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Results for “Myotonic Disorders”

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At least 19 recordsLinked to original sources
PubMed2026

Treatment updates in myotonic disorders.

Myotonia is delayed muscle relaxation after forceful contraction. It is due to hyperexcitability of the skeletal muscle membrane. It can arise from primary skeletal muscle ion channel dysfunction, involving chloride or sodium channels, but is also a prominent clinical feature in myotonic dystrophies where altered RNA splicing leads to secondary ion channel dysregulation amongst other systemic manifestations. Clinically, myotonia can range from delayed eye opening to a disabling symptom causing impaired mobility, functional difficulty and sometimes pain. It can also be a "hidden disability" with many patients feeling socially embarrassed by "looking healthy", yet being unable to do everyday physical tasks or to do them as effortlessly as their peers. It is a symptom that almost always indicates a genetic diagnosis, although it can occur in acquired conditions, including metabolic and drug-induced causes. To experience myotonia without knowing what it is can be baffling. To receive a genetic diagnosis associated with it can be life changing. Although there is no cure, there are many effective and available symptomatic treatments for myotonia and currently we are in an exciting era of clinical trials for new molecular disease-modifying therapies for myotonic dystrophy type 1. In this review, we consider recent developments in the treatment of myotonic disorders and how they may change clinical practice.

Humans↗
PubMed1975

Study of sensitivity to curare in certain neurological disorders using a regional technique.

A regional technique for the study of curare sensitivity has been applied to patients with Duchenne type muscular dystrophy, myotonic disorders, certain lower motor neurone disorders, to patients with weakness in the arm after hemiplegia, to patients with hyper-reflexia and hypertonia without weakness, and to Parkinsonism. In the dystrophy patients, sensitivity to curare differs from normal controls in that the neuromuscular block persists. The possibilities that this latent defect of neuromuscular transmission is the result of acetylcholine deficiency due to a prejunctional defect or the result of alterations in the property of the postjunctional membrane are discussed. In the myotonic and lower motor neurone disorders, curare sensitivity was similar to that of normal controls. After hemiplegia, the affected side shows resistance to curare when compared with the unaffected side. In states of hyper-reflexia and hypertonia, however, the sensitivity to curare is greater than in normal controls. In Parkinsonism, sensitivity is similar to that of the controls. The results in upper motor neurone lesions are discussed in relation to the dependence of neuromuscular transmission upon the motor neurone, which, in turn, is dependent upon descending impulses.

Action Potentials↗
PubMed1979

Myopathies.

This paper reviews the recent advances in our knowledge of muscle disease. The use of muscle biopsy for diagnosis is discussed. The etiology, pathogenesis, and treatment of polymyositis/dermatomyositis are considered. The author discusses the clinical patterns, inheritance, and pathogenesis of progressive muscular dystrophies, especially Duchenne muscular dystrophy; myotonic disorders; glycogen storage diseases; disorders of lipid metabolism; mitochondrial diseases; and congenital muscle diseases. (Neurosurgery, 5: 747--758, 1979).

Dermatomyositis↗
PubMed1977

Weakness in myotonic syndromes.

Muscle weakness occurs in a number of myotonic syndromes, including those in which muscle bulk is preserved. The possible causes of muscle weakness may be considered in terms of the different stages of the electromechanical activation process and defects in the contractile machinery. In individual myotonic disorders the ability to identify the origin of the muscle weakness (whether neurogenic or myogenic) and the functional level at which the defect occurs would assist the choice of rational treatment.

Action Potentials↗
PubMed1977

The declining electrical response of muscle to repetitive nerve stimulation in myotonia.

The electrical response of muscle to repetitive nerve stimulation was studied in patients with various myotonic disorders. A decrementing response was common but not invariable finding, and was unrelated to the severity or diagnosis. The decrement either continued throughout the period of stimulation or "leveled off", sometimes being followed by an increment. If it occurred at low rates of stimulation, a greater decrement occurred at higher rates, usually after a shorter latent period. It was not related consistently to the presence of weakness, but in patients with myotonia congenita it was more conspicuous and elicited by lower rates of stimulation when transient weakness was a feature of the history.

Adolescent↗
PubMedDate not supplied

Recessive congenital myotonia and pregnancy.

There is a group of genetic disorders of muscle associated with myotonia. Congenital myotonia, usually a benign disorder and myotonic dystrophy, potentially a serious disorder, belong to this group. Uterine recordings during labor in patients with congenital myotonia have not been previously reported. These records have been abnormal in patients with myotonic dystrophy which has been associated with serious obstetric complications. A case of congenital myotonia in pregnancy is reported. The record of uterine contractions was normal. Although the patient delivered a stillborn male, the etiology of the intrauterine fetal demise is obscure.

Adolescent↗
PubMed1975

[Heterochronia of nerve fibers in man. Diagnostic value: initial results].

A classical physiological observation not usually apparent with methods used for detecting nerve potential in man, heterochronia of the nerve fibres is often found in extraordinary circumstances with considerably higher than normal frequence : mainly in muscular disorders, in particular myotonic dystrophy ; more incidentally in disorders of muscle tone. The authors draw attention to certain sources of error which could lead to wrong diagnosis of heterochronia and emphasize that these are only the initial results of research which needs to be pursued further.

Electric Stimulation↗
PubMed1979

Electrophysiological studies in two patients with dystrophia myotonica and atrioventricular conduction block.

Two patients with dystrophia myotonica showed high-grade atrio-ventricular block. Both underwent electrophysiological studies which revealed sinus and A-V nodal disease with normal intraventricular conduction in 1 case and His-Purkinje conduction disease in the other. Dystrophia myotonica may, therfore, involve all parts of the cardiac conduction system and may affect the generation of cardiac impulses. Pacemaker implantation may be necessary especially if drugs such as procainamide, which in addition to controlling myotonic symptoms may aggravate conduction disorders, are to be used.

Electrocardiography↗
PubMed2023

Dynamics and variability of transcriptomic dysregulation in congenital myotonic dystrophy during pediatric development.

Myotonic dystrophy type 1 (DM1) is a multi-systemic disorder caused by expansion of CTG microsatellite repeats within DMPK. The most severe form, congenital myotonic dystrophy (CDM), has symptom onset at birth due to large intergenerational repeat expansions. Despite a common mutation, CDM individuals present with a distinct clinical phenotype and absence of common DM1 symptoms. Given the clinical divergence, it is unknown if the hallmark of DM1 pathology, dysregulation of alternative splicing (AS) due to sequestration of MBNL proteins within toxic CUG repeat RNAs, contributes to disease throughout pediatric development. To evaluate global transcriptomic dysregulation, RNA-seq was performed on 36 CDM skeletal muscle biopsies ages 2 weeks to 16 years, including two longitudinal samples. Fifty DM1 and adult/pediatric controls were also sequenced as comparative groups. Despite a large CTG expansion and shared age of onset, CDM individuals presented with a heterogenous, MBNL-dependent mis-splicing signature. Estimation of intracellular MBNL concentrations from splicing responses of select events correlated with total spliceopathy and revealed a distinct, triphasic pattern of AS dysregulation across pediatric development. CDM infants (< 2 years) possess severe mis-splicing that significantly improves in early childhood (2-8 years) independent of sex or CTG repeat load. Adolescent individuals (8-16 years) stratified into two populations with a full range of global splicing dysregulation. DMPK expression changes correlated with alterations in splicing severity during development. This study reveals the complex dynamics of the CDM muscle transcriptome and provides insights into new therapeutic strategies, timing of therapeutic intervention, and biomarker development.

Child, Preschool↗
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↗
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↗