That board is double-sided: the CPU and the SSD slot are on the back, while this ITX board has all the connectors and the processor on the top. That makes a difference both for the complexity and cost of building the board, and the complexity of assembling a system with the board, heatsinks and all.

I don't think they were saying that it has to be that big to fit an M.2 drive on it, they're pointing out that in the picture you shared, that space is for the M.2 NVMe drive to be mounted in

But there aren't really generic Pico-ITX cases are there? What's the point of designing a Pico-ITX board if you need a custom case anyways? Just use the Radxa Rock 5B at that point.