9,348 results match your criteria Congenital Myopathies

An Integrative Analysis of DNA Methylation Pattern in Myotonic Dystrophy Type 1 Samples Reveals a Distinct DNA Methylation Profile between Tissues and a Novel Muscle-Associated Epigenetic Dysregulation.

Biomedicines 2022 Jun 10;10(6). Epub 2022 Jun 10.

Neuromuscular and Neuropediatric Research Group, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Campus Can Ruti, Universitat Autònoma de Barcelona, 08916 Badalona, Spain.

Myotonic dystrophy type 1 (DM1) is a progressive, non-treatable, multi-systemic disorder. To investigate the contribution of epigenetics to the complexity of DM1, we compared DNA methylation profiles of four annotated CpG islands (CpGis) in the locus and neighbouring genes, in distinct DM1 tissues and derived cells, representing six DM1 subtypes, by bisulphite sequencing. In blood, we found no differences in CpGi 74, 43 and 36 in DNA methylation profile. Read More

View Article and Full-Text PDF

Metreleptin Treatment in a Boy with Congenital Generalized Lipodystrophy due to Homozygous c.465_468delGACT (p.T156Rfs*8) Mutation in the Gene; The First-year Results.

J Clin Res Pediatr Endocrinol 2022 Jun 23. Epub 2022 Jun 23.

Gazi Yasargil Training and Research Hospital, Pediatric Endocrinology, Diyarbakır, Turkey.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by an almost complete absence of body fat. In CGL, patients may have hyperphagia due to leptin deficiency. Recombinant human leptin (metreleptin) has been suggested as an effective treatment option. Read More

View Article and Full-Text PDF

Improvement of SLC29A3 spectrum disorder-related sensorineural hearing loss after initiation of IL-6 inhibitor.

BMJ Case Rep 2022 Jun 22;15(6). Epub 2022 Jun 22.

Pediatrics, Umm Al-Qura University College of Medicine, Makkah, Saudi Arabia

Tocilizumab is reported to reduce systemic inflammation in individuals with SLC29A3 spectrum disorder, but its effect on hearing loss has not been described. The authors present a boy toddler with a history of prematurity, dysphagia, hypersplenism, hyperpigmentation, short height and hearing loss who was referred to the immunology clinic. He initially presented shortly after birth with abnormal hearing screens followed by positive urine test for cytomegalovirus. Read More

View Article and Full-Text PDF

The most severe form of LMNA-associated congenital muscular dystrophy.

Brain Dev 2022 Jun 18. Epub 2022 Jun 18.

Division of Neurology, National Center for Child Health and Development (NCCHD), 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan; Department of Pediatrics, Shimada Ryoiku Medical Center for Challenged Children, 1-31-1 Nakazawa, Tama City, Tokyo 206-0036, Japan.

Alterations in the LMNA gene cause a wide spectrum of diseases collectively called laminopathies. LMNA-associated congenital muscular dystrophy is a form of laminopathy, which usually causes infantile onset of muscle weakness, predominantly in the cervical-axial muscles, and motor developmental retardation. Cardiac symptoms during the first decade of life are rare. Read More

View Article and Full-Text PDF

Genotype-phenotype spectrum and correlations in Xia-Gibbs syndrome: Report of five novel cases and literature review.

Birth Defects Res 2022 Jun 18. Epub 2022 Jun 18.

Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Background: Xia-Gibbs syndrome (XGS) is a rare neurodevelopmental disorder caused by pathogenic variants in the AT-hook DNA-binding motif-containing 1 gene (AHDC1), encoding a protein with a crucial role in transcription and epigenetic regulation, axonogenesis, brain function, and neurodevelopment. AHDC1 variants possibly act through a dominant-negative mechanism and may interfere with DNA repair processes, leading to genome instability and impaired DNA translesion repair. Variants affecting residues closer to the N-terminal are thought to determine a milder phenotype with better cognitive performances. Read More

View Article and Full-Text PDF

Coexistence of Megaconial Congenital Muscular Dystrophy and Cystinuria: Mimicking Hypotonia-Cystinuria Syndrome.

Mol Syndromol 2022 May 3;13(3):240-245. Epub 2022 Feb 3.

Department of Pediatric Metabolism, Faculty of Medicine, Ankara University, Ankara, Turkey.

