User blog comment:Masseffect7/Mass Effect 4 - No Connection to Shepard/@comment-1786741-20131020213539/@comment-1679409-20131020220808

I think it's easier than you think. With Synthesis, one of the biggest issues would be green eyes and veins (and green lights for synthetics). This can be worked around by often having characters in armor and helmets. Not to mention, in the grand scheme of things, it's probably not too hard to change eyes and lights to green and add green veins, no harder than it we would be to add new outfights for characters. It's just some editing and recoloring on an existing skin.

And like Mike Gilbert said, refusal could obviously be treated as non-canon. I will say, it would be cool if they decided to do an alternate universe where Shepard did go with refusal and we get to play in the next cycle.