Congenital myasthenic syndromes: a difficult approach to diagnosis and therapy

Congenital myasthenic syndromes (CMS) are rare, genetically and clinically heterogeneous disorders of the neuromuscular junction. Most patients are symptomatic before the age of 2 years. Exact prevalence data are not available, but CMS are rare (approximately 2,000 to 3,000 patients worldwide).

Diagnosis of CMS (Chat mutation) was made in a 20-month-old child due to recurrent apnea and life-threatening events. Clinical presentation may vary from weakness and exercise intolerance to severe symptoms in the newborn period such as a floppy infant with additional bulbar weakness and respiratory insufficiency. Other symptoms often observed are ptosis, ophthalmoplegia, suck, and swallowing difficulties. Respiratory infections may lead to life-threatening events and death.

AChR antibodies in CMS are expected to be negative. Typical clinical symptoms and response to ACHE inhibitors lead to noninvasive genetic testing. The exact diagnosis is extremely important to start early appropriate therapy to prevent life-threatening events and improve the clinical course. Most patients are eligible for drug therapy with esterase inhibitors or/and 3,4-diaminopyridine. The precise molecular diagnosis and genetic counseling are important for patients and their caregivers.