Introduction: Hypotonia-cystinuria syndrome is a contiguous gene deletion syndrome that is characterized by hypotonia, developmental delay, and cystinuria type A. We present a male patient who was admitted to our center with clinical findings of hypotonia-cystinuria syndrome and diagnosed with megaconial congenital muscular dystrophy and cystinuria.

Case Presentation: A 16-month-old male patient was admitted with complaints of restlessness and body laxity. Read More

View Article and Full-Text PDF

Centronuclear Myopathy Caused by Defective Membrane Remodelling of Dynamin 2 and BIN1 Variants.

Int J Mol Sci 2022 Jun 3;23(11). Epub 2022 Jun 3.

Department of Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Kita-ku, Okayama 700-8558, Japan.

Centronuclear myopathy (CNM) is a congenital myopathy characterised by centralised nuclei in skeletal myofibers. T-tubules, sarcolemmal invaginations required for excitation-contraction coupling, are disorganised in the skeletal muscles of CNM patients. Previous studies showed that various endocytic proteins are involved in T-tubule biogenesis and their dysfunction is tightly associated with CNM pathogenesis. Read More

View Article and Full-Text PDF

Primary cilia in satellite cells are the mechanical sensors for muscle hypertrophy.

Proc Natl Acad Sci U S A 2022 Jun 7;119(24):e2103615119. Epub 2022 Jun 7.

Division of Geriatric Medicine & Gerontology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905.

Skeletal muscle atrophy is commonly associated with aging, immobilization, muscle unloading, and congenital myopathies. Generation of mature muscle cells from skeletal muscle satellite cells (SCs) is pivotal in repairing muscle tissue. Exercise therapy promotes muscle hypertrophy and strength. Read More

View Article and Full-Text PDF

A review of major causative genes in congenital myopathies.

J Hum Genet 2022 Jun 7. Epub 2022 Jun 7.

Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.

In this review, we focus on congenital myopathies, which are a genetically heterogeneous group of hereditary muscle diseases with slow or minimal progression. They are mainly defined and classified according to pathological features, with the major subtypes being core myopathy (central core disease), nemaline myopathy, myotubular/centronuclear myopathy, and congenital fiber-type disproportion myopathy. Recent advances in molecular genetics, especially next-generation sequencing technology, have rapidly increased the number of known causative genes for congenital myopathies; however, most of the diseases related to the novel causative genes are extremely rare. Read More

View Article and Full-Text PDF

Anesthesia of a patient with congenital cataract, facial dysmorphism, and neuropathy syndrome for posterior scoliosis: A case report.

World J Clin Cases 2022 May;10(13):4207-4213

Department of Pediatric Anesthesiology and Intensive Care Medicine, University Hospital Brno, Medical Faculty of Masaryk University, Brno 62500, Czech Republic.

Background: Congenital cataract, facial dysmorphism, and neuropathy (CCFDN) syndrome is an extremely rare multiorgan disorder. Characteristics include congenital cataracts, facial deformation, extremity deformities, and demyelinating neuropathy. CCFDN syndrome is associated with increased risk during anesthesia including rhabdomyolysis or epileptic seizures. Read More

View Article and Full-Text PDF

Screening and prevalence of cardiac abnormalities on electro- and echocardiography in a large cohort of patients with mitochondrial disease.

Mol Genet Metab 2022 Jul 28;136(3):219-225. Epub 2022 May 28.

Department of Neurology, Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Mitochondrial Medicine (RCMM), Radboudumc, Nijmegen, the Netherlands. Electronic address:

Background: In patients with primary mitochondrial disease (MD), screening with electrocardiogram (ECG) and transthoracic echocardiography (TTE) is warranted according to current guidelines as structural cardiac abnormalities are frequent. This study aims to evaluate the cardiac phenotype of a large Dutch cohort of patients with MD and investigates whether ECG alone is sufficient for predicting structural cardiac abnormalities on TTE.

Methods: In this retrospective cohort study, genetically confirmed MD patients >18 years old with an available ECG and TTE were included. Read More

View Article and Full-Text PDF

Orphan Drug Use in Patients With Rare Diseases: A Population-Based Cohort Study.

Front Pharmacol 2022 16;13:869842. Epub 2022 May 16.

