Relevance of muscle biopsies in the neonatal and early infantile period: a 52 years retrospective study in the gene-sequencing era.

Neuromuscular disorders (NMD) with neonatal or early infantile onset are usually severe and differ in symptoms, complications, and treatment options. The establishment of a diagnosis relies on the combination of clinical examination, morphological analyses of muscle biopsies, and genetic investigations. Here, we re-evaluated and classified a unique collection of 535 muscle biopsies from NMD infants aged 0-6 months examined over a period of 52 years.

Sporadic Late-Onset Nemaline Rod Myopathy: An Interesting Case.

Sporadic late-onset nemaline rod myopathy is a rare, acquired, sub-acute, adult-onset myopathy characterized by proximal muscle weakness and nemaline rods in the myofibers. In contrast to its congenital form, the prevalence in adult population is comparatively rare. Herein, we report a case of 60-year-old male who presented with insidious onset proximal muscle weakness with myopathic pattern on electromyography.

Congenital Titinopathies Linked to Mutations in Metatranscript-Only Exons.

Congenital titinopathies reported to date show autosomal recessive inheritance and are caused by a variety of genomic variants, most of them located in metatranscript (MTT)-only exons. The aim of this study was to describe additional patients and establish robust genotype-phenotype associations in titinopathies. This study involved analyzing molecular, clinical, pathological, and muscle imaging features in 20 patients who had at least one pathogenic or likely pathogenic variant in MTT-only exons, with onset occurring antenatally or in the early postnatal stages.

The Causality Spectrum of Dropped Head Syndrome is Broad and Includes Myopathy, Neurodegenerative Disorders, and Varia.

Dropped head syndrome is a common complication of various neurological disorders. Most commonly, dropped head syndrome is due to primary or secondary myopathy. However, neurodegenerative diseases and various other conditions can also be complicated by dropped head syndrome.

Bi-allelic MYMX variants cause a syndromic congenital myopathy with recognizable facial palsy, growth restriction, and dysmorphism.

Myogenic fusion, primarily regulated by the Myomaker and Myomixer proteins, is essential for skeletal muscle development, yet its mechanisms remain poorly understood. This study presents the clinical and molecular details of the third and fourth reported patients with biallelic variants in MYMX, the gene that encodes Myomixer. We identified a homozygous truncating variant [c.

Megaoesophagus associated to inflammatory infiltrate in the autonomous plexus in a 7-year-old Spanish Water Dog.

Background: Megaoesophagus (ME), a disorder of the oesophagus characterized by diffuse oesophageal dilation and decreased peristalsis that may be congenital or acquired. Knowledge regarding the aetiology and prognosis for canine acquired ME is currently limited with most cases being idiopathic, which is a considerable problem to implement an appropriate treatment and a potential better prognosis.

Case Presentation: A 7-year-old, neutered, female Spanish Water Dog was evaluated for progressive weight loss, chronic vomiting and regurgitation.

Phenotypic variability in congenital myasthenic syndrome with GFPT1 mutation.

Background: Congenital myasthenic syndrome (CMS) is phenotypically and genetically different from myasthenia gravis. CMS can present in adolescents and can be treatable. Genetic testing is helpful in diagnosis, and guides therapy, alleviating the need of muscle biopsy.

Segregation of the Variant (c.1817-3C>G) in a Consanguineous Saudi Family with Bethlem Myopathy.

Bethlem myopathy is a rare genetic disease caused by a variant mapped to 21q22, which harbors the collagen type VI alpha 2 chain and collagen type VI alpha 1 chain ( genes, and 2q37, which harbors the collagen type VI alpha 3 chain () gene. Disease onset can occur at any age, and the symptoms are related to those of muscular dystrophy. Since Bethlem myopathy is a rare disease, no previous studies have been conducted in Arab countries, including Saudi Arabia.

Restored Collagen VI Microfilaments Network in the Extracellular Matrix of CRISPR-Edited Ullrich Congenital Muscular Dystrophy Fibroblasts.

