Diagnostic struggles in congenital myasthenic syndromes in children

Abstract

Congenital myasthenic syndromes (CMS) cover a group of heterogeneous disorders in which the neuromuscular transmission is affected. We diagnosed CMS in nine unrelated patients in the Netherlands. Six mutations were discovered in the acetylcholine receptor epsilon subunit gene, two in the receptor-associated protein of the synapse gene and one mutation in dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1. We describe the diagnostic work up in these children and common diagnostic pitfalls that caused delay in diagnosis and treatment, such as the lack of specificity of clinical features, technical drawbacks of invasive testing in young children, non-specific changes in muscle histology and false negative results of electromyography. Early initiation of treatment and alternative treatment regimens can considerably improve the quality of life of patients with CMS.

Keywords

Congenital myasthenic syndrome - RAPSN - CHRNE - DPAGT1 - phenotype - genotype - slow channel syndrome - acetylcholine receptor deficiency - neuromuscular junction