scholarly journals Intrafamilial variation in clinical manifestations and response to salbutamol in siblings with congenital myasthenic syndrome caused by DOK7 mutations

2019 ◽  
Author(s):  
Trupti Jadhav ◽  
Poornima Shah ◽  
Purva Keni Karnavat ◽  
Anaita Udwadia Hegde
Keyword(s):  
Neuromuscular Junction ◽  
Early Life ◽  
Conventional Treatment ◽  
Clinical Manifestations ◽  
Respiratory Muscles ◽  
Congenital Myasthenic Syndrome ◽  
Late Childhood ◽  
Genetic Defects ◽  
Myasthenic Syndrome ◽  
Myasthenic Syndromes

The congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders arising from genetic defects in presynaptic, synaptic, and postsynaptic proteins of the neuromuscular junction (NMJ) resulting in variable and characteristically fatigable muscle weakness affecting limb, ocular, bulbar, trunk, and respiratory muscles from early life. DOK7 mutation resulting in synaptic and postsynaptic CMS clinically presents with limb-girdle myasthenia with sparing of facial and EOM. They characteristically worsen with conventional treatment and show excellent response to salbutamol/ ephedrine. Here we present a case highlighting a varied presentation beginning in late childhood and its evolution to reveal its congenital nature and subsequent management with salbutamol.

scholarly journals Congenital Myasthenic Syndrome: A Rare, Potentially Treatable Cause of Respiratory Failure in a “Floppy” Infant

2000 ◽  
Vol 28 (1) ◽  
pp. 82-86
Author(s):  
P. P. McConkey ◽  
A. J. Mullens
Keyword(s):  
Cerebral Palsy ◽  
Intensive Care ◽  
Respiratory Failure ◽  
Neuromuscular Junction ◽  
Muscle Weakness ◽  
Congenital Myasthenic Syndrome ◽  
General Level ◽  
Floppy Infant ◽  
Myasthenic Syndrome ◽  
Myasthenic Syndromes

A four-month-old infant, thought to suffer from cerebral palsy, presented with respiratory failure on the background of a gradually deteriorating general level of function. Whilst being ventilated in intensive care he was noted to have severe muscle weakness. A disorder of the neuromuscular junction was suspected and he was subsequently demonstrated to have a congenital myasthenic syndrome. Anticholinesterase therapy produced a dramatic recovery. The congenital myasthenic syndromes and the diagnosis of a “floppy baby” are briefly reviewed.

scholarly journals Regulation of the Rapsyn Promoter by Kaiso and δ-Catenin

2004 ◽  
Vol 24 (16) ◽  
pp. 7188-7196 ◽  
Author(s):  
Marianna Rodova ◽  
Kevin F. Kelly ◽  
Michael VanSaun ◽  
Juliet M. Daniel ◽  
Michael J. Werle
Keyword(s):  
Transcription Factor ◽  
Neuromuscular Junction ◽  
Acetylcholine Receptors ◽  
Consensus Sequence ◽  
Specific Protein ◽  
C2c12 Cells ◽  
Congenital Myasthenic Syndrome ◽  
P120 Catenin ◽  
Myasthenic Syndrome

ABSTRACT Rapsyn is a synapse-specific protein that is required for clustering acetylcholine receptors at the neuromuscular junction. Analysis of the rapsyn promoter revealed a consensus site for the transcription factor Kaiso within a region that is mutated in a subset of patients with congenital myasthenic syndrome. Kaiso is a POZ-zinc finger family transcription factor which recognizes the specific core consensus sequence CTGCNA (where N is any nucleotide). Previously, the only known binding partner for Kaiso was the cell adhesion cofactor, p120 catenin. Here we show that δ-catenin, a brain-specific member of the p120 catenin subfamily, forms a complex with Kaiso. Antibodies against Kaiso and δ-catenin recognize proteins in the nuclei of C2C12 myocytes and at the postsynaptic domain of the mouse neuromuscular junction. Endogenous Kaiso in C2C12 cells coprecipitates with the rapsyn promoter in vivo as shown by chromatin immunoprecipitation assay. Minimal promoter assays demonstrated that the rapsyn promoter can be activated by Kaiso and δ-catenin; this activation is apparently muscle specific. These results provide the first experimental evidence that rapsyn is a direct sequence-specific target of Kaiso and δ-catenin. We propose a new model of synapse-specific transcription that involves the interaction of Kaiso, δ-catenin, and myogenic transcription factors at the neuromuscular junction.

