Abstract
Congenital myasthenic syndromes (CMS) have some phenotypic overlap with seronegative myasthenia gravis (SNMG). The aim of this single center study was to assess the minimum occurrence of CMS misdiagnosed as double SNMG in a Brazilian cohort. The genetic analysis of the most common mutations in CHRNE, RAPSN, and DOK7 genes was used as the main screening tool. We performed genetic analysis in 22 patients with a previous diagnosis of 'double' SNMG. In this study, one CMS patient was confirmed due to the presence of compound heterozygous variants in the CHRNE gene (c.130insG/p.Cys210Phe). This study confirmed that CMS due to CHNRE mutations can be mistaken for SNMG. In addition, our study estimated the prevalence of misdiagnosed CMS to be 4.5% in 'double' SNMG patients of our center. Based on our findings, genetic screening could be helpful in the diagnostic workup of patients with 'double' SNMG in whom differential diagnosis is recommended.
Highlights
Congenital myasthenic syndromes (CMS) are heterogeneous inherited diseases caused by specific mechanisms that compromise the function of neuromuscular transmission[1,2]
We found 22 patients with ‘double’ seronegative myasthenia gravis (SNMG) from unrelated families in our center who were eligible for genetic screening for CMS
It is well-established that CMS is a differential diagnosis of MG, mainly for SNMG and pediatric MG3,8-10
Summary
Congenital myasthenic syndromes (CMS) are heterogeneous inherited diseases caused by specific mechanisms that compromise the function of neuromuscular transmission[1,2]. An abnormal decrement on low-frequency repetitive nerve stimulation (RNS) or an increased jitter on single-fibre electromyography (SFEMG) confirms an underlying neuromuscular transmission defect in CMS, but these electrodiagnostic findings are similar to those in MG6,7. This fact makes it difficult to electrophysiologically differentiate CMS from MG6,7. The presence of serum antibodies, e.g. anti-acetylcholinesterase receptor (AChR), is helpful to distinguish between the diseases This situation is still challenging, especially if the initial diagnosis is seronegative MG (SNMG), which is usually one cause of the delay in the CMS diagnosis in pediatric and adult populations[4,5,6,8,9]. Genetic screening could be helpful in the diagnostic workup of patients with ‘double’ SNMG in whom differential diagnosis is recommended
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