It's unclear whether you are saying this stuff definitely worked with the 486DX-33 or not.

If it did, then you might consider that this looks like an early 486 board and the BIOS may not know about the DX2-66 and thinks you have a 50 MHz bus, and the ISA slots are running at some unusual speed. If so you might look for the ability to disable any Auto Config features any manually set the ISA divider to 4. You may need to use AMISETUP if the options to do so have been hidden.

Did it properly work with a DX33 ?? The retro web page says it can use a DX2: https://theretroweb.com/motherboards/s/informtech-it486sr.
What joystick are you using ? Sounds like something has gone a-miss and is getting worse. check the PSU, all rails. Also look the caps on the board over closely.

The motherboard's manual does list "66MHz 486DX2" as a supported (max) CPU. Jumper settings (CPU type & oscillator frequency) and cache speed requirements are the same than for a 33MHz 486DX CPU.

Joysticks have worked fine with the 486DX@33MHz. The GM/SoundCanvas MIDI (in Doom/Duke3D) situation is unknown as have not tested with the 486DX@33MHz (have sold that CPU after the upgrade). The PC is one of my original ones from the early 90s and I didn't own any Roland/GM/SoundCanvas gear back then.

I'll try to investigate if the BIOS (bus) speed adjustment has any impact on this. And in the meanwhile I'll try to get a 486DX-33 SX419 CPU to rule out any issues with the MIDI adapter (the SCC-1 card).

-TamaMan

Update: Changing the DX2 recommended (and BIOS default) "AT Bus Clock Selection" BIOS setting from "CLKI/4" to "CLKI/6" seems to fix the GM/Sound Canvas MIDI issue in Doom and Duke Nukem 3D. Need to test the joystick still.

Update 2: The joystick issue was non-related and was limited to only couple of game adapters. Game ports on a Sound Blaster 2.0 and the IT Multipack-4 work OK.

I'll try to measure the bus speed to document the difference between BIOS settings "CLKI/4" and "CLKI/6" if someone else was similar issues with an MPU/SCC-1 card.