"Myotonic dystrophy"

Diagnosis and Management of Myotonic Dystrophy Type 1. This JAMA Insights discusses the signs and symptoms, diagnosis, and treatment of myotonic dystrophy type 1.

Myotonic Dystrophy and Stress Induced Cardiomyopathy: A Case Series. Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder with a broad spectrum of systemic manifestations, including cardiac abnormalities. Takotsubo cardiomyopathy, a form of stress-induced transient heart failure, is not typically associated with DM1, and its occurrence in this patient population remains poorly

The Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1. Myotonic dystrophy type 1 (DM1) is a multisystemic, CTG repeat expansion disorder characterized by a slow, progressive decline in skeletal muscle function. A biomarker correlating RNA mis-splicing, the core pathogenic disease mechanism, and muscle performance is crucial for assessing response to disease-modifying interventions. We evaluated the Myotonic Dystrophy Splice Index (SI), a composite RNA splicing biomarker incorporating 22 disease-specific events, as a potential biomarker of DM1 muscle weakness. Total RNA sequencing of tibialis anterior biopsies from 58 DM1 participants and 33 unaffected/disease controls was used to evaluate RNA splicing events across the disease spectrum. Targeted

MBNL overexpression rescues cardiac phenotypes in a myotonic dystrophy type 1 heart mouse model. Myotonic Dystrophy Type 1 (DM1) is an autosomal dominant disease caused by a CTG repeat expansion in the DMPK gene. The expanded CUG repeat RNA (CUGexp RNA) transcribed from the mutant allele sequesters the muscleblind-like (MBNL) family of RNA-binding proteins, causing their loss of function

Verapamil mitigates chloride and calcium bi-channelopathy in a myotonic dystrophy mouse model. Myotonic dystrophy type 1 (DM1) involves misregulated alternative splicing for specific genes. We used exon or nucleotide deletion to mimic altered splicing of genes central to muscle excitation-contraction coupling in mice. Mice with forced skipping of exon 29 in the CaV1.1 calcium channel combined

Combinatorial effects of ion channel mis-splicing as a cause of myopathy in myotonic dystrophy. Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder caused by an unstable expanded CTG repeat located in the 3'-UTR of the DM1 protein kinase (DMPK) gene. The pathogenic mechanism results in misregulated alternative splicing of hundreds of genes, creating the dilemma of establishing which

Neurobehavioral Phenotype of Children With Congenital Myotonic Dystrophy. To describe the neurobehavioral phenotype of congenital myotonic dystrophy. Congenital myotonic dystrophy (CDM) is the most severe form of myotonic dystrophy, characterized by symptom presentation at birth and later, cognitive impairment, autistic features, and disordered sleep. The neurobehavioral phenotype was assessed

Myotonic dystrophy type 1: palliative care guidelines. Palliative care for adults with neuromuscular conditions is an emerging field. Previous guidelines regarding myotonic dystrophy and palliative care have only mentioned end-of-life care and little else. The following guidelines have been written using national experts as a description of best practice as part of the Dystrophia Myotonica

Multi-level profiling unravels mitochondrial dysfunction in myotonic dystrophy type 2. Myotonic dystrophy type 2 (DM2) is an autosomal-dominant multisystemic disease with a core manifestation of proximal muscle weakness, muscle atrophy, myotonia, and myalgia. The disease-causing CCTG tetranucleotide expansion within the CNBP gene on chromosome 3 leads to an RNA-dominated spliceopathy, which is currently untreatable. Research exploring the pathophysiological mechanisms in myotonic dystrophy type 1 has resulted in new insights into disease mechanisms and identified mitochondrial dysfunction as a promising therapeutic target. It remains unclear whether similar mechanisms underlie DM2 and, if so, whether these might also serve as potential therapeutic targets. In this cross-sectional study, we

Parental diagnostic delay and developmental outcomes in congenital and childhood-onset myotonic dystrophy type 1. To investigate the timing of type 1 myotonic dystrophy (DM1) diagnosis in parents of affected children and describe children's perinatal characteristics and developmental outcomes. This was a descriptive case series of children with congenital myotonic dystrophy (CDM) and childhood -onset myotonic dystrophy (ChDM). Parental timing of DM1 diagnosis and the perinatal, motor, and cognitive outcomes of paediatric patients were recorded. A total of 139 children followed by 12 highly specialized tertiary care neuromuscular centres in Italy and one tertiary neuromuscular centre in the USA were included: 105 children with CDM and 34 children with ChDM (mean age 8 years 8 months and 12

Myotonic dystrophy type 1 testing, 2024 revision: A technical standard of the American College of Medical Genetics and Genomics (ACMG). Myotonic dystrophy type 1 (DM1) is a form of muscular dystrophy causing progressive muscle loss and weakness. Although clinical features can manifest at any age, it is the most common form of muscular dystrophy with onset in adulthood. DM1 is an autosomal dominant condition, resulting from an unstable CTG expansion in the 3'-untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. The age of onset and the severity of the phenotype are roughly correlated with the size of the CTG expansion. Multiple methodologies can be used to diagnose affected individuals with DM1, including polymerase chain reaction, Southern blot, and triplet repeat

