Okay, I tried and managed to (kind of) reproduce the issue. It didn't happen automatically for me, probably because I don't have a 4K monitor.
Could you try toggling these 3 options? In particular, the "Automatically Scale User Interface" option might solve the issue.

I only tried it in Gamemode, not in Big Picture mode. Let me know if I should have tried the other one instead.
EDIT: ah... my apologies I checked your other reply again and realized that you had already tried toggling the "Automatically Scale User Interface" option... I'm afraid I'm out of ideas, if I leave that option on I cannot reproduce this issue on my hardware.