An evaluation of clinical presentation and genetic testing approaches for patients with neuromuscular disorders

Inherited neuromuscular disorders (NMDs) are a large group of genetic conditions characterized by impaired peripheral nerve, motor neuron, neuromuscular junction, or skeletal muscle function. These conditions are also known to have clinical and genetic heterogeneity and variable ages of onset. Clinical evaluation for NMDs has increasingly incorporated molecular genetics. However, genetic testing is complicated by the variety of testing options and the ambiguity of NMD phenotypes. Examining test selection and yield may elucidate testing recommendations and improve the diagnostic journey for these patients. This retrospective chart review evaluated the clinical presentations, genetic testing approaches, and diagnostic outcomes of 155 patients with suspected NMDs at Cincinnati Children's Hospital Medical Center. A total of 262 individual tests were ordered, averaging 1.7 tests per patient. The clinic utilized 26 separate genetic tests, with test yields ranging from 0% to 66%. Overall, 21% of patients received a genetic diagnosis. Of all the clinical findings evaluated, elevated CPK levels with or without muscle weakness were the most informative symptoms correlated with a diagnostic result. This study highlights several genetic testing considerations for NMDs, including the variability of diagnostic outcomes. This knowledge is relevant to clinicians and patients, especially during the pretest counseling and consenting process.