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.

Myasthenic syndromes: mistaking genetic for acquired.

Congenital myasthenic syndromes (CMS) are a rare, heterogeneous group of disorders caused by pathogenic variants in genes encoding proteins essential for neuromuscular transmission. variants are among the most common causes of CMS and one of the subtypes that may worsen with pyridostigmine. We report two patients who presented in adulthood with fatigable limb girdle weakness, initially diagnosed with seronegative myasthenia gravis, who slowly progressed over time despite escalating treatment and eventually needed intensive care admission.

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.