Muscle Biopsy Findings in Valosin-Containing Protein Multisystem Proteinopathy.

Background And Objectives: Valosin Containing Protein-associated multisystem proteinopathy (VCP-MSP) is a progressive, autosomal dominant disorder caused by pathogenic variants in the VCP gene, resulting in a heterogeneous clinical presentation. Muscle biopsy findings are characteristic but not pathognomonic. This study aimed to comprehensively analyse VCP-related myopathology and explore correlations with clinical phenotypes, genetic variants, and disease progression.

Improving Examination Skills in Neuromuscular Disorders Through an Educational Video.

Background: The acquisition of practical skills is a key objective of medical education. Improving knowledge and skills is essential for early diagnosis of patients suffering from neuromuscular (NM) diseases.

Approach: Multimedia tools have proved to be useful and effective for learning clinical skills.

-related myopathies: clinical, myopathological and genotypic spectrum in a multicentre French cohort.

Background: Myosin heavy chain 7 ()-related myopathies (-RMs) are a group of muscle disorders linked to pathogenic variants in the gene, encoding the slow/beta-cardiac myosin heavy chain, which is highly expressed in skeletal muscle and heart. The phenotype is heterogeneous including distal, predominantly axial or scapuloperoneal myopathies with variable cardiac involvement.

Methods: We retrospectively analysed the clinical, muscle MRI, genetic and myopathological features of 57 patients.

Diagnostic yield of a practical electrodiagnostic protocol discriminating between different congenital myasthenic syndromes.

Congenital myasthenic syndromes (CMS) are a group of heterogeneous diseases of the neuromuscular junction. We report electrodiagnostic testing (EDX) and genetic findings in a series of 120 CMS patients tested with a simple non-invasive EDX workup with surface recording of CMAPs and 3Hz repetitive nerve stimulation of accessory, radial and deep fibular nerves. Five ENMG phenotypes were retrieved based on the presence or not of R-CMAPs and the distribution pattern of decremental CMAP responses which significantly correlated with genetic findings (p <0.

LAMA2-Related Muscular Dystrophy: The Importance of Accurate Phenotyping and Brain Imaging in the Diagnosis of LGMD.

We report three siblings from a non-consanguineous family presenting with contractural limb-girdle phenotype with intrafamilial variability. Muscle MRI showed posterior thigh and quadriceps involvement with a sandwich-like sign. Whole-exome sequencing identified two compound heterozygous missense TTN variants and one heterozygous LAMA2 variant.

Genotype-phenotype correlations in valosin-containing protein disease: a retrospective muticentre study.

Background: Valosin-containing protein (VCP) disease, caused by mutations in the gene, results in myopathy, Paget's disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype-phenotype correlation data are limited. This study characterises patients with mutations in gene and investigates genotype-phenotype correlations.

Phenotypical variability and atypical presentations in a French cohort of Andersen-Tawil syndrome.

Background And Purpose: Andersen-Tawil syndrome (ATS) is a skeletal muscle channelopathy caused by KCNJ2 mutations, characterized by a clinical triad of periodic paralysis, cardiac arrhythmias and dysmorphism. The muscle phenotype, particularly the atypical forms with prominent permanent weakness or predominantly painful symptoms, remains incompletely characterized.

Methods: A retrospective clinical, histological, electroneuromyography (ENMG) and genetic analysis of molecularly confirmed ATS patients, diagnosed and followed up at neuromuscular reference centers in France, was conducted.

A multicenter cross-sectional French study of the impact of COVID-19 on neuromuscular diseases.

Background: Due to their health condition, patients with neuromuscular diseases (NMD) are at greater risk of developing serious complications with COVID-19. The objective of this study was to analyze the prevalence of COVID-19 among NMD patients and the risk factors for its impact and severity during the first wave of the pandemic. Clinical data were collected from NMD-COVID-19 patients, between March 25, 2020 and May 11, 2020 in an anonymous survey carried out by expert physicians from the French Health Care Network Filnemus.

Clinical and Molecular Spectrum Associated with COL6A3 c.7447A>G p.(Lys2483Glu) Variant: Elucidating its Role in Collagen VI-related Myopathies.

Background: Dominant and recessive autosomal pathogenic variants in the three major genes (COL6A1-A2-A3) encoding the extracellular matrix protein collagen VI underlie a group of myopathies ranging from early-onset severe conditions (Ullrich congenital muscular dystrophy) to milder forms maintaining independent ambulation (Bethlem myopathy). Diagnosis is based on the combination of clinical presentation, muscle MRI, muscle biopsy, analysis of collagen VI secretion, and COL6A1-A2-A3 genetic analysis, the interpretation of which can be challenging.

