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)

We studied several affected and one nonaffected individuals belonging to three unrelated pedigrees. The pathological trait was an autosomal dominant mitochondrial myopathy due to large-scale multiple deletions of the mitochondrial genome. Clinically, symptomatic patients had progressive external ophthalmoplegia, muscle weakness and wasting, sensorineural hypoacusia, and, in some cases, vestibular areflexia and tremor. The muscle biopsies of all patients examined showed ragged-red fibers, neurogenic changes, and a partially decreased histochemical reaction to cytochrome c oxidase. Multiple mtDNA heteroplasmy was detected in the patients by both Southern blot analysis and PCR amplification, whereas the unaffected individual had the normal homoplasmic hybridization pattern. These findings confirm and add further details to the existence of a new human disease--defined clinically as a mitochondrial myopathy, genetically as a Mendelian autosomal dominant trait, and molecularly by the accumulation of multiple, large-scale deletions of the mitochondrial genome--that is due to impaired nuclear control during mtDNA replication.
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PMID:Nucleus-driven multiple large-scale deletions of the human mitochondrial genome: a new autosomal dominant disease. 197 58

A 19-year-old man born with thyroprivic hypothyroidism, due to congenital development defect, manifested hypogonadism, stunted growth, chronic progressive external ophthalmoplegia (CPEO), diffuse muscle weakness and wasting, right bundle branch block, cerebral atrophy. Muscle biopsy showed mitochondrial abnormalities. Biochemical investigations on muscle disclosed partial (50%) cytochrome c oxidase deficiency, 58% decrease of cytochrome aa3 and 41% decrease of cytochrome b. Enzyme-linked immunosorbent assay showed decrease of the immunologically active enzyme protein.
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PMID:Endocrine involvement in mitochondrial encephalomyopathy with partial cytochrome c oxidase deficiency. 254 Feb 84

A progressive neuromuscular syndrome developed in a girl suffering from fatal familial intrahepatic cholestasis (Byler disease). The neuromuscular syndrome included muscular wasting of the legs, pes cavus, areflexia, decreased vibratory sensation, cerebellar symptoms, ophthalmoplegia, and visual disturbance with retinitis pigmentosa. The serum vitamin E level was extremely low. Postmortem neuropathologic study revealed the following lesions: (1) Systemic axonopathy involving the peripheral nerves and proximal axons of the dorsal root ganglia and posterior roots as well as the distal axons of the central nervous system (CNS) (2) Neuronal loss in the sensory and oculomotor nuclei of the brain stem, basal ganglia, Clarke's column, posterior horn, and dorsal root ganglia. (3) Neuronal lipofuscinosis. Axonopathy was severer in the more distal axonal segments, although the cuneate fasciculus was more affected than the gracile fasciculus. The severity of neuronal lipofuscinosis was not correlated with that of neuronal disintegration. The electron-dense bodies in the dystrophic swollen axons resembled lipofuscin granules. These neuropathologic lesions were considered to be the sequelae to chronic vitamin E deficiency.
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PMID:Neuropathology of chronic vitamine E deficiency in fatal familial intrahepatic cholestasis. 715 98

Sixteen members of a family with a history of autosomal dominant progressive external ophthalmoplegia (adPEO) with hypogonadism were examined. The muscular involvement commenced cranially and descended in relation to increasing disease duration. The neuromuscular signs were PEO, dysarthria, dysphonia, limb muscle weakness with wasting, absence of Achilles tendon reflexes, and distal vibration sensory loss. The electromyogram (EMG) was myopathic in facial and proximal limb muscles. Neurogenic involvement was suspected in a few tibial anterior muscles. Neurography showed signs of axonal neuropathy correlated to clinical signs. F-responses were reduced in number or absent in peroneal nerves, and did not correlate to clinical signs or disease duration. Muscle biopsies in advanced cases had structural abnormalities of mitochondria, ragged-red fibers, and focal cytochrome c oxidase deficiency. A combination of muscle-nerve involvement with PEO, Achilles tendon areflexia, distal vibration sensory impairment, myopathic EMG, and abnormally low sural nerve responses seems to be typical of this type of mitochondrial disorder.
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PMID:Muscle-nerve involvement in autosomal dominant progressive external ophthalmoplegia with hypogonadism. 860 26

In a 33-year-old man, mitochondriopathy was diagnosed upon short stature, auditory impairment, gynaecomastia, hypogonadism, vertical ophthalmoplegia, cerebral atrophy, leucencephalopathy, cataract, hypertrabeculated left ventricle, hypothyroidism, diabetes mellitus, glomerulonephritis necessitating kidney transplantation, general wasting, polyneuropathy, abnormally high lactate levels on exercise, partially reduced cytochrome-c oxidase staining and abnormally structured mitochondria on muscle biopsy. Mitochondrial DNA (mtDNA) analysis revealed 1 novel (A15662G) and 3 known mtDNA transition(s) (T3398C, T4216C, G15812A) affecting the cytb and ND1 gene, respectively. Three of the patient's transitions were also detected in blood leukocytes of the patient's maternal grandmother, mother and brother. Mutant mtDNA was heteroplasmic at >75% in the patient's skeletal muscle.
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PMID:Complex mitochondriopathy associated with 4 mtDNA transitions. 1089 93

