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Channels (Austin, Tex.) Dec 2024Myotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain...
Myotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain between dominant-type Thomsen (TMC) and recessive-type Becker (BMC). The clinical data and auxiliary examinations of MC patients in our clinic were retrospectively collected. Electromyography was performed in 11 patients and available family members. Whole exome sequencing was conducted in all patients. The clinical and laboratory data of Chinese MC patients reported from June 2004 to December 2022 were reviewed. A total of 11 MC patients were included in the study, with a mean onset age of 12.64 ± 2.73 years. The main symptom was muscle stiffness of limbs. Warm-up phenomenon and percussion myotonia were found in all patients. Electromyogram revealed significant myotonic charges in all patients and two asymptomatic carriers, while muscle MRI and biopsy showed normal or nonspecific changes. Fourteen genetic variants including 6 novel variants were found in CLCN1. Ninety-eight Chinese patients were re-analyzed and re-summarized in this study. There were no significant differences in the demographic data, clinical characteristics, and laboratory findings between 52 TMC and 46 BMC patients. Among the 145 variants in CLCN1, some variants, including the most common variant c.892 G>A, could cause TMC in some families and BMC in others. This study expanded the clinical and genetic spectrum of Chinese patients with MC. It was difficult to distinguish between TMC and BMC only based on the clinical, laboratory, and genetic characteristics.
Topics: Humans; Myotonia Congenita; Male; Female; Chloride Channels; Child; Adolescent; Asian People; Adult; Young Adult; Electromyography; Retrospective Studies; China; Mutation; East Asian People
PubMed: 38720415
DOI: 10.1080/19336950.2024.2349823 -
American Journal of Medical Genetics.... May 2024Myotonic dystrophy type 1 is an autosomal dominant condition due to a CTG repeat expansion in the myotonic dystrophy protein kinase (DMPK) gene. This multisystem...
Myotonic dystrophy type 1 is an autosomal dominant condition due to a CTG repeat expansion in the myotonic dystrophy protein kinase (DMPK) gene. This multisystem disorder affects multiple organ systems. Hypogonadism in males affected by myotonic dystrophy is commonly reported; however, the effect on female hypogonadism remains controversial. A 19-year-old female was referred to our genetics clinic due to primary amenorrhea without any family history of similar symptoms. Initial genetics evaluation identified a variant of uncertain significance in IGSF10, c.2210T>C (p.Phe737Ser). Follow-up genetic evaluation via whole genome sequencing identified at least 100 CTG repeats in the DMPK gene, thus resulting in the diagnosis of myotonic dystrophy type 1. The patient remains otherwise asymptomatic from myotonic dystrophy. This is the first report that demonstrates primary amenorrhea as a possible presenting feature of myotonic dystrophy type 1, thus providing evidence supporting female hypogonadism in myotonic dystrophy type 1.
PubMed: 38709060
DOI: 10.1002/ajmg.a.63650 -
Stem Cell Research Jun 2024Congenital myotonic dystrophy (CDM) is a genetic disease caused by an abnormally long CTG repeat expansion in the DMPK gene, which generally increases in size following...
Congenital myotonic dystrophy (CDM) is a genetic disease caused by an abnormally long CTG repeat expansion in the DMPK gene, which generally increases in size following intergenerational transmission. CDM is the rarest and most severe form of myotonic dystrophy type 1, yet an important number of patient-derived cells are needed to study this heterogeneous disease. Therefore, we have reprogrammed lymphoblastoid cells derived from a 3-year-old male with CDM into induced pluripotent stem cells (iPSCs; CBRCULi015-A) featuring 1800 CTG repeats and characterized their pluripotent state. This cell line constitutes an important resource to study CDM and potential treatments in vitro.
Topics: Humans; Myotonic Dystrophy; Induced Pluripotent Stem Cells; Male; Child, Preschool; Cell Line; Cell Differentiation; Myotonin-Protein Kinase
PubMed: 38704930
DOI: 10.1016/j.scr.2024.103430 -
Primary Care Jun 2024Muscle weakness and pain can be seen in orthopedic, rheumatologic, cardiac, and musculoskeletal conditions in addition to neurologic disorders. Myopathy, which describes... (Review)
Review
Muscle weakness and pain can be seen in orthopedic, rheumatologic, cardiac, and musculoskeletal conditions in addition to neurologic disorders. Myopathy, which describes a heterogenous group of hereditary and acquired disorders that affect muscle channels, structure, and metabolism, is one possible cause. This review focuses on essential information to support primary care providers as they assess patients with muscle weakness and pain for myopathy. As with most neurologic disorders, a thorough clinical history and physical examination are essential first steps. These findings will then guide diagnostic testing and facilitate appropriate management or referral for further neuromuscular care.
Topics: Humans; Muscle Weakness; Muscular Diseases; Physical Examination; Primary Health Care; Myalgia; Diagnosis, Differential; Medical History Taking
PubMed: 38692777
DOI: 10.1016/j.pop.2024.02.005 -
BMC Psychology Apr 2024The COVID-19 pandemic substantially affected the lives of persons with inherited neuromuscular disorders (INMD), causing disruption in clinical and support services....
