I'm sure no expert. But cabin de-pressurization is the same big plane or small. Hypoxia is the same no matter what size plane. Systems are, I'm sure, different. But my bet is on catastrophic depressurization. The cause of which, I have no idea. Causing disorientation and then unconsciousness. Then the plane just flies on until it runs out of fuel.
Or, it could be Aliens. Or it flew into a parallel dimension. Or......