scholarly journals Genetic Landscape of Congenital Myasthenic Syndromes From Turkey: Novel Mutations and Clinical Insights

2017 ◽  
Vol 32 (8) ◽  
pp. 759-765 ◽  
Author(s):  
Uluç Yiş ◽  
Kerstin Becker ◽  
Semra Hız Kurul ◽  
Gökhan Uyanik ◽  
Erhan Bayram ◽  
...  
Keyword(s):  
Cholinesterase Inhibitors ◽  
Neuromuscular Disorders ◽  
Genetic Diagnosis ◽  
Common Type ◽  
Child Neurology ◽  
Novel Mutations ◽  
Congenital Myasthenic Syndromes ◽  
Genetic Landscape ◽  
Prompt Diagnosis ◽  
Myasthenic Syndromes

Congenital myasthenic syndromes are clinically and genetically heterogeneous disorders of neuromuscular transmission. Most are treatable, but certain subtypes worsen with cholinesterase inhibitors. This underlines the importance of genetic diagnosis. Here, the authors report on cases with genetically proven congenital myasthenic syndromes from Turkey. The authors retrospectively reviewed their experience of all patients with congenital myasthenic syndromes, referred over a 5-year period (2011-2016) to the Child Neurology Department of Dokuz Eylül University, Izmir, Turkey. In addition, PubMed was searched for published cases of genetically proven congenital myasthenic syndromes originating from Turkey. In total, the authors identified 43 (8 new patients, 35 recently published patients) cases. Defects in the acetylcholine receptor (n = 15; 35%) were the most common type, followed by synaptic basal-lamina associated (n = 14; 33%) and presynaptic syndromes (n = 10; 23%). The authors had only 3 cases (7%) who had defects in endplate development. One patient had mutation GFPT1 gene (n = 1; 2%). Knowledge on congenital myasthenic syndromes and related genes in Turkey will lead to prompt diagnosis and treatment of these rare neuromuscular disorders.

scholarly journals Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 539
Author(s):  
Lidia Gonzalez-Quereda ◽  
Maria Jose Rodriguez ◽  
Jordi Diaz-Manera ◽  
Jorge Alonso-Perez ◽  
Eduard Gallardo ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Neuromuscular Disorders ◽  
Neuromuscular Disorder ◽  
Gene Panel ◽  
Muscular Dystrophies ◽  
Next Generation ◽  
Congenital Myasthenic Syndromes ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing ◽  
Myasthenic Syndromes

The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as TTN, NEB and RYR1. We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49.3%), involving 42 NMD-related genes. The most common causative genes, TTN and RYR1, accounted for almost 30% of cases. Thirty-two of the 207 patients (15.4%) carried variants of uncertain significance or had an unidentified second mutation to explain the genetic cause of the disease. In the remaining 73 patients (35.3%), no candidate variant was identified. In combination with patients’ clinical and myopathological data, the custom gene panel designed in our lab proved to be a powerful tool to diagnose patients with myopathies, muscular dystrophies and congenital myasthenic syndromes. Targeted NGS approaches enable a rapid and cost-effective analysis of NMD- related genes, offering reliable results in a short time and relegating invasive techniques to a second tier.

The Increasing Genetic and Phenotypical Diversity of Congenital Myasthenic Syndromes

2017 ◽  
Vol 48 (04) ◽  
pp. 294-308 ◽  
Author(s):  
Angela Abicht ◽  
Teresinha Evangelista ◽  
Sally Spendiff ◽  
Hanns Lochmüller ◽  
Grace McMacken
Keyword(s):  
Therapeutic Intervention ◽  
Genetic Diagnosis ◽  
Muscular Dystrophies ◽  
Diverse Group ◽  
Peripheral Neuropathies ◽  
Critical Importance ◽  
Congenital Myasthenic Syndromes ◽  
Pathologic Features ◽  
Myasthenic Syndromes

AbstractThe congenital myasthenic syndromes (CMS) are a diverse group of diseases, which result in an increasing range of phenotypes, but which are all due to inherited defects at the neuromuscular junction (NMJ). Although some patients remain genetically undiagnosed, our ability to identify the causative genes has shed new light on the role of previous uncharacterized proteins at the NMJ. Securing the genetic diagnosis can be challenging, but it is of critical importance to allow rational therapeutic intervention. In this review, we summarize the key clinical and pathologic features of the CMS subtypes, outline diagnostic clues, and challenges, and describe the recent advances that have highlighted the overlap between CMS and the muscular dystrophies and peripheral neuropathies.