BACKGROUND
The COVID-19 pandemic substantially affected the lives of persons with inherited neuromuscular disorders (INMD), causing disruption in clinical and support services. While several studies have investigated mental health, distress and psychosocial resources in the general population during the pandemic, little is known about the experience of persons with INMD.
METHODS
This study was aimed to fill this gap by jointly investigating both psychopathological symptoms and psychosocial resources - specifically, resilience and perceived social support - among persons with INMD during the pandemic, taking into account demographic and clinical factors. Between April and December 2020, 59 participants with INMD (aged 15-59, 71.2% M) completed a questionnaire collecting demographic and clinical data, the Multidimensional Scale of Perceived Social Support, the Resilience Scale for Adults, and the Achenbach System of Empirically Based Assessment.
RESULTS
Overall, participants showed good levels of resilience and perceived social support. A minority of participants reported clinically relevant psychopathological symptoms, 28.81% for anxiety and depression. Most psychopathological symptoms were negatively correlated with resilience (-0.347 < r < - .420), but not significantly associated with social support. Consistent with previous studies, regression analyses highlighted that participants with Duchenne muscular dystrophy were more prone to report anxious and depressive symptoms (B = 1.748, p = .028, OR = 5.744), and participants with myotonic dystrophy, attention problems (B = 2.339, p = .006, OR = 10.376). Resilience emerged as a potential predictor of lower anxious-depressive symptoms (B=-1.264, p = .012, OR = 0.283).
CONCLUSIONS
The findings suggest the importance to investigate psychosocial resources in addition to psychopathology among persons with INMD, and to design interventions supporting resilience as a protective factor for mental health promotion.
Topics: Humans; COVID-19; Adult; Male; Female; Middle Aged; Resilience, Psychological; Neuromuscular Diseases; Social Support; Adolescent; Young Adult; Anxiety; Depression; Surveys and Questionnaires; SARS-CoV-2
PubMed: 38685111
DOI: 10.1186/s40359-024-01742-5 -
Revista de Neurologia May 2024Genetic myopathies constitute a collection of rare diseases that significantly impact patient functionality and quality of life. Early diagnosis of genetic myopathies... (Observational Study)
Observational Study
INTRODUCTION
Genetic myopathies constitute a collection of rare diseases that significantly impact patient functionality and quality of life. Early diagnosis of genetic myopathies can prevent future complications and provide families with genetic counselling. Despite the substantial impact of genetic myopathies on the adult population, the global epidemiology of these disorders is inadequately addressed in the literature.
AIMS
To enhance understanding of both the epidemiology and genetics of these disorders within the province of Alicante, situated in southeastern Spain.
MATERIAL AND METHODS
Between 2020 and 2022, a prospective observational study was conducted at the Alicante Health Area-General Hospital, enrolling patients aged 16 years or older with suspected genetic myopathies. Sociodemographic, clinical, and genetic data were collected. The reference date for prevalence calculation was established as December 31, 2022. Official demographic data of the health area were used to set the population at risk.
RESULTS
In total, 83 patients were identified with confirmed genetically related myopathy, resulting in an overall prevalence of 29.59 cases per 100,000 inhabitants. The diagnostic yield for molecular genetic testing was found to be 69.16%. The most prevalent genetic myopathies identified included myotonic dystrophy (27.5%), dystrophinopathies (15.7%), and facioscapulohumeral dystrophy (15.7%).
CONCLUSION
The prevalence of GMs can vary considerably depending on the geographical region and the studied population. The analysis of diagnostic yield suggests that genetic studies should be considered useful in the diagnosis of genetic myopathies.
Topics: Humans; Spain; Male; Female; Adult; Prospective Studies; Middle Aged; Prevalence; Muscular Diseases; Aged; Young Adult; Adolescent
PubMed: 38682761
DOI: 10.33588/rn.7809.2024071 -
Nigerian Journal of Clinical Practice Apr 2024Myotonic dystrophy (DM) is an autosomal dominant genetic disorder characterized by progressively worsening loss of muscle mass and weakness. Anesthesiologists face...
Myotonic dystrophy (DM) is an autosomal dominant genetic disorder characterized by progressively worsening loss of muscle mass and weakness. Anesthesiologists face challenges in managing these patients due to risks such as prolonged intubation and delayed recovery associated with anesthesia in such conditions. We report a case of a 40-year-old male patient undergoing open total gastrectomy under general anesthesia. After the surgery, we administered sugammadex to reverse neuromuscular blockade and confirmed the patient's spontaneous breathing. We then proceeded to extubate the patient. However, the patient experienced complications such as apnea, desaturation, and mental changes. The patient was re-intubated and transferred to the intensive care unit for ventilator support. He was diagnosed with DM by genetic test later. Poor preoperative assessment or undiagnosed DM in surgical patients can lead to severe complications. Thus, it is important to carefully check preoperative laboratory results, patient history, and physical findings.
