Ryanodine Receptor 1-related myopathies (RYR1-RM) comprise a spectrum of disorders caused by pathogenic variants in the RYR1 gene and are the most common of the non-dystrophic congenital neuromuscular diseases (NMD) in the United States. Electrical impedance myography (EIM)—a noninvasive and objective measure of muscle health—has been evaluated in other NMD populations and has been shown to quantify disease progression. Limited longitudinal data and disease progression models exist for RYR1-RM. These exploratory analyses sought to (1) investigate EIM outcomes over a 6-month natural history period in symptomatic, ambulatory participants with confirmatory RYR1 genetic testing, (2) compare EIM outcomes to those from previously reported healthy controls, and (3) correlate EIM outcomes with the Motor Function Measure-32 (MFM32). EIM and MFM32 were administered at baseline and 6 months to 24 participants (NCT02362425): 11 children (46%) and 13 adults (54%). No difference was observed in EIM between baseline and 6 months in the RYR1-RM cohort, which is consistent with previous evidence of slow disease progression. While not statistically significant, the phase value, a calculation derived from EIM-measured muscle reactance and resistance, of the RYR1-RM cohort (mean (95% CL) = 7.7 (5.8, 9.7), 6.4 (4.9, 7.8) in children, adults, respectively) trended lower than that of healthy controls (mean (95% CL) = 10.1 (2.3, 17.9), 8.4 (0.2, 16.5) in children, adults, respectively), suggesting pathology. A correlation was found between the MFM32 Domain 1 (standing/transfers) and the lower extremity EIM phase average (ρ = 0.58, p = 0.003) and between the MFM32 total score and the 8-muscle EIM phase average (ρ = 0.426, p = 0.038). These correlations are consistent with proximal muscle weakness, the most common clinical manifestation in RYR1-RM. Additional studies are needed to propose the use of EIM as a potential biomarker. Funding provided by NINR, NINDS and Clinical Center intramural funds.