Overview
Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders affecting neuromuscular transmission, leading to fluctuating muscle weakness and fatigability from infancy 1.Diagnosis
Genetic testing for mutations in genes involved in neuromuscular transmission, including NALCN 1.
Electromyography (EMG) showing decremental response to repetitive nerve stimulation 1.
Tensilon test may be positive but is nonspecific 1.
Muscle biopsy may reveal characteristic changes but is less commonly required 1.Management
First-line treatments: Cholinesterase inhibitors such as pyridostigmine, typically starting at 20-50 mg/kg/day in divided doses 1.
Adjunctive therapies: Immunosuppressive agents like prednisone or azathioprine for autoimmune overlap syndromes 1.
Supportive care: Respiratory support in severe cases, particularly those with autonomic instability 1.Special Populations
Pediatrics: Early diagnosis and management are crucial due to severe neonatal presentations and potential life-threatening episodes 1.
Comorbidities: Patients with CLIFAHDD syndrome (congenital contractures with hypotonia and developmental delay) may require multidisciplinary care addressing multiple systemic issues 1.Key Recommendations
Perform genetic testing focusing on NALCN mutations in infants presenting with congenital arthrogryposis and severe neuromuscular symptoms 1 (Evidence: Strong).
Initiate pyridostigmine as first-line therapy for symptomatic relief in CMS, adjusting dose based on response and side effects 1 (Evidence: Moderate).
Closely monitor patients for autonomic instability and provide appropriate respiratory support in severe cases 1 (Evidence: Expert opinion).References
1 Bend EG, Si Y, Stevenson DA, Bayrak-Toydemir P, Newcomb TM, Jorgensen EM et al.. NALCN channelopathies: Distinguishing gain-of-function and loss-of-function mutations. Neurology 2016. link
2 Sakai M, Saisu H, Koshigoe N, Abe T. Detergent-soluble form of acetylcholinesterase in the electric organ of electric rays. Its isolation, characterization and monoclonal antibodies. European journal of biochemistry 1985. link
3 Sikorav JL, Grassi J, Bon S. Synthesis in vitro of precursors of the catalytic subunits of acetylcholinesterase from Torpedo marmorata and Electrophorus electricus. European journal of biochemistry 1984. link