Unit of Epidemiology of Rare Diseases and Congenital Anomalies, Institute of Clinical Physiology, National Research Council, Pisa, Italy.

Orphan drugs are used for the diagnosis, prevention and treatment of rare diseases that, in the European Union, are defined as disorders affecting no more than 5 persons in 10,000. So far, a total of around 800 orphan medicinal products have been approved by the European Medicines Agency, however the utilization profile of orphan drugs has yet to be explored. This study aimed at assessing the utilization profile of orphan drugs authorized for marketing by the Italian Medicines Agency using population-based data. Read More

View Article and Full-Text PDF

Impaired activity of the fusogenic micropeptide Myomixer causes myopathy resembling Carey-Fineman-Ziter syndrome.

J Clin Invest 2022 Jun;132(11)

Department of Molecular Biology and Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Skeletal muscle fibers contain hundreds of nuclei, which increase the overall transcriptional activity of the tissue and perform specialized functions. Multinucleation occurs through myoblast fusion, mediated by the muscle fusogens Myomaker (MYMK) and Myomixer (MYMX). We describe a human pedigree harboring a recessive truncating variant of the MYMX gene that eliminates an evolutionarily conserved extracellular hydrophobic domain of MYMX, thereby impairing fusogenic activity. Read More

View Article and Full-Text PDF

Rapid Molecular Diagnosis of Genetically Inherited Neuromuscular Disorders Using Next-Generation Sequencing Technologies.

J Clin Med 2022 May 12;11(10). Epub 2022 May 12.

Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain.

Neuromuscular diseases are genetically highly heterogeneous, and differential diagnosis can be challenging. Over a 3-year period, we prospectively analyzed 268 pediatric and adult patients with a suspected diagnosis of inherited neuromuscular disorder (INMD) using comprehensive gene-panel analysis and next-generation sequencing. The rate of diagnosis increased exponentially with the addition of genes to successive versions of the INMD panel, from 31% for the first iteration (278 genes) to 40% for the last (324 genes). Read More

View Article and Full-Text PDF

New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming.

J Exp Clin Cancer Res 2022 May 26;41(1):183. Epub 2022 May 26.

CIBERehd, Madrid, Spain.

Background: Cholangiocarcinoma (CCA) is still a deadly tumour. Histological and molecular aspects of thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats mimic those of human iCCA. Carcinogenic changes and therapeutic vulnerabilities in CCA may be captured by molecular investigations in bile, where we performed bile proteomic and metabolomic analyses that help discovery yet unknown pathways relevant to human iCCA. Read More

View Article and Full-Text PDF

Spinal muscular atrophy with respiratory distress type 1 (SMARD1): a rare cause of hypotonia, diaphragmatic weakness, and respiratory failure in infants.

Turk J Pediatr 2022 ;64(2):364-374

Department of Pediatric Neurology, University of Health Sciences, Dr. Behçet Uz Children's Education and Research Hospital, İzmir.

Background: Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a very rare autosomal recessive disorder caused by mutations in the immunoglobulin μ-binding protein-2 (IGHMBP2) gene on chromosome 11q13.2-q13.4. Read More

View Article and Full-Text PDF

Recognizable pattern of arthrogryposis and congenital myopathy caused by the recurrent TTN metatranscript-only c.39974-11T>G splice variant.

Neuropediatrics 2022 May 23. Epub 2022 May 23.

Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital, Heinrich-Heine-University, Düsseldorf, Germany., Düsseldorf, Germany.

Introduction: Arthrogryposis is characterized by the presence of multiple contractures at birth and can be caused by pathogenic variants in TTN (Titin). Exons and variants that are not expressed in one of the three major isoforms of titin are referred to as "metatranscript-only" and have been considered to be only expressed during fetal development. Recently, the metatranscript-only variant (c. Read More

View Article and Full-Text PDF

Guidance on medical physics expert support for nuclear medicine.

Br J Radiol 2022 Jul 25;95(1135):20211393. Epub 2022 May 25.

Nuclear Medicine, NHS Grampian, Aberdeen, Representing IPEM, United Kingdom.