Evaluation of the neuromuscular junction in a middle‐aged mouse model of congenital myasthenic syndrome

2019 ◽  
Vol 60 (6) ◽  
pp. 790-800
Author(s):  
Luana Pereira Leite Schetino ◽  
Matheus Fonseca ◽  
Matheus Proença Simão Magalhães Gomes ◽  
Priscila Aparecida Costa Valadão ◽  
Wallace Lucio Camargo ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Mouse Model ◽  
Congenital Myasthenic Syndrome ◽  
Aged Mouse ◽  
Middle Aged ◽  
Myasthenic Syndrome

Immune-Mediated Disease of the Neuromuscular Junction

2019 ◽  
pp. 130-176
Author(s):  
Robert P. Lisak ◽  
James Selwa
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Rare Disease ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Diagnosis And Treatment ◽  
Future Directions ◽  
Immune Mediated ◽  
Myasthenic Syndrome

The chapter is concerned with disorders that affect the neuromuscular junction (NMJ). Myasthenia gravis (MG) is a prototypic antibody-mediated disease affecting the neuromuscular junction. The chapter looks at the epidemiology of MG. It also considers clinical manifestations and presentations, classification and staging, and diagnosis. The chapter also examines immunologic testing and issues such as pregnancy in MG. It considers future directions and treatment options in this area. Next, the chapter considers Lambert Eaton myasthenic syndrome (LEMS), which is a rare disease of the NMJ that is difficult to diagnose. The chapter looks at clinical manifestations, diagnosis, and treatment. Finally, the chapter briefly considers other immune-mediated diseases.

Neuromuscular junction immaturity and muscle atrophy are hallmarks of the ColQ‐deficient mouse, a model of congenital myasthenic syndrome with acetylcholinesterase deficiency

2016 ◽  
Vol 30 (6) ◽  
pp. 2382-2399 ◽  
Author(s):  
Séverine M. Sigoillot ◽  
Francine Bourgeois ◽  
Jennifer Karmouch ◽  
Jordi Molgó ◽  
Alexandre Dobbertin ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Muscle Atrophy ◽  
Congenital Myasthenic Syndrome ◽  
Deficient Mouse ◽  
Myasthenic Syndrome

scholarly journals The spectrum of mutations that underlie the neuromuscular junction synaptopathy in DOK7 congenital myasthenic syndrome

2012 ◽  
Vol 21 (17) ◽  
pp. 3765-3775 ◽  
Author(s):  
Judith Cossins ◽  
Wei Wei Liu ◽  
Katsiaryna Belaya ◽  
Susan Maxwell ◽  
Michael Oldridge ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Congenital Myasthenic Syndrome ◽  
Myasthenic Syndrome

Pathogenic Mechanisms and Clinical Correlations in Autoimmune Myasthenic Syndromes

2018 ◽  
Vol 38 (03) ◽  
pp. 344-354 ◽  
Author(s):  
Hakan Cetin ◽  
Angela Vincent
Keyword(s):  
Neuromuscular Junction ◽  
Protein Interactions ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Protein Protein Interactions ◽  
Pathogenic Mechanisms ◽  
Density Lipoprotein Receptor ◽  
Myasthenic Syndrome ◽  
Functional Blocking ◽  
Myasthenic Syndromes

AbstractAutoimmune myasthenic syndromes are antibody-mediated disorders of the neuromuscular junction. Common antigenic targets are the acetylcholine receptor or muscle specific kinase (MuSK) in myasthenia gravis (MG) and the voltage-gated calcium channel in Lambert-Eaton myasthenic syndrome. There is evidence that antibodies directed against other antigens such as low-density lipoprotein receptor-related protein 4 (LRP4) are also involved in MG. The mechanisms by which various antibodies exert their pathogenic effect depend on the IgG subclass and also the epitope location on the antigens. These mechanisms are partly heterogeneous and include antigen degradation, complement activation, direct functional blocking, or disruption of protein–protein interactions. The neuromuscular junction is characterized by a structural and functional plasticity that is able to compensate for some of the neuromuscular junction defects. Here, we discuss the underlying pathogenic mechanisms of the different autoantibodies and correlate them with phenotypic features. The understanding of these elements should help guide the clinical management of patients with autoimmune myasthenic syndromes.

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