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PMID:Fatal dilated cardiomyopathy associated with a mitochondrial DNA deletion. 1111 Nov 48

Mutations in mitochondrial genes encoded by both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) genes have been implicated in a wide range of neuromuscular diseases. MtDNA base substitution and rearrangement mutations generally inactivate one or more tRNA or rRNA genes and can cause myopathy, cardiomyopathy, cataracts, growth retardation, diabetes, etc. nDNA mutations can cause Leigh syndrome, cardiomyopathy, and nephropathy, due to defects in oxidative phosphorylation (OXPHOS) enzyme complexes; cartilage-hair hypoplasia (CHH) and mtDNA depletion syndrome, through defects in mitochondrial nucleic acid metabolism; and ophthalmoplegia with multiple mtDNA deletions, caused by adenine nucleotide translocator-1 (ANT1) mutations. Mouse models have been prepared that recapitulate a number of these diseases. The mtDNA 16S rRNA chloramphenicol (CAP) resistance mutation was introduced into the mouse female germline and caused cataracts and rod and cone abnormalities in chimeras and neonatal lethal myopathy and cardiomyopathy in mutant animals. A mtDNA deletion was introduced into the mouse germline and caused myopathy, cardiomyopathy, and nephropathy. Conditional inactivation of the nDNA mitochondrial transcription factor (Tfam) gene in the heart resulted in neonatal lethal cardiomyopathy, while its inactivation in the pancreatic beta-cells caused diabetes. The ATP/ADP ratio was implicated in mitochondrial diabetes through transgenic modification of the beta-cell ATP-sensitive K(+) channel (K(ATP)). Mutational inactivation of the mouse Ant1 gene resulted in myopathy, cardiomyopathy, and multiple mtDNA deletions in association with elevated reactive oxygen species (ROS) production. Inactivation of uncoupler proteins (Ucp) 1-3 revealed that mitochondrial Delta Psi regulated ROS production. The role of mitochondrial ROS toxicity in disease and aging was confirmed by inactivating glutathione peroxidase (GPx1), resulting in growth retardation, and by total and partial inactivation of Mn superoxide dismutase (MnSOD; Sod2), resulting in neonatal lethal dilated cardiomyopathy and accelerated apoptosis in aging, respectively. The importance of mitochondrial ROS in degenerative diseases and aging was confirmed by treating Sod2 -/- mice and C. elegans with catalytic antioxidant drugs.
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PMID:Mouse models for mitochondrial disease. 1157 27

Cardiomyopathy and neuromuscular abnormalities may simultaneously coexist and present with defects in mitochondrial DNA and bioenergetic function. We sought to evaluate the relationship between clinical and mitochondrial phenotypes in 28 young patients with both cardiomyopathy and neurologic disorders including seizures, dystonia, ophthalmoplegia, Kearns-Sayre syndrome, Leigh disease, and Friedreich's ataxia. All tissues examined displayed marked defects in respiratory complex activities. Five patients had abundant large-scale mitochondrial DNA deletions and one patient displayed a pathogenic point mutation previously reported with mitochondrial cytopathy. In this cohort, patients with hypertrophic cardiomyopathy displayed a higher incidence of complex I defects, fewer DNA deletions and mitochondrial structural abnormalities and were less often associated with developmental delay phenotype compared with patients with dilated cardiomyopathy. Although structural abnormalities are present in a subset of patients, evaluation of respiratory enzyme activity appears to be most informative whether tissues examined were derived from heart or skeletal muscle. Defects in mitochondrial DNA and bioenergetics are frequently present in children with cardiomyopathy presenting with a variety of neurologic abnormalities and are amenable to biochemical and molecular analysis.
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PMID:Cardiomyopathy associated with neurologic disorders and mitochondrial phenotype. 1254 31

