F31. Longitudinal neurophysiological study of dominant intermediate Charcot-Marie-Tooth type C neuropathy

Introduction Dominant intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) is associated with mutations in the YARS gene, encoding tyrosyl-tRNA synthetase (TyrRS). In a prospectively designed study we were the first to report the phenotype and genotype of DI-CMTC from a U.S. and a Bulgarian family using electrodiagnostic (EDX) and morphological studies. Here we present longitudinal data for the U.S. family 16 years after the initial evaluation. Methods After re-consenting, 13 of 21 original DI-CMTC participants underwent EDX and physical examinations. Data of 2000 and 2016 were compared for specific nerves using paired t-tests. General linear model univariate analysis was used to relate findings to patient age. Data are presented as mean ± SD. Results Four women and 9 men were examined at ages 8–77 years in 2000 and 24–93 years in 2016. During this time median nerve compound muscle action potential (CMAP) amplitudes decreased from 9.3 ± 2.9 mV to 6.0 ± 2.9 mV (p = 0.002), while distal motor latencies (DML) increased from 4.2 ± 0.6 ms to 4.5 ± 0.6 ms (p = 0.04); mean motor nerve conduction velocity (MNCV) remained largely unchanged at 37 m/s. Over the same period ulnar nerve CMAP amplitudes decreased from 9.2 ± 2.1 mV to 6.1 ± 1.8 mV (p = 0.004); mean MNCV remained the same at 39 m/s. In 2000 and 2016 all adult participants had absent peroneal motor responses, as well as absent tibial responses (except for 2 patients with CMAP amplitudes 1 mV and MNCV 32–35 m/s in 2000 and 28–32 m/s in 2016). In the interval sural sensory nerve action potential (SNAP) amplitudes changed from 2.0 ± 2.5 mV to 1.0 ± 2.4 mV (p = 0.10), and sensory nerve conduction velocities (SNCV) from 39.3 ± 1.0 to 35.5 ± 2.1 m/s (p = 0.13); this did not reach statistical significance. Median nerve sensory peak latencies increased from 3.4 ± 0.4 to 3.9 ± 0.4 ms (p = 0.01), SNAP amplitudes changed from 7.2 ± 5.3 to 6.5 ± 5.1 mV (p = 0.055), and SNCV from 46 ± 1.7 to 41.3 ± 7.6 m/s (p = 0.328). There was an age-dependent decrease of CMAP amplitudes of median (p = 0.044), peroneal and tibial (p  Conclusion In this study MNCV remained stable over 16 years, but motor and sensory amplitudes decreased. DI-CMT C appears to produce a progressive age- and nerve length-dependent axonal degenerative process. Longitudinal EDX findings are consistent with our previous cross-sectional morphological study of sural nerves, which also revealed an age-dependent loss of large and small myelinated axons.