Genetic investigations in neuromuscular diseases

Genetic investigations play an important role in the diagnosis of suspected neuromuscular disease. Establishing a genetic diagnosis provides information regarding prognosis and risks to other family members and allows advice to be given in relation to reproductive options. Moreover, genetic testing increasingly allows for the possibility of targeted treatments and the potential for inclusion in clinical trials. The “genomic revolution” has led to genetic investigations increasingly becoming a first-line investigation in the diagnosis of neuromuscular disease. Historically, a muscle biopsy was often performed early in the diagnostic pathway, and results of muscle histology and biochemical analyses would then guide genetic testing, which was typically limited to testing for common pathogenic variants or sequencing of individual genes known to be involved in the suspected conditions. The development of next-generation sequencing (NGS) and other technological advances has enabled timely and cost-effective genetic testing of blood DNA with a high diagnostic yield (Herman et al., 2021). Therefore, muscle biopsy may now only be necessary in more limited circumstances, such as when genetic testing has not led to a diagnosis or when genetic testing has detected variants of uncertain clinical significance.