Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Myotonic Disorders”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1979

Monovalent cation transport in myotonic dystrophy. Na-K pump ratio in erythrocytes.

Myotonic dystrophy is a dominantly-inherited disorder which affects skeletal muscle in combination with several other systems. Because of abnormalities in red blood cells, a universal membrane defect has been proposed as the primary disturbance. Erythrocyte cation pump ratios have also been reported to be abnormal. Hyperinsulinemia and glucose intolerance are present in a large number of patients. Since dramatic effects of insulin on membrane cation transport have been shown in several tissues, notably skeletal muscle, we wished first to confirm reports of altered pump ratio in these patients and then to evaluate the effects of insulin on cation fluxes. However, in our experiments myotonic dystrophy patients had normal pump ratios when compared with disease controls.

Carrier Proteins↗
PubMed1978

Metabolic implications of distal atrophy. Carbohydrate metabolism in centronuclear myopathy.

Centronuclear myopathy, like myotonic dystrophy, is characterized by muscle wasting and type 1 fiber atrophy. To determine whether this disorder might include a derangement in carbohydrate metabolism similar to that in myotonic dystrophy, 3 comparably wasted patients with centronuclear myopathy, myotonic dystrophy, and neurogenic atrophy were investigated. The patient with centronuclear myopathy had mild glucose intolerance and hypoinsulinemia after oral glucose ingestion in bold contrast to the normal glucose tolerance and hyperinsulinemia observed in the myotonic dystrophy patient. No abnormality was seen in oral glucose tolerance in the patient with neurogenic atrophy, and all 3 patients had normal insulin tolerance. Forearm insulin infusion demonstrated normal stimulation of muscle glucose uptake in the patients with centronuclear myopathy and neurogenic atrophy in contrast to the markedly diminished response to insulin seen in the patient with myotonic dystrophy. These data indicate that neither distal wasting or type 1 fiber atrophy are responsible for the abnormalities in carbohydrate metabolism in myotonic dystrophy.

Adult↗
PubMed2025

Pentatricopeptide repeat protein targeting CUG repeat RNA ameliorates RNA toxicity in a myotonic dystrophy type 1 mouse model.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder caused by the expansion of a CTG-triplet repeat in the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. It results in the transcription of toxic RNAs that contain expanded CUG repeats (CUGexp). Splicing factors, such as muscleblind-like 1 (MBNL1), are sequestered by CUGexp, thereby disrupting the normal splicing program that is essential for various cellular functions. Pentatricopeptide repeat (PPR) proteins, originally found in plants, regulate RNA in organelles by binding in a sequence-specific manner. Here, we designed PPR proteins that specifically bind to the hexamer of CUG repeat RNAs (CUG-PPRs) and showed that CUG-PPR1 could ameliorate RNA toxicity induced by CUGexp in cell models of DM1. A single systemic recombinant adeno-associated virus (AAV9) vector-mediated gene delivery of CUG-PPR1 demonstrated long-term therapeutic effects on myotonia and restored splicing activity in a mouse model of DM1. These results highlight the potential of PPR molecules to target pathogenic RNA sequences in DM1 and potentially other RNA-mediated disorders.

Animals↗
PubMed1978

Baclofen trial in six myotonic dystrophy patients.

Six young adult patients with grade I myotonic dystrophy and a complaint of daytime somnolence underwent 36-hour polygraphic monitoring, dynamometric and electromyographic studies before and under baclofen (60 mg/daily). Patients with the most severe daytime sleepiness had pathologic Sleep Apnea Indexes. After 6 weeks' ingestion of baclofen, no subjective or objective effect on patient symptomatology was found.

Adolescent↗
PubMed1975

Early onset myotonic dystrophy in association with polyneuropathy.

A patient with early onset of myotonic dystrophy, with associated neuropathy and epilepsy, is presented. It is postulated that his disorder was inherited through a recessive, pleomorphic gene. His differential diagnosis is discussed and the literature reviewed. The clinical variability of myotonic dystrophy is stressed and the diagnostic difficulties encountered in the younger age group.