The Ionising Radiation (Medical Exposure) Regulations require employers to appoint suitable medical physics experts (MPE) for nuclear medicine services, and they also define the areas where MPEs are required to provide advice and specify matters that they must contribute towards. Applications for employer licences under IR(ME)R require employers to specify the level of MPE support available and if this is provided by onsite MPEs or remotely. Assessment of these applications by the Administration of Radioactive Substances Advisory Committee (ARSAC) has highlighted variability in the levels of MPE support being provided for similar services across the UK. Read More

View Article and Full-Text PDF

[A novel splicing acceptor variant of the FBN2 gene contributes to a case of congenital contractural arachnodactyly].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 May;39(5):522-525

Department of Medical Genetics, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041,China.

Objective: To identify the pathogenic variants from a patient with suspected congenital contractural arachnodactyly, and to explore the possible molecular genetic pathogenesis, so as to provide evidence for clinical diagnosis.

Methods: Whole exome sequencing was performed for the patient. The splicing site variation of candidate pathogenic genes was verified by Sanger sequencing, and the new transcript sequence was determined by RT-PCR and TA-cloning sequencing. Read More

View Article and Full-Text PDF

Pulmonary lymphangiectasia in myotubular myopathy: a novel unrecognized association?

Neuromuscul Disord 2022 Jun 2;32(6):512-515. Epub 2022 May 2.

Division of Neonatology, Department of Pediatrics, McGill University Health Centre, Montreal, Quebec, Canada.

Chylothorax has been reported in rare cases of X-linked myotubular myopathy, but the pathophysiology of this association is not fully understood. We report a case of a neonate presenting prenatally with hydrops and chylothorax. The patient died at 17 days of life due to respiratory failure secondary to severe pulmonary hypertension. Read More

View Article and Full-Text PDF

A pathogenic mechanism associated with myopathies and structural birth defects involves TPM2-directed myogenesis.

JCI Insight 2022 Jun 22;7(12). Epub 2022 Jun 22.

Department of Developmental Biology, Washington University in St. Louis, St. Louis, Missouri, USA.

Nemaline myopathy (NM) is the most common congenital myopathy, characterized by extreme weakness of the respiratory, limb, and facial muscles. Pathogenic variants in Tropomyosin 2 (TPM2), which encodes a skeletal muscle-specific actin binding protein essential for sarcomere function, cause a spectrum of musculoskeletal disorders that include NM as well as cap myopathy, congenital fiber type disproportion, and distal arthrogryposis (DA). The in vivo pathomechanisms underlying TPM2-related disorders are unknown, so we expressed a series of dominant, pathogenic TPM2 variants in Drosophila embryos and found 4 variants significantly affected muscle development and muscle function. Read More

View Article and Full-Text PDF

A custom ddPCR method for the detection of copy number variations in the nebulin triplicate region.

PLoS One 2022 16;17(5):e0267793. Epub 2022 May 16.

Folkhälsan Research Center, Helsinki, Finland.

The human genome contains repetitive regions, such as segmental duplications, known to be prone to copy number variation. Segmental duplications are highly identical and homologous sequences, posing a specific challenge for most mutation detection methods. The giant nebulin gene is expressed in skeletal muscle. Read More

View Article and Full-Text PDF

Dilated-Left Ventricular Non-Compaction Cardiomyopathy in a Pediatric Case with Compound Heterozygous Variants.

Int J Mol Sci 2022 May 6;23(9). Epub 2022 May 6.

Aix Marseille University, INSERM, Marseille Medical Genetics, U1251 Marseille, France.

Left Ventricular Non-Compaction (LVNC) is defined by the triad prominent myocardial trabecular meshwork, thin compacted layer, and deep intertrabecular recesses. LVNC associated with dilation is characterized by the coexistence of left ventricular dilation and systolic dysfunction. Pediatric cases with dilated-LVNC have worse outcomes than those with isolated dilated cardiomyopathy and adult patients. Read More

View Article and Full-Text PDF

Electron microscopy in the diagnosis of skeletal muscle disorders: Its utility and limitations.

Indian J Pathol Microbiol 2022 May;65(Supplement):S291-S299

Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India.

Electron microscopy (EM) has a substantial role in the diagnosis of skeletal muscle disorders. The ultrastructural changes can be observed in muscle fibers and other components of the muscle tissue. EM serves as a confirmatory tool where the diagnosis is already established by enzyme histochemistry staining. Read More

View Article and Full-Text PDF

Congenital myopathies: The current status.