Topics: Humans; Myotonic Dystrophy; Male; Adult; Anesthesia, General; Gastrectomy; Sugammadex; Neuromuscular Blockade
PubMed: 38679780
DOI: 10.4103/njcp.njcp_553_23 -
Archives of Cardiovascular Diseases 2024In France, mexiletine - a class I antiarrhythmic drug - can be prescribed for the symptomatic treatment of myotonia of the skeletal muscles in adult patients with... (Review)
Review
In France, mexiletine - a class I antiarrhythmic drug - can be prescribed for the symptomatic treatment of myotonia of the skeletal muscles in adult patients with myotonic dystrophy under a compassionate use programme. Mexiletine is used according to its summary of product characteristics, which describes its use for myotonia treatment in adult patients with non-dystrophic myotonia, a different neuromuscular condition without cardiac involvement. A cardiac assessment is required prior to initiation and throughout treatment due to potential proarrhythmic effects. The presence of conduction system disease, the most common cardiac manifestation of myotonic dystrophy, mandates repeated cardiac evaluations in patients with this condition, and becomes even more important when they are given mexiletine. A group of experts, including three neurologists and five cardiologists from French neuromuscular reference centres, were involved in a task force to develop a treatment algorithm to guide mexiletine use in myotonic dystrophy. The recommendations are based on data from a literature review of the safety of mexiletine-treated patients with myotonic dystrophy, the compassionate use protocol for mexiletine and the personal clinical experience of the experts. The main conclusion of the expert group is that, although existing safety data in mexiletine-treated patients with myotonic dystrophy are reassuring, cardiac assessments should be reinforced in such patients compared with mexiletine-treated patients with non-dystrophic myotonia. This expert opinion to guide mexiletine treatment in patients with myotonic dystrophy should help to reduce the risk of severe adverse events and facilitate interactions between specialists involved in the routine care of patients with myotonic dystrophy.
Topics: Adult; Humans; Algorithms; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Decision-Making; Compassionate Use Trials; Consensus; France; Mexiletine; Myotonic Dystrophy; Risk Assessment; Risk Factors; Treatment Outcome; Voltage-Gated Sodium Channel Blockers
PubMed: 38677940
DOI: 10.1016/j.acvd.2024.03.001 -
Tidsskrift For Den Norske Laegeforening... Apr 2024Myotonic dystrophy type 1 is an autosomal dominant, inherited multiorgan disorder that can affect people of all ages. It is the most prevalent inherited muscular disease... (Review)
Review
Myotonic dystrophy type 1 is an autosomal dominant, inherited multiorgan disorder that can affect people of all ages. It is the most prevalent inherited muscular disease in adults. Late diagnosis points to limited knowledge among the medical community that symptoms other than typical muscular symptoms can dominate. The condition often worsens with each generation and some families are severely affected. Significantly delayed diagnosis means a risk of more serious development of the disorder and inadequate symptomatic treatment. We hope that this clinical review article may lead to more rapid diagnosis and better follow-up of this patient group.
Topics: Myotonic Dystrophy; Humans; Delayed Diagnosis; Adult
PubMed: 38651711
DOI: 10.4045/tidsskr.23.0687 -
Biomedica : Revista Del Instituto... Mar 2024Introduction. During the development of the SARS-CoV-2 pandemic in Antioquia, we experienced epidemiological peaks related to the α, ɣ, β, ƛ, and δ variants. δ had...
Introduction. During the development of the SARS-CoV-2 pandemic in Antioquia, we experienced epidemiological peaks related to the α, ɣ, β, ƛ, and δ variants. δ had the highest incidence and prevalence. This lineage is of concern due to its clinical manifestations and epidemiological characteristics. A total of 253 δ sublineages have been reported in the PANGOLIN database. The sublineage identification through genomic analysis has made it possible to trace their evolution and propagation. Objective. To characterize the genetic diversity of the different SARS-CoV-2 δ sublineages in Antioquia and to describe its prevalence. Materials and methods. We collected sociodemographic information from 2,675 samples, and obtained 1,115 genomes from the GISAID database between July 12th, 2021, and January 18th, 2022. From the analyzed genomes, 515 were selected because of their high coverage values (>90%) to perform phylogenetic analysis and to infer allele frequencies of mutations of interest. Results. We characterized 24 sublineages. The most prevalent was AY.25. Mutations of interest as L452R, P681R, and P681H were identified in this sublineage, comprising a frequency close to 0.99. Conclusions. This study identified that the AY.25 sublineage has a transmission advantage compared to the other δ sublineages. This attribute may be related to the presence of the L452R and P681R mutations associated in other studies with higher evasion of the immune system and less efficacy of drugs against SARS-CoV-2.
Topics: Colombia; COVID-19; Humans; SARS-CoV-2; Phylogeny; Genome, Viral; Male; Female; Mutation; Adult; Middle Aged; Pandemics; Young Adult; Aged; Adolescent; Gene Frequency; Genetic Variation
PubMed: 38648352
DOI: 10.7705/biomedica.6862