An observational longitudinal study of congenital myasthenic syndromes.

Congenital Myasthenic Syndromes (CMS) are a group of inherited disorders characterised by fatigable muscle weakness. There are currently no validated outcome measures in CMS. We conducted a prospective exploratory observational study in 49 CMS patients.

Epidemiology and 10-year clinical care of juvenile myasthenia gravis in England: a retrospective cohort study.

Background: Published evidence is limited on the clinical burden of juvenile myasthenia gravis (JMG). We aimed to assess epidemiology and the clinical characteristics of JMG in England.

Methods: We performed a retrospective analysis of patients with newly diagnosed JMG identified in England via primary care and hospital data between 2010 and 2019.

Neonatal encephalopathy: when the diagnosis is not hypoxic ischaemic encephalopathy.

Neonatal encephalopathy (NE) presents as reduced consciousness, often with seizures, abnormal tone, feeding and respiratory difficulties. The most common cause is secondary to a hypoxic-ischaemic event. However, there are many important diagnoses that can also present as NE, so-called 'hypoxic ischaemic encephalopathy (HIE) mimics'.

Assessing the Utility of ColabFold and AlphaMissense in Determining Missense Variant Pathogenicity for Congenital Myasthenic Syndromes.

Background/objectives: Congenital myasthenic syndromes (CMSs) are caused by variants in >30 genes with increasing numbers of variants of unknown significance (VUS) discovered by next-generation sequencing. Establishing VUS pathogenicity requires in vitro studies that slow diagnosis and treatment initiation. The recently developed protein structure prediction software AlphaFold2/ColabFold has revolutionized structural biology; such predictions have also been leveraged in AlphaMissense, which predicts ClinVar variant pathogenicity with 90% accuracy.

Congenital myasthenic syndromes: increasingly complex.

Purpose Of Review: Congenital myasthenia syndromes (CMS) are treatable, inherited disorders affecting neuromuscular transmission. We highlight that the involvement of an increasing number of proteins is making the understanding of the disease mechanisms and potential treatments progressively more complex.

Recent Findings: Although early studies identified mutations of proteins directly involved in synaptic transmission at the neuromuscular junction, recently, next-generation sequencing has facilitated the identification of many novel mutations in genes that encode proteins that have a far wider expression profile, some even ubiquitously expressed, but whose defective function leads to impaired neuromuscular transmission.

Long term outcome in non-multiple sclerosis paediatric acquired demyelinating syndromes.

Objectives: We aimed to study the risks of relapse and long term disability in children with non-MS acquired demyelinating syndromes (ADS).

Methods: In this prospective, multi-centre study, from the 14 UK pediatric neurology centres, children (<16 years) experiencing a first episode of ADS were recruited from 2010 to 2014. Case report forms were collected prospectively.

Treatment Options in Spinal Muscular Atrophy: A Pragmatic Approach for Clinicians.

Spinal muscular atrophy (SMA) is a rare neurodegenerative neuromuscular disorder with a wide phenotypic spectrum of severity. SMA was previously life limiting for patients with the most severe phenotype and resulted in progressive disability for those with less severe phenotypes. This has changed dramatically in the past few years with the approvals of three disease-modifying treatments.

A study of referral bias in NMOSD and MOGAD cohorts.

Background: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are rare disorders often seen in highly specialized services or tertiary centres. We aimed to assess if cohort characteristics depend on the origin of the referral catchment areas serviced by our centre (i.e.

Congenital myasthenic syndromes: a retrospective natural history study of respiratory outcomes in a single centre.

Respiratory problems are a major cause of morbidity and mortality in patients with congenital myasthenic syndromes, a rare heterogeneous group of neuromuscular disorders caused by genetic defects impacting the structure and function of the neuromuscular junction. Recurrent, life-threatening episodic apnoea in early infancy and childhood and progressive respiratory failure requiring ventilation are features of certain genotypes of congenital myasthenic syndromes. Robb published empirical guidance on respiratory management of the congenital myasthenic syndromes, but other than this workshop report, there are little published longitudinal natural history data on respiratory outcomes of these disorders.

Expanding the phenotype of DYNC1H1-associated diseases with a rare variant resulting in spinal muscular atrophy with lower extremity predominance (SMA-LED) and upper motor neuron signs.

Background: Spinal muscular atrophy with lower extremity predominance (SMA-LED) is an autosomal dominant disorder. Since SMA-LED affects lower motor neurons, the disease is characterized by weakness and atrophy of lower limb muscles. We present a familial case series of SMA-LED with upper motor neuron signs associated with a rare variant in DYNC1H1.

Do Early Relapses Predict the Risk of Long-Term Relapsing Disease in an Adult and Paediatric Cohort with MOGAD?

Objective: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can be monophasic or relapsing, with early relapse being a feature. However, the relevance of early relapse on longer-term relapse risk is unknown. Here, we investigate whether early relapses increase longer-term relapse risk in patients with MOGAD.

Care Recommendations for the Investigation and Management of Children With Skeletal Muscle Channelopathies.

The field of pediatric skeletal muscle channelopathies has seen major new advances in terms of a wider understanding of clinical presentations and new phenotypes. Skeletal muscle channelopathies cause significant disability and even death in some of the newly described phenotypes. Despite this, there are virtually no data on the epidemiology and longitudinal natural history of these conditions or randomized controlled trial evidence of efficacy or tolerability of any treatment in children, and thus best practice care recommendations do not exist.

Antineurofascin IgG2-associated paediatric autoimmune nodopathy.

In this case series of four paediatric patients, we present the first described cases of immunotherapy-responsive autoimmune nodopathy with IgG2 antineurofascin antibodies. In three cases, the antineurofascin antibodies were predominantly of the IgG2 subclass, a novel finding in comparison to previously described adult cases where IgG4 and/or IgG1/3 have typically been described. One patient had low signal for IgG2 with predominant IgG1 and IgG4 antibodies, a pattern commonly seen in adult patients.

Expanding the phenotype of children presenting with hypoventilation with biallelic TBCK pathogenic variants and literature review.

Individuals with biallelic TBCK pathogenic variants present in infancy with distinctive facial features, profound hypotonia, severe intellectual impairment and epilepsy. Although rare, it may mimic other neurogenetic disorders leading to extensive investigations. Improved understanding of the clinical phenotype can support early monitoring of complications due to respiratory insufficiency.

Muscle cramps and contractures: causes and treatment.

Muscle cramps are painful, sudden, involuntary muscle contractions that are generally self-limiting. They are often part of the spectrum of normal human physiology and can be associated with a wide range of acquired and inherited causes. Cramps are only infrequently due to progressive systemic or neuromuscular diseases.

SARS-CoV-2 vaccination and new-onset myasthenia gravis: A report of 7 cases and review of the literature.

Myasthenia gravis (MG) is an antibody-mediated immune disorder of the neuromuscular junction. SARS-CoV-2 is now recognised as a trigger factor for autoimmune diseases and to cause immune-mediated dysregulation, likely due to molecular mimicry induced by viral antigens. SARS-CoV-2 vaccination, similarly, results in exposure to viral antigen.