Collagen VI is an essential component of the extracellular matrix (ECM) composed by α1, α2 and α3 chains and encoded by , and genes. Dominant negative pathogenic variants in genes result in defects in collagen VI protein and are implicated in the pathogenesis of muscular diseases, including Ullrich congenital muscular dystrophy (UCMD). Here, we designed a CRISPR genome editing strategy to tackle a dominant heterozygous deletion c.

A Gain-of-Function Mutation in the Ca Channel ORAI1 Causes Stormorken Syndrome with Tubular Aggregates in Mice.

Store-operated Ca entry (SOCE) controls Ca homeostasis and mediates multiple Ca-dependent signaling pathways and cellular processes. It relies on the concerted activity of the reticular Ca sensor STIM1 and the plasma membrane Ca channel ORAI1. STIM1 and ORAI1 gain-of-function (GoF) mutations induce SOCE overactivity and excessive Ca influx, leading to tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK), two overlapping disorders characterized by muscle weakness and a variable occurrence of multi-systemic anomalies affecting spleen, skin, and platelets.

Gastruloids are competent to specify both cardiac and skeletal muscle lineages.

Cardiopharyngeal mesoderm contributes to the formation of the heart and head muscles. However, the mechanisms governing cardiopharyngeal mesoderm specification remain unclear. Here, we reproduce cardiopharyngeal mesoderm specification towards cardiac and skeletal muscle lineages with gastruloids from mouse embryonic stem cells.

[The influence of hydrokinesitherapy on motor and cardiorespiratory functions in hereditary myopathy of childhood].

Objective: To evaluate the impact of regular hydrokinesotherapy sessions and indicators of cardiorespiratory functions on the motor abilities of patients with hereditary myopathy of childhood.

Material And Methods: The study included 63 patients with genetically confirmed hereditary myopathy. Group 1 included 32 patients with Duchenne muscular dystrophy (DMD) who were in the early ambulatory stage.

Revision Surgery for Scar Contracture and Web Creep after Syndactyly Release.

Revision surgery after syndactyly separation is challenging. Web creep and scarring have a great impact on function and appearance of the hand. There is a paucity of literature on revision surgery for syndactyly.

[Tamoxifen, a high-potential molecule to treat all centronuclear myopathies].

Centronuclear myopathies are rare congenital disorders characterized by muscle weakness and mislocalization of organelles. The main genes associated to these muscle diseases are MTM1, DNM2, BIN1 and RYR1. To date, no therapy is available.

In a cohort of 961 clinically suspected Duchenne muscular dystrophy patients, 105 were diagnosed to have other muscular dystrophies (OMDs), with LGMD2E (variant SGCB c.544A>C) being the most common.

Background: Targeted next generation sequence analyses in a cohort of 961 previously described patients with clinically suspected Duchene muscular dystrophy (DMD) revealed that 145/961 (15%) had variants in genes associated with other muscular dystrophies (OMDs).

Methods: NGS was carried out in DMD negative patients after deletion/duplication analysis followed by WES for No variant cases.

Results: The majority of patients with OMDs had autosomal recessive diseases that included Limb-Girdle Muscular Dystrophies (LGMDs), Bethlem, Ullrich congenital Myopathies and Emery-Driefuss muscular dystrophy.

Camptodactyly.

Camptodactyly is a congenital difference with flexion contracture of the proximal interphalangeal (PIP) joint. Camptodactyly limited to one finger is believed to be due to an anomaly of the lumbrical muscle that inserts into the flexor digitorum superficialis (FDS) tendon instead of the extensor expansion, whereas multiple finger camptodactyly is believed to be a result of shortage of soft tissues on the flexor surface of the fingers. It is important to differentiate camptodactyly from other causes of extension lag at the PIP joint.

A Novel Splice Site Variant in COL6A1 Causes Ullrich Congenital Muscular Dystrophy in a Consanguineous Malian Family.

Background: Congenital muscular dystrophies (CMDs) are diverse early-onset conditions affecting skeletal muscle and connective tissue. This group includes collagen VI-related dystrophies such as Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM), caused by mutations in the COL6A1, COL6A2 and COL6A3 genes. We report a consanguineous Malian family with three siblings affected by UCMD due to a novel homozygous splice site variant in the COL6A1 gene.