Adolescent↗
PubMed2026

Generation of isogenic rescue iPSC lines by targeted CTG-repeat excision for myotonic dystrophy type 1.

An expanded CTG repeat in the Dystrophia Myotonica Protein Kinase (DMPK) gene is associated with myotonic dystrophy type 1 (DM1), an autosomal dominant neuromuscular disorder characterised by progressive muscle weakness, myotonia, cognitive decline, and a variety of other manifestations. Here, we report the generation of isogenic induced pluripotent stem cell (iPSC) lines, derived from patient DM1 iPSC lines carrying varying expanded (CTG)n repeats in DMPK. These gene-edited isogenic iPSC lines, in which the pathogenic repeat has been excised, serve as a reference for assessing DM1-associated phenotypes in relevant differentiated cell types, such as muscle progenitor cells and neurons.

Humans↗
PubMed1979

Myotonic dystrophy associated with thyroid disease.

Two patients with hereditary, clinical, electromyographical and histological data typical of myotonic dystrophy are discussed. In both there was a thyroid disorder. The first patient had primary hypothyroidism, and the second a non-toxic multinodular goiter which necessitated total thyroidectomy. The EMG findings and the muscle histopathology of both patients are commented on and compared with the changes described in hypothyroidism. The disease processes in both patients are also discussed in relation to the muscle and metabolic changes described in myotonic dystrophy. The coexistence of these two diseases is not explicable in the light of present knowledge on the basis of a known genetic predisposition. Only two similar cases of myotonic dystrophy and hypothyroidism have been reported.

Adult↗
PubMed1976

Clinical effects of myotonic dystrophy on pregnancy and the neonate.

The article describes pregnancies and labors of five women with myotonic muscular dystrophy and their four severely involved infants, and reviews the pertinent literature. Three of the four neonatal cases died by 3 weeks of age of respiratory failure or aspiration; the fourth infant is now 4 months old and has respiratory and swallowing difficulties. The symptoms of myotonic dystrophy worsen during pregnancy. A high rate of fetal loss occurs due to spontaneous abortion, prematurity, and neonatal involvement with the disease. Prolonged labor has been described as a consistent complication, but the evidence does not justify this conclusion. Although many neonates with myotonic dystrophy are asymptomatic, severely affected newborns have a recognizable disorder unrelated to the severity of the maternal disease. The most common clinical manifestations in the neonate are arthrogryposis involving predominantly the lower extremilies, generalized hypotonia and weakness, and pharyngeal weakness. Less constant features include polyhydramnios, facial diplegia, diaphragmatic paralysis, respiratory failure, decreased motility of the gastrointestinal tract, congenital cataracts, and electrocardiographic abnormalities.

Adult↗
PubMed1979

Evaluation of insulin receptor in myotonic dystrophy.

Only 2 of 6 patients with myotonic dystrophy had glucose intolerance and hyperinsulinemia. All, however, had markedly reduced insulin binding to specific receptors on circulating monocytes. A significant difference in receptor affinity for insulin was observed, but the difference in affinity was not as marked as that in the amount of 125I-insulin bound per cell, which was sixfold greater in control cells. No evidence for a circulating factor competing with insulin for binding sites could be demonstrated. These alterations in binding did not directly correlate with glucose intolerance or hyperinsulinemia and are consistent with a postulated generalized membrane defect. Study of the insulin receptor in this disorder may uncover regulatory mechanisms in normal and pathological conditions, including myotonic dystrophy.

Glucose↗
PubMed1976

Chromosome abnormalities in neurological diseases.

The current status of research into chromosomal abnormalities in neurological diseases is reviewed. The only possible association between chromosome aberration and neurological disorder is found in ataxia telangiectasia and in tumours of the nervous system. In the remaining diseases reviewed, no specific association was confirmed. This was expected to some extent, since the majority of these diseases (spinal muscular atrophies, muscular dystrophies, etc.) are due to single gene defects.