Neuromuscular Junction Disorders

2015 ◽  
Author(s):  
Anthony A Amato ◽  
Mohammad Kian Salajegheh
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Motor Nerve ◽  
Neuromuscular Disorders ◽  
Synaptic Cleft ◽  
Organophosphate Poisoning ◽  
Electric Currents ◽  
Repetitive Nerve Stimulation ◽  
Congenital Myasthenic Syndromes ◽  
Myasthenic Syndromes

The three main components of the neuromuscular junction (NMJ) include the presynaptic region, the synaptic cleft, and the postsynaptic region. The NMJ acts as an interface between the motor nerve and muscle by converting the motor nerve electric currents into chemical signals and then back into electric currents in the muscle. This chapter reviews electrodiagnostic testing in NMJ disorders, including repetitive nerve stimulation and single-fiber electromyography. Myasthenia gravis, congenital myasthenic syndromes, Lambert-Eaton myasthenic syndrome, botulism, and organophosphate poisoning and other toxins are discussed, including epidemiology, etiology/genetics, pathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis. Tables include an overview of neuromuscular disorders, drugs with adverse effects on the NMJ, common immunomodulatory agents used for treatment of myasthenia gravis, congenital myasthenic syndromes, and toxins and venoms. Figures illustrate the NMJ structure and function, structure of the presynaptic and postsynaptic regions, electrodiagnostic studies in NMJ disorders, and dysfunction of the NMJ in acetylcholine receptor myasthenia gravis. This chapter contains 5 highly rendered figures, 5 tables, 65 references, and 5 MCQs.

Neuromuscular Junction Disorders

2015 ◽  
Author(s):  
Anthony A Amato ◽  
Mohammad Kian Salajegheh
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Motor Nerve ◽  
Neuromuscular Disorders ◽  
Synaptic Cleft ◽  
Organophosphate Poisoning ◽  
Electric Currents ◽  
Repetitive Nerve Stimulation ◽  
Congenital Myasthenic Syndromes ◽  
Myasthenic Syndromes

The three main components of the neuromuscular junction (NMJ) include the presynaptic region, the synaptic cleft, and the postsynaptic region. The NMJ acts as an interface between the motor nerve and muscle by converting the motor nerve electric currents into chemical signals and then back into electric currents in the muscle. This chapter reviews electrodiagnostic testing in NMJ disorders, including repetitive nerve stimulation and single-fiber electromyography. Myasthenia gravis, congenital myasthenic syndromes, Lambert-Eaton myasthenic syndrome, botulism, and organophosphate poisoning and other toxins are discussed, including epidemiology, etiology/genetics, pathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis. Tables include an overview of neuromuscular disorders, drugs with adverse effects on the NMJ, common immunomodulatory agents used for treatment of myasthenia gravis, congenital myasthenic syndromes, and toxins and venoms. Figures illustrate the NMJ structure and function, structure of the presynaptic and postsynaptic regions, electrodiagnostic studies in NMJ disorders, and dysfunction of the NMJ in acetylcholine receptor myasthenia gravis. This review contains 5 highly rendered figures, 5 tables, and 65 references.