Multi-minicore Disease (MmD) is a recessively inherited neuromuscular disorder characterized by multiple cores on muscle biopsy and clinical features of a congenital myopathy. Prevalence is unknown. Marked clinical variability corresponds to genetic heterogeneity: the most instantly recognizable classic phenotype characterized by spinal rigidity, early scoliosis and respiratory impairment is due to recessive mutations in the selenoprotein N (SEPN1) gene, whereas recessive mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been associated with a wider range of clinical features comprising external ophthalmoplegia, distal weakness and wasting or predominant hip girdle involvement resembling central core disease (CCD). In the latter forms, there may also be a histopathologic continuum with CCD due to dominant RYR1 mutations, reflecting the common genetic background. Pathogenetic mechanisms of RYR1-related MmD are currently not well understood, but likely to involve altered excitability and/or changes in calcium homeoestasis; calcium-binding motifs within the selenoprotein N protein also suggest a possible role in calcium handling. The diagnosis of MmD is based on the presence of suggestive clinical features and multiple cores on muscle biopsy; muscle MRI may aid genetic testing as patterns of selective muscle involvement are distinct depending on the genetic background. Mutational analysis of the RYR1 or the SEPN1 gene may provide genetic confirmation of the diagnosis. Management is mainly supportive and has to address the risk of marked respiratory impairment in SEPN1-related MmD and the possibility of malignant hyperthermia susceptibility in RYR1-related forms. In the majority of patients, weakness is static or only slowly progressive, with the degree of respiratory impairment being the most important prognostic factor.
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PMID:Multi-minicore Disease. 1763 Oct 35

Tolosa-Hunt syndrome is an idiopathic inflammatory process of the cavernous sinus or orbit manifesting as painful ophthalmoplegia. In this report, we detail the case of a 6-year-old boy who presented with several weeks of unilateral headache and diplopia. He was found to have an infiltrative process involving the bilateral cavernous sinuses and pituitary gland on MRI. Given a progressing infiltrative central nervous system process on repeat MRI and the development of cerebral salt wasting, a biopsy was performed revealing actinomycosis. To our knowledge, this is the first reported case of actinomycosis masquerading as Tolosa-Hunt syndrome in a child.
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PMID:Actinomycosis Mimicking Tolosa-Hunt Syndrome in a 6-Year-Old Boy: Case Report. 2707 Sep 54

Neurofibromatosis type 2 usually presents with bilateral acoustic schwannomas. We highlight the rare presentation of neurofibromatosis initially involving third nerve. A 23-year-old Malay female presented with left eye drooping of the upper lid and limitation of upward movement for 8 years. It was associated with right-sided body weakness, change in voice, and hearing disturbance in the right ear for the past 2 years. On examination, there was mild ptosis and limitation of movement superiorly in the left eye. Both eyes had posterior subcapsular cataract. Fundoscopy showed generalised optic disc swelling in both eyes. She also had palsy of the right vocal cord, as well as the third and eighth nerve. There was wasting of the distal muscles of her right hand, with right-sided decreased muscle power. Pedunculated cutaneous lesions were noted over her body and scalp. MRI revealed bilateral acoustic and trigeminal schwannomas with multiple extra-axial lesions and intradural extramedullary nodules. Patient was diagnosed with neurofibromatosis type 2 and planned for craniotomy and tumour debulking, but she declined treatment. Neurofibromatosis type 2 may uncommonly present with isolated ophthalmoplegia, so a thorough physical examination and a high index of suspicion are required to avoid missing this condition.
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PMID:Neurofibromatosis Type 2 Presenting with Oculomotor Ophthalmoplegia and Distal Myopathy. 2773 38

Myasthenia gravis (MG) is a relatively uncommon disorder with an annual incidence of approximately 7 to 9 new cases per million. The prevalence is about 70 to 165 per million. The prevalence of the disease has been increasing over the past five decades. This is thought to be due to better recognition of the condition, aging of the population, and the longer life span of affected patients. MG causes weakness, predominantly in bulbar, facial, and extra-ocular muscles, often fluctuating over minutes to weeks, in the absence of wasting, sensory loss, or reflex changes. The picture of fluctuating, asymmetric external ophthalmoplegia with ptosis and weak eye closure is virtually diagnostic of myasthenia. We report an atypical MG case with three semiological cardinal signs.
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PMID:Anti-Musk Positive Myasthenia Gravis and Three Semiological Cardinal Signs. 2821 68

Congenital Fibrosis of the Extra Ocular Muscles1 (CFEOM1) is an autosomal dominant condition, caused by mutation in the KIF21A and TUBB3. It is characterized by congenital non-progressive restrictive ophthalmoplegia and ptosis. Mutational analysis of the known genes in such rare diseases by Sanger sequencing not only prevents wasting the time and expenses but also speeds diagnosis process, genetic counseling, and the possibility of prenatal diagnosis. Here, for the first time, association of pathogenic variant c.2860C>T in KIF21A gene in an Iranian family with positive history of CFEO-M1A was reported.
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PMID:KIF21A Gene c.2860C>T Mutation in CFEOM1A: The First Report from Iran. 3055 64


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