Hereditary myosin myopathies have emerged as a new group of muscle diseases with highly variable clinical features and onset during fetal development, childhood or adulthood. They are caused by mutations in skeletal muscle myosin heavy chain (MyHC) genes. Mutations have been reported in two of the three MyHC isoforms expressed in adult limb skeletal muscle: type I (slow/beta-cardiac MyHC; MYH7) and type IIa (MYH2). The majority of more than 200 dominant missense mutations in MYH7 are associated with hypertrophic/dilated cardiomyopathy without signs or symptoms of skeletal myopathy. Several mutations in two different parts of the slow/beta-cardiac MyHC rod region are associated with two distinct skeletal myopathies without cardiomyopathy: Laing early onset distal myopathy and myosin storage myopathy (MSM). However, early onset distal myopathy and MSM caused by MYH7 mutations may also occur together with cardiomyopathy. MSM affects proximal or scapuloperoneal muscles whereas Laing distal myopathy primarily affects the dorsiflexor muscles of the toes and ankles. MSM is morphologically characterized by subsarcolemmal accumulation of myosin in type 1 fibers, whereas Laing distal myopathy is associated with variable and unspecific muscle pathology, frequently with hypotrophic type 1 muscle fibers. A myopathy associated with a specific mutation in MYH2 is associated with congenital joint contractures and external ophthalmoplegia. The disease is mild in childhood but may be progressive in adulthood, with proximal muscle weakness affecting ambulation. Mutations in embryonic MyHC (MYH3) and perinatal MyHC (MYH8), which are myosin isoforms expressed during muscle development, are associated with distal arthrogryposis syndromes with no or minor muscle weakness. Clinical findings, muscle morphology and molecular genetics in hereditary myosin myopathies are summarized in this review.
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PMID:Hereditary myosin myopathies. 1743 5

Hereditary myosin myopathies are a newly emerged group of diseases caused by mutations in skeletal muscle myosin heavy chain (MyHC) genes. The phenotypes of these diseases are varied, ranging from prenatal nonprogressive arthrogrypotic syndromes to adult-onset progressive muscle weakness. They are caused by mutations in skeletal muscle myosin heavy chain (MyHC) genes. Mutations have been reported in two of three MyHC isoforms expressed in adult limb skeletal muscle: type I (slow/beta-cardiac MyHC; MYH7) and type IIa (MYH2). Most of the mutations described in MYH7are associated with hypertrophic/dilated cardiomyopathy, with no skeletal muscle involvement. However, some mutations are associated with two distinct skeletal myopathies, namely Laing distal myopathy and myosin storage myopathy. Although initially thought not to have associated cardiac involvement, recent reports have indicated co-existent cardiac and skeletal muscle disease can occur in both. A myopathy associated with a specific mutation in MYH2 is associated with congenital joint contractures and external ophthalmoplegia. Mutations in embryonic MyHC (MYH3) and perinatal MyHC (MYH8) are associated with distal arthrogryposis syndromes with no or minor muscle weakness. This may be expected in myosin isoforms expressed predominantly during muscle development. Clinical findings, muscle morphology and molecular genetics in hereditary myosin myopathies are summarized in this chapter.
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PMID:Thick filament diseases. 1918 Oct 95

The prognosis of progressive ophthalmoplegia in patients with large-scale mitochondrial DNA deletions is highly variable and almost unpredictable. The risk to develop cardiac involvement and sudden cardiac death is strikingly high, especially in patients with Kearns-Sayre syndrome (KSS). The most typical cardiac complications of the disease are conduction defects, which usually begin with left anterior fascicular block with or without right bundle branch block (RBBB), progressing sometimes rapidly to complete atrioventricular block. Other cardiac manifestations reported are first or second degree of AV block, QT prolongation, torsades de pointes ventricular tachycardia, and rarely dilated cardiomyopathy. Most frequently syncope, sometimes even sudden cardiac death, is the first clinical sign of the cardiac disease in KSS. Due to these life-threatening cardiac conditions, patients should be carefully monitored for cardiac signs and symptoms and pacemaker implantation should be suggested early to avoid sudden cardiac arrest in KSS.Here, we present two cases of KSS with life-threatening syncope due to complete atrioventricular block. To emphasize the importance of an early pacemaker implantation, we review the literature on cardiac complications in KSS in the last 20 years. In almost all of the reviewed cases, ophthalmoplegia or ptosis was present before the cardiac manifestations. In most of the cases, syncope was the first symptom of the cardiac involvement. There was no correlation between the age of the onset of the disease and the onset of cardiac manifestations.With our current report, we increase awareness for life-threatening cardiac complications in patients with KSS.
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PMID:Cardiac arrest in kearns-sayre syndrome. 2343 Aug 46