Cancer Risk in Patients With Muscular Dystrophy and Myotonic Dystrophy: A Register-Based Cohort Study. Muscular dystrophies and myotonic disorders are genetic disorders characterized by progressive skeletal muscle degeneration and weakness. Epidemiologic studies have found an increased cancer risk in myotonic dystrophy, although the cancer risk spectrum is poorly characterized. In patients with muscular dystrophy, the cancer risk is uncertain. We aimed to determine the overall cancer risk and cancer risk spectrum in patients with muscular dystrophy and myotonic dystrophy using data from the Swedish National registers. We performed a matched cohort study in all patients with muscular dystrophy or myotonic dystrophy born in Sweden 1950-2017 and 50 matched comparisons by sex, year of birth

Myotonic dystrophy test ManualsLibraryEducationFoundation My CPDPMy Quick Links My RCPA Advanced SearchHomeEventsNews & MediaPathology CareersPathology UpdateAboutContact UsManuals RCPA Manual Pathology Tests M Myotonic dystrophy testMYOTONIC DYSTROPHY TESTSPECIMEN: 10-20 mL blood in EDTA tube.METHOD: PCR screen followed by Southern blot analysis to detect an expanded triplet repeat mutation in the myotonic dystrophy protein kinase gene (DMPK).APPLICATION: Used to detect the myotonic dystrophy type 1 (DM1) mutation in symptomatic or asymptomatic people.Prenatal diagnosis for myotonic dystrophy is available if the mother has been shown to have an abnormal gene.  Additional information about genetic tests may be available in RCPA Catalogue of Genetic Tests and Laboratories.INTERPRETATION: Myotonic

Suitability of the Respicheck questionnaire and Epworth sleepiness scale for therapy monitoring in myotonic dystrophy type 1. Myotonic dystrophy type 1 (DM1) is an autosomal dominant trinucleotide disorder that often leads to respiratory dysfunction resulting in hypoventilation symptoms, reduced quality of life and causing premature death if untreated. To early identify symptoms

Antisense oligonucleotide targeting DMPK in patients with myotonic dystrophy type 1: a multicentre, randomised, dose-escalation, placebo-controlled, phase 1/2a trial. Myotonic dystrophy type 1 results from an RNA gain-of-function mutation, in which DM1 protein kinase (DMPK) transcripts carrying expanded trinucleotide repeats exert deleterious effects. Antisense oligonucleotides (ASOs) provide a promising approach to treatment of myotonic dystrophy type 1 because they reduce toxic RNA levels. We aimed to investigate the safety of baliforsen (ISIS 598769), an ASO targeting DMPK mRNA. In this dose-escalation phase 1/2a trial, adults aged 20-55 years with myotonic dystrophy type 1 were enrolled at seven tertiary referral centres in the USA and randomly assigned via an interactive web or phone

Unexpected diagnosis of myotonic dystrophy type 2 repeat expansion by genome sequencing. Several neurological disorders, such as myotonic dystrophy are caused by expansions of short tandem repeats (STRs) which can be difficult to detect by molecular tools. Methodological advances have made repeat expansion (RE) detection with whole genome sequencing (WGS) feasible. We recruited a multi -generational family (family A) ascertained for genetic studies of autism spectrum disorder. WGS was performed on seven children from four nuclear families from family A and analyzed for REs of STRs known to cause neurological disorders. We detected an expansion of a heterozygous intronic CCTG STR in CNBP in two siblings. This STR causes myotonic dystrophy type 2 (DM2). The expansion did not segregate

Erythromycin for myotonic dystrophy type 1: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Myotonic dystrophy type 1 (DM1) is a devastating multisystemic disorder caused by a CTG repeat expansion in the gene, which subsequently triggers toxic RNA expression and dysregulated splicing. In a preclinical study, we demonstrated that erythromycin reduces the toxicity

Individual transcriptomic response to strength training for myotonic dystrophy type 1 patients. Myotonic dystrophy type 1 (DM1), the most common form of adult-onset muscular dystrophy, is caused by a CTG expansion resulting in significant transcriptomic dysregulation that leads to muscle weakness and wasting. While strength training is clinically beneficial in DM1, molecular effects had not been

Choroid plexus mis-splicing and altered cerebrospinal fluid composition in myotonic dystrophy type 1. Myotonic dystrophy type 1 is a dominantly inherited multisystemic disease caused by CTG tandem repeat expansions in the DMPK 3' untranslated region. These expanded repeats are transcribed and produce toxic CUG RNAs that sequester and inhibit activities of the MBNL family of developmental RNA processing factors. Although myotonic dystrophy is classified as a muscular dystrophy, the brain is also severely affected by an unusual cohort of symptoms, including hypersomnia, executive dysfunction, as well as early onsets of tau/MAPT pathology and cerebral atrophy. To address the molecular and cellular events that lead to these pathological outcomes, we recently generated a mouse Dmpk CTG expansion

Comprehensive transcriptome-wide analysis of spliceopathy correction of myotonic dystrophy using CRISPR-Cas9 in iPSCs-derived cardiomyocytes. CTG repeat expansion (CTG) is associated with aberrant alternate splicing that contributes to cardiac dysfunction in myotonic dystrophy type 1 (DM1). Excision of this CTG repeat using CRISPR-Cas resulted in the disappearance of punctate ribonuclear foci