Introduction: Skeletal muscle channelopathies are rare inherited conditions that cause significant morbidity and impact on quality of life. Some subsets have a mortality risk. Improved genetic methodology and understanding of phenotypes has improved diagnostic accuracy and yield.
Areas covered: We discuss diagnostic advances since the advent of next generation sequencing and the role of whole exome and genome sequencing. Advances in genotype-phenotype-functional correlations have improved understanding of inheritance and phenotypes. We outline new phenotypes, particularly in the paediatric setting and consider co-existing mutations that may act as genetic modifiers. We also discuss four newly identified genes associated with skeletal muscle channelopathies.
Expert Opinion/Commentary: Next generation sequencing using gene panels has improved diagnostic rates, identified new mutations and discovered patients with co-existing pathogenic mutations (“double trouble”). This field has previously focussed on single genes, but we are now beginning to understand interactions between co-existing mutations, genetic modifiers and their role in pathomechanisms. New genetic observations in paediatric presentations of channelopathies broadens our understanding of the conditions. Genetic and mechanistic advances have increased potential to develop treatments
