Congenital myasthenia is a group of disorders caused by a biochemical defect or a structural alteration of the neuromuscular junction that leads to a clinical picture of muscle weakness and fatigability from birth or early infancy. It is important to distinguish these forms of the disease from myasthenia gravis (a disorder of autoimmune origin) and neonatal myasthenia (in children of mothers with myasthenia gravis).
The prevalence of congenital myasthenic syndromes has been estimated between 1/500 000 (GeneReviews) and 9.2/1 000 000 (Parr et al., 2014). Its etiology is largely genetic. As of today, several involved genes are known, allowing for two thirds of cases to have a positive genetic diagnosis (Jacob et al., 2009).
The most frequently involved genes and their diagnostic yields are CHRNE (50%), RAPSN (15-20%), COLQ (10-15%), DOK7 (10-15%), CHAT (5%), and GFPT1 (2%). The core panel includes these six genes, and we have also developed a comprehensive panel with 23 related genes that will allow optimizing the diagnostic yield.