Diagnosis
Congenital myasthenic syndrome (CMS) is "often difficult to diagnose because of a broad differential diagnosis and lack of specific laboratory findings. Identification of the underlying mutation is critical, as certain mutations lead to treatment-responsive conditions while others do not." Whole exome sequencing (WES) is often used as a diagnostic tool that allows for the "initiation of specific treatment". Management
Treatment depends on the form (category) of the disease. Although symptoms are similar to myasthenia gravis, treatments used in MG are not useful in CMS. MG is treated with immunosuppressants, but CMS is not an autoimmune disorder. Instead, CMS is genetic and responds to other forms of drug treatments. A form of presynaptic CMS is caused by an insufficient release of acetylcholine (ACh) and is treated with cholinesterase inhibitors.Postsynaptic fast-channel CMS, in which ACh receptors do not stay open long enough, is treated with cholinesterase inhibitors and 3,4-diaminopyridine. In the U.S., the more stable phosphate salt formulation of 3,4-diaminopyridine (amifampyridine phosphate) is under development as an orphan drug for CMS and is available to eligible patients at no cost under an expanded access program. Postsynaptic slow-channel CMS is treated with quinidine or fluoxetine, which blocks the ACh receptor.Ephedrine, a β(2)-adrenergic receptor agonist with alpha activity,  has been tested on patients in clinical trials and appears to be an effective treatment for DOK7 CMS. Most patients tolerate this type of treatment and improvements in strength can be substantial.
Rapsyn interacts directly with the AChRs and plays a vital role in agrin-induced clustering of the AChR. Without rapsyn, functional synapses cannot be created, as the membrane folds do not form properly. Patients with CMS-related mutations of the rapsyn protein typically are either homozygous for N88K or heterozygous for N88K and a second mutation. The major effect of the mutation N88K in rapsyn is to reduce the stability of AChR clusters. The second mutation can be a determining factor in the severity of the disease.Studies have shown that most patients with CMS that have rapsyn mutations carry the common mutation N88K on at least one allele. However, research has revealed that there is a small population of patients who do not carry the N88K mutation on either of their alleles, but instead have different mutations of the RAPSN gene that codes for rapsyn on both of their alleles. Two novel missense mutations that have been found are R164C and L283P; the result is a decrease in co-clustering of AChR with raspyn. A third mutation is the intronic base alteration IVS1-15C>A, which causes abnormal splicing of RAPSN RNA. These results show that diagnostic screening for CMS mutations of the RAPSN gene cannot be based exclusively on the detection of N88K mutationsDok-7 is a postsynaptic protein that binds and activates MuSK protein, which then leads to AChR clustering and typical folding of the postsynaptic membrane. Mutations of Dok-7 are yrt another underlying mechanism of postsynaptic CMS.