Electrophysiological Characterization of a MYH7 Variant with Tremor Phenotype

BackgroundThe concept of a myopathy with associated tremor (myogenic tremor) in humans has been previously described for specific MYBPC1 (Myosin-Binding Protein C) variants. Here we report for the first time an individual with tremor who was found to have a de-novo likely pathogenic variant in Myosin Heavy Chain 7 (MYH7). We provide a detailed electrophysiological characterization of the tremor syndrome in a human individual with a myopathy and this pathogenic MYH7 variant to provide further insight in the phenotypic spectrum and pathomechanism of myogenic tremors in skeletal sarcomeric myopathies. MethodsElectromyographic recordings were obtained from facial muscles, as well as bilateral upper and lower extremities. Results10 to 11 Hz activity was observed in the face and extremities during recordings with muscle activation. There were intermittent episodes of significant left-right coherence that would modulate across muscle groups throughout the recording, but no coherence between muscles at different levels of the neuraxis. ConclusionsA possible explanation for this phenomenon is that the tremor originates at the sarcomere level within muscles, which is then picked up by muscle spindles and leads to activating input to the neuraxis segment. At the same time, the stability of the tremor frequency does suggest the presence of central oscillators at the segmental level. Thus, further studies will be needed to determine the origin of myogenic tremor and to better understand the pathomechanism.

Automated summary

This study reports the first case of an individual with tremor found to have a de-novo likely pathogenic variant in Myosin Heavy Chain 7 (MYH7) gene. Through a detailed electrophysiological characterization of the tremor syndrome in this individual with a myopathy and MYH7 variant, the phenotypic spectrum and pathomechanism of myogenic tremors in skeletal sarcomeric myopathies are further elucidated. The results suggest that the tremor may originate at the sarcomere level within muscles and is picked up by muscle spindles, leading to activating input to the neuraxis segment. Additionally, the stability of the tremor frequency indicates the presence of central oscillators at the segmental level.