Neuromuscular Junction Disorders

2015 ◽  
Author(s):  
Anthony A Amato ◽  
Mohammad Kian Salajegheh
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Motor Nerve ◽  
Neuromuscular Disorders ◽  
Synaptic Cleft ◽  
Organophosphate Poisoning ◽  
Electric Currents ◽  
Repetitive Nerve Stimulation ◽  
Congenital Myasthenic Syndromes ◽  
Myasthenic Syndromes

The three main components of the neuromuscular junction (NMJ) include the presynaptic region, the synaptic cleft, and the postsynaptic region. The NMJ acts as an interface between the motor nerve and muscle by converting the motor nerve electric currents into chemical signals and then back into electric currents in the muscle. This chapter reviews electrodiagnostic testing in NMJ disorders, including repetitive nerve stimulation and single-fiber electromyography. Myasthenia gravis, congenital myasthenic syndromes, Lambert-Eaton myasthenic syndrome, botulism, and organophosphate poisoning and other toxins are discussed, including epidemiology, etiology/genetics, pathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis. Tables include an overview of neuromuscular disorders, drugs with adverse effects on the NMJ, common immunomodulatory agents used for treatment of myasthenia gravis, congenital myasthenic syndromes, and toxins and venoms. Figures illustrate the NMJ structure and function, structure of the presynaptic and postsynaptic regions, electrodiagnostic studies in NMJ disorders, and dysfunction of the NMJ in acetylcholine receptor myasthenia gravis. This review contains 5 highly rendered figures, 5 tables, and 65 references.

Congenital myasthenic syndromes in the Thai population: Clinical findings and novel mutations

2020 ◽  
Vol 30 (10) ◽  
pp. 851-858
Author(s):  
Nalinee Pattrakornkul ◽  
Chupong Ittiwut ◽  
Ponghatai Boonsimma ◽  
Kanokwan Boonyapisit ◽  
Chaiyos Khongkhatithum ◽  
...  
Keyword(s):  
Clinical Findings ◽  
Novel Mutations ◽  
Thai Population ◽  
Congenital Myasthenic Syndromes ◽  
Myasthenic Syndromes

scholarly journals Targeted therapies for congenital myasthenic syndromes: systematic review and steps towards a treatabolome

2019 ◽  
Vol 3 (1) ◽  
pp. 19-37 ◽  
Author(s):  
Rachel Thompson ◽  
Gisèle Bonne ◽  
Paolo Missier ◽  
Hanns Lochmüller
Keyword(s):  
Systematic Review ◽  
Genetic Diseases ◽  
Genetic Defect ◽  
Genetic Diagnosis ◽  
Neuromuscular Diseases ◽  
Congenital Myasthenic Syndromes ◽  
Rare Genetic Diseases ◽  
Computer Aided ◽  
Receive Treatment ◽  
Myasthenic Syndromes

Abstract Despite recent scientific advances, most rare genetic diseases — including most neuromuscular diseases — do not currently have curative gene-based therapies available. However, in some cases, such as vitamin, cofactor or enzyme deficiencies, channelopathies and disorders of the neuromuscular junction, a confirmed genetic diagnosis provides guidance on treatment, with drugs available that may significantly alter the disease course, improve functional ability and extend life expectancy. Nevertheless, many treatable patients remain undiagnosed or do not receive treatment even after genetic diagnosis. The growth of computer-aided genetic analysis systems that enable clinicians to diagnose their undiagnosed patients has not yet been matched by genetics-based decision-support systems for treatment guidance. Generating a ‘treatabolome’ of treatable variants and the evidence for the treatment has the potential to increase treatment rates for treatable conditions. Here, we use the congenital myasthenic syndromes (CMS), a group of clinically and genetically heterogeneous but frequently treatable neuromuscular conditions, to illustrate the steps in the creation of a treatabolome for rare inherited diseases. We perform a systematic review of the evidence for pharmacological treatment of each CMS type, gathering evidence from 207 studies of over 1000 patients and stratifying by genetic defect, as treatment varies depending on the underlying cause. We assess the strength and quality of the evidence and create a dataset that provides the foundation for a computer-aided system to enable clinicians to gain easier access to information about treatable variants and the evidence they need to consider.

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