Congenital Myasthenic Syndrome From a Single Center: Phenotypic and Genotypic features

Area of Science:

• Neurology
• Genetics
• Pediatrics

Background:

• Congenital myasthenic syndrome (CMS) comprises rare genetic disorders impacting neuromuscular junction transmission.
• Patients exhibit variable ocular, bulbar, respiratory, and extremity weakness, with potential response to symptomatic therapies.

Purpose of the Study:

• To characterize the demographic profile, clinical features, genetic variants, and treatment outcomes of 18 pediatric patients with CMS.
• To highlight the diagnostic delay and therapeutic responses across different genetic subtypes of CMS.

Main Methods:

• Retrospective chart review of 18 patients diagnosed with CMS over a decade at a pediatric neuromuscular center.
• Analysis of clinical presentation, genetic subtypes, treatment interventions, and follow-up data.

Main Results:

• Identified 10 distinct genetic subtypes of CMS, with CHRNE being the most frequent (6 patients).
• Observed generalized fatigable weakness affecting ocular, bulbar, and extremity muscles, with significant diagnostic delays.
• Pyridostigmine improved most patients, but some subtypes worsened; albuterol, ephedrine, or 3,4-diaminopyridine were beneficial for others.

Conclusions:

• Increased recognition of CMS is vital for earlier diagnosis and timely intervention.
• Genetic testing is essential for identifying novel variants and understanding the expanding phenotype of congenital myasthenic syndromes.