MYOT-related myofibrillar myopathy presenting with normal creatine kinase and electromyography: importance of early genetic testing

A man in his 60s presented with progressive, symmetric weakness of the shoulder and thigh girdles despite normal creatine kinase and electromyography findings. Lumbar spine MRI revealed only age-appropriate degenerative changes, insufficient to explain his symptoms. A targeted 60-gene next-generation sequencing panel identified a heterozygous MYOT c.179C>T (p.Ser60Phe) variant, confirming MYOT-related myofibrillar myopathy. Cardiac evaluation demonstrated mild aortic-root dilatation, mitral regurgitation and frequent premature atrial contractions. The patient underwent supervised eccentric-strengthening physiotherapy with stable function over 1 year. This case underscores that MYOT myopathy can present with preserved enzyme levels and normal electrodiagnostic studies, risking diagnostic delay if clinicians rely solely on conventional testing. Early gene-panel sequencing in patients with unexplained proximal weakness can expedite diagnosis, guide cardiac surveillance and inform family cascade testing.