When a person's face is so bloated and deformed that it's impossible to distinguish it from their ass. As it is, the ass already resembles a hippopotamus face. For the poor bastard sporting one of these, it also resembles theirs. It is a synonym with "Ed Zachary Disease".
Ryan: When I got home I found out that girl from the bar last night, was a major hippotwatamus
Jeff: Oh yeah, I went on spring break with her and wasn't sure if she had a penis or not.