Indian J Pathol Microbiol 2022 May;65(Supplement):S271-S276

Charite - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Chariteplatz 1, Berlin, Germany.

Within the history of neuromuscular diseases (NMD), congenital myopathies (CM) represent a relatively new category introduced in the mid-nineteen hundreds upon advent and subsequent application of enzyme histochemistry and electron microscopy by establishing the three major CM, central core disease, nemaline myopathy, and centronuclear myopathy which later pluralized each when the molecular era began at the end of last century. Quickly, during the following 5 decades, many new CM entities were described, based on muscle biopsies and their CM-characteristic myopathology, the former a prerequisite to recognizing an individual CM, the latter of the nosological hallmark of the individual CM. When the molecular era ushered in immunohistochemistry the spectrum and nosography of CM altered in that some CM became allelic to other cohorts of NMD, e. Read More

View Article and Full-Text PDF

Genetics and muscle pathology in the diagnosis of muscular dystrophies: An update.

Indian J Pathol Microbiol 2022 May;65(Supplement):S259-S270

Department of Medical Genetics, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India.

Muscular dystrophies are a clinically and genetically heterogeneous group of disorders involving the skeletal muscles. They have a progressive clinical course and are characterized by muscle fiber degeneration. Congenital muscular dystrophies (CMD) include dystroglycanopathies, merosin-deficient CMD, collagen VI-deficient CMD, SELENON-related rigid spine muscular dystrophy, and LMNA-related CMD. Read More

View Article and Full-Text PDF

Basic requirements to establish a neuromuscular laboratory.

Indian J Pathol Microbiol 2022 May;65(Supplement):S233-S240

Department of Neuropathology, NIMHANS, Bangalore, Karnataka, India.

Histopathological analysis of muscle biopsy is a prerequisite in the evaluation of neuromuscular disorders, particularly inflammatory myopathies, metabolic myopathies, congenital myopathies, muscular dystrophies and differentiating myopathies and neurogenic disorders with overlapping clinically features. It not only provides useful information that helps in the diagnosis but also treatment and management. Fundamental skills and basic knowledge regarding handling, processing and analyzing a muscle biopsy are required in any specialized or a general pathology lab supporting neuromuscular clinical services. Read More

View Article and Full-Text PDF

Coexisting sporadic late onset nemaline myopathy and AL amyloid myopathy - incidental or related?

Neuromuscul Disord 2022 Jun 26;32(6):533-538. Epub 2022 Mar 26.

Department of Neurology, Oregon Health & Science University, Portland, OR, USA. Electronic address:

Sporadic late onset nemaline myopathy (SLONM) and amyloid myopathy are frequently unrecognized acquired and treatable myopathies, which classically present with rapidly progressive and severe proximal muscle weakness. We report a case of SLONM and amyloid myopathy associated with IgM lambda monoclonal gammopathy in a 77-year-old Caucasian man. Creatine kinase (CK) was mildly elevated. Read More

View Article and Full-Text PDF

Congenital myopathies in adults: A diagnosis not to overlook.

Acta Neurol Scand 2022 May 12. Epub 2022 May 12.

Department of Neurology, Centro Hospitalar Universitário de São João, E.P.E., Porto, Portugal.

Background: Congenital myopathies (CM) were traditionally classified according to the muscle histopathological features, but in recent years, molecular diagnosis has become increasingly important. CM may present a wide phenotype variability, and while adult-onset CM have been increasingly recognized, substantial diagnostic delays are still reported.

Objectives: To describe a cohort of adult CM patients, including clinical, genetic, and histopathological features, and further characterize the subgroup of adult-diagnosed patients. Read More

View Article and Full-Text PDF

Congenital muscle dystrophies: Role of singleton whole exome sequencing in countries with limited resources.

Clin Neurol Neurosurg 2022 06 2;217:107271. Epub 2022 May 2.

University of Iowa Healthcare, USA. Electronic address:

Aim: Identify the genetic determinants of congenital muscle dystrophy (CMD) in Jordanian children.

Methods: This prospective study included patients suspected to have CMD. Singleton whole-exome sequencing (WES) was performed as the first-tier diagnostic test. Read More

View Article and Full-Text PDF