Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders caused by a failure of transmission at the neuromuscular junction (NMJ). They can be diverse in presentation, and the causative mutation can be in any one of over 30 genes involved in the development, function, and maintenance of the NMJ (Thompson et al., 2019). There are many ways to classify CMS, including by gene, protein location, responsiveness to treatment, or associated pathway (ENMC 260th workshop study group, 2023, Beeson, 2024). While the classification may help direct treatment strategies, the exact genetic cause is paramount to effective treatment. The prevalence of CMS varies between populations and may be lower or higher depending on the presence of founder mutations and the rate of consanguinity, but is thought to range from 1.8 to 14.8 per million (Parr et al., 2014, Troha Gergeli et al., 2020, Natera-de Benito et al., 2017). Although, estimates may be low as many patients remain un or misdiagnosed.

In this review we will describe some of the common, and less common presentations of CMS with a view to guiding the consulting clinician to the most appropriate diagnostic tests. Following a description of these tests we provide information on the most common treatment approaches for patients and highlight some exciting therapies that may soon be coming to clinics.