Chromosome Aberrations↗
PubMed1975

Alveolar hypoventilation and hyperosmnia in myotonic dystrophy.

A case of myotonic dystrophy accompanied by alveolar hypoventilation and hypersomnia is presented. Radiological studies and EMG examination of the intercostal muscles demonstrated that the respiratory muscles were affected by the disease, while polygraphic recordings showed that the alveolar hypoventilation and pulmonary hypertension worsened during sleep. The hypersomnia preceded the appearance of clinical signs of the muscular disease by many years and persisted even after treatment when the blood gas analysis values were greatly improved. During both diurnal and nocturnal sleep, the patient frequently fell asleep directly into a REM stage. The possibility is discussed that, concomitant with the respiratory musculature involvement, there is an alteration in the central nervous system in myotonic dystrophy which is at least partially responsible for both the alveolar hypoventilation and the hypersomnia.

Aminobutyrates↗
PubMed1978

Myotonic dystrophy: studies on the lipid composition and metabolism of erythrocytes and skin fibroblasts.

With the aim of establishing the underlying biochemical lesion in myotonic dystrophy, the lipids of plasma and of the membranes of erythrocytes and cultured skin fibroblasts were investigated in patients with this disorder and normal age- and sex-matched controls. No qualitative or quantitative differences could be detected in the lipid constituents of either plasma or erythrocytes from patients and controls. Similar growth characteristics and levels of sodium [1-14C]acetate incorporation were found in skin fibroblasts from both groups when grown in medium supplemented with either normal serum or delipidated serum. It is concluded that despite the previous evidence that drug induced myotonia results from a primary disturbance of membrane lipids, and suggestions that myotonic dystrophy might have a similar basis, our results did not support this hypothesis. They do not however exclude a primary membrane enzyme abnormality as the basic defect for the disorder.

Blood↗
PubMed1977

Absence of sleep-related growth hormone elevations in myotonic dystrophy.

There is evidence that in myotonic dystrophy, the endocrine and central nervous systems are affected. To study a possible relationship between both defects, we investigated nocturnal sleep patterns and associated growth hormone secretion in two men and three women with myotonic dystrophy. In three patients who were clinically the most severely affected by myotonic dystrophy, plasma growth hormone elevations related to the slow-wave phase of sleep were absent. The two least severely affected patients had plasma growth hormone increases of low magnitude and brief duration (from 0.4 ng per milliliter to 13.0 ng per milliliter). These data suggest a failure of integration at a subcortical level of the slow-wave phase of sleep with the hypothalamic-pituitary mechanisms of growth hormone secretion. Thalamic neuronal lesions occurring in myotonic dystrophy could be responsible for such failure.

Adult↗
PubMed1978

Abnormal iris vasculature in myotonic dystrophy. An anterior segment angiographic study.

The microvasculature of the iris was studied in 35 patients with neuromuscular disease and 14 control subjects, using anterior segment fluorescein angiography. Myotonic muscular dystrophy, in which a variety of ocular changes have previously been reported, was found to be associated with both focal and generalized vascular abnormalities. Changes were seen in the fluorescein angiograms of all nine of the myotonic dystrophy patients in which the iris vessels could be seen. No evidence of a microcirculatory disorder was seen in patients with Duchenne's dystrophy, for which a vascular pathogenesis has been proposed. The angiograms of patients with limb-girdle dystrophy, facioscapulohumeral dystrophy, and Friedreich's ataxia were also normal.

Adult↗
PubMed1979

Diaphragmatic elevation in neonatal myotonic dystrophy.

In two infants born to mothers with myotonic dystrophy, chest roentgenograms showed elevation of the right sides of the diaphragms. These findings aided in the diagnoses of the neonatal form of myotonic dystrophy and the diagnoses were confirmed at autopsy. Diaphragmatic elevation in neonatal myotonic dystrophy is important to differentiate from diaphragmatic abnormalities that may be amenable to surgery. Accurate early diagnosis and appropriate genetic counseling is important in the management of this disorder.

Adolescent↗