Mario is Missing! is very famous for its sprite for Luigi (although most people refer to him in this game as "Weegee"). Weegee is still used in video-game related jokes today. You can only see Weegee in the DOS version of the game.
Mario is Missing! was originally developped for PC as a point and click edutainment adventure, similar to Carmen Santiago Games , however the SNES does not lend itself well to that type of gameplay, so instead runs on the Super Mario World engine and allows similiar action.