I've run into a very similar problem in the past, luckily it was an easy fix and I didn't brick an ESC before I fixed it.
Sometimes updating firmware it wouldn't chime afterwards [this happened back with v198 the most], and the RS would act very strange, I had to reflash several times to get everything back to being happy.
I traced it down to the USB cable not fully seated into the hotwire. The bottom part of the hotwire case is too tall, and you can get a very slight comm error if the cable isn't in all the way. I trimmed away part of the case with an xacto blade so the USB cable seats in fully with a very slight "click" feel, without putting pressure on the USB cable end.
Haven't had a single issue since I trimmed the case with updating firmware or getting settings to "hold".
Might be worth a look.