Clinical Utility and Diagnostic Yield of Genetic Testing for Inherited Neuromuscular Disorders in a Single, Large...

Most published studies on the clinical utility of genetic testing for neuromuscular diseases (NMDs) focus on disease-specific cohorts and/or involve multiple centers. The aim of this study was to examine the clinical utility and diagnostic yield of genetic testing at a single, large neuromuscular center. Unlike previous studies, this study is unique in that it includes a broad array of patients at a single, large neuromuscular center, providing real-world data that may assist both neuromuscular specialists as well as general neurologists in decision-making regarding the need for genetic testing in patients with suspected NMDs.

Genetic testing results were reviewed for all patients who underwent testing through a single genetic testing company for NMDs in this single laboratory at a large neuromuscular center from 2015 to 2020. Retrospective chart reviews were performed to determine whether genetic testing results conferred a specific NMD diagnosis, including cases where a variant of uncertain significance (VUS) was identified.

Genetic testing was pursued for 192 patients. A positive result, defined as a pathogenic mutation, a VUS, or both, was found in 77.1%. A definitive diagnosis was conferred in 35.9%. The most common testing indication was suspected neuropathy (53.3%), and the indication with the highest diagnostic yield was suspected myopathy (48.7%).

This study provides further evidence of the clinical utility of genetic testing for NMDs in a real-world setting with over one-third of patients tested receiving a definitive diagnosis. Over time, genetic testing will continue to become increasingly accessible, cost-effective, and sensitive, which will lead to even more utilization.