Objective: To refine the phenotypical spectrum associated with the frequent COL6A3 missense variant c.

[Limb-Girdle Muscular Dystrophy type R9 linked to the FKRP gene: state of the art and therapeutic perspectives].

Mutations in the FKRP gene encoding the fukutin-related protein (FKRP) cause a wide spectrum of myopathies, ranging from severe forms of congenital muscular dystrophies associated with structural abnormalities of the central nervous system, to exertional myalgia or asymptomatic hyperCKemia, and to a form of limb girdle muscular dystrophy, LGMD-R9, (ex-LGMD-2I). LGMD-R9 is characterized by a proximal girdle deficit predominantly in the lower limbs to start with, with respiratory and cardiac damage that may affect the vital prognosis. Serum CK levels are markedly elevated and, on muscle biopsy, is detected a dystrophic formula associated with a reduction in the glycosylation of α-dystroglycan by immunostains and immunoblotting.

The clinical, histologic, and genotypic spectrum of -related myopathy: A case series.

Objective: To clarify the prevalence, long-term natural history, and severity determinants of -related myopathy (SEPN1-RM), we analyzed a large international case series.

Methods: Retrospective clinical, histologic, and genetic analysis of 132 pediatric and adult patients (2-58 years) followed up for several decades.

Results: The clinical phenotype was marked by severe axial muscle weakness, spinal rigidity, and scoliosis (86.

Muscular, Ocular and Brain Involvement Associated with a De Novo 11q13.2q14.1 Duplication: Contribution to the Differential Diagnosis of Muscle-Eye-Brain Congenital Muscular Dystrophy.

Muscular weakness and hypotonia may be associated with multisystem involvement giving rise to complex phenotypes, many of which are uncharacterized. We report a patient presenting with congenital hypotonia and severe ocular and brain abnormalities, evoking a Muscle Eye Brain disease (MEB). She had global muscular weakness, hypotonia and amyotrophy, joint hyperlaxity, kyphoscoliosis, respiratory insufficiency, dysmorphic features and severe intellectual disability.

ASC-1 Is a Cell Cycle Regulator Associated with Severe and Mild Forms of Myopathy.

Objective: Recently, the ASC-1 complex has been identified as a mechanistic link between amyotrophic lateral sclerosis and spinal muscular atrophy (SMA), and 3 mutations of the ASC-1 gene TRIP4 have been associated with SMA or congenital myopathy. Our goal was to define ASC-1 neuromuscular function and the phenotypical spectrum associated with TRIP4 mutations.

Methods: Clinical, molecular, histological, and magnetic resonance imaging studies were made in 5 families with 7 novel TRIP4 mutations.

SELENON (SEPN1) protects skeletal muscle from saturated fatty acid-induced ER stress and insulin resistance.

Selenoprotein N (SELENON) is an endoplasmic reticulum (ER) protein whose loss of function leads to a congenital myopathy associated with insulin resistance (SEPN1-related myopathy). The exact cause of the insulin resistance in patients with SELENON loss of function is not known. Skeletal muscle is the main contributor to insulin-mediated glucose uptake, and a defect in this muscle-related mechanism triggers insulin resistance and glucose intolerance.

Immununochemical Markers of the Amyloid Cascade in the Hippocampus in Motor Neuron Diseases.

Background: Several findings suggest that the amyloid precursor protein (APP) and the amyloid cascade may play a role in motor neuron disease (MND).

Objective: Considering that dementia is one of the most frequent non-motor symptoms in amyotrophic lateral sclerosis (ALS) and that hippocampus is one of the brain areas with greater presence of amyloid-related changes in neurodegenerative diseases, our aim was to analyze the molecular markers of the amyloid cascade of APP in pathology studies of the hippocampus of autopsied patients with ALS and ALS-frontotemporal dementia (FTD).

Methods: We included nine patients with MND and four controls.

Analysis of the Relationship between the Month of Birth and Risk of Multiple Sclerosis in a Spanish Population.

Background: Some studies have suggested an association between the month of birth and risk of multiple sclerosis (MS), related to environmental factors, mainly sun exposure and maternal vitamin D levels. Few studies have been conducted in Southern Europe countries. Madrid has a continental climate with considerable variation of sun hours between winter and summer, so it may be relevant to study this relationship.