Few things in the way:
1) On a general perspective, marketing a disabled character in a videogame, a medium primarily known for action and violence as a primary element, would be extremely difficult. While alternate perspectives and opinions do exist, on the whole, I don't think most people want to play as characters with disabilities. It just doesn't fit into the traditional hero archetype, and these days publishers want to be as safe as possible.
2) It'd be really difficult to create a character that isn't a token minority, or who doesn't exist to embody the entire spectrum of "disabled persons". Furthermore, you risk alienating certain pitchfork-carrying, Bible-reading demographics by including too much variety in your cast to help represent multiple perspectives, and you don't want to bloat that cast too much in doing so. Fact is, you want disability to define characters, but not to the point where that is all they are, a disability.
3) The actual gameplay representation is a big problem, too. On the one hand, you can include perks in an RPG that make you less intelligent, or go based on stats, etc., but how do you do that in a way that isn't portrayed completely as a disadvantage? How do you manage positive representations when mechanically, a given character is inferior on an objective level? If you give bonuses to disabled characters, how do you do so in a way that feels natural within that game, without trivialising that disability? Those are hard questions to answer and I'm not sure there are ideal ways to go about it.
I'd say that, within an RPG, the best way to handle disability is to look at it in terms of basic stats. While you won't say a character with an intelligence of 3 has X mental issues, you can certainly infer that he/she isn't the sharpest tool in the shed. Meanwhile, a character with low vitality can be taken as sickly and frail... low agility can be understood as clumsiness and perhaps a handicap of some sort, like an injured leg... low perception is colour blindness, etc.
If you think of a stat at 5/10 as being "average", then when you start to hit 1-2 on that scale, disability is one of the best explanations, while for higher levels it allows players to role-play a genius, a sharpshooter, etc. The beauty of such a system is that it forces compromise and effectively says "there are no perfect people, everyone has problems of some sort." While you could get away from it by avoiding min/maxing, that would just leave you with a generic everyman, with all the strengths and weaknesses that entails.
The hard part of a system like that though, is having the game world respond properly. Fallout managed to do so decently, but aside from the "retard" dialogue, it was rare that the game actually gave you special treatment for low stats. Characters with low perception didn't miss plot-critical events or items, low agility didn't impair your movement speed outside of combat, etc. Coming up with good ways for the game to reinforce player choices is definitely a challenge, but it's less an issue of actually knowing how to do it and more an issue of just doing it well, and being able to create so much content. I think simple things like the various stat descriptions in Divinity II go a long way. "Your twig-like arms were a subject of mockery during your youth, and adulthood hasn't seen much improvement. You struggle to perform even basic tasks requiring physical strength, much less those requiring any more than modest exertion." says a lot more about your character's ability and disability in a few lines of text, than all the fancy character models in the world can.
The real downside to this sort of approach is that you can't get as specific about disability... you have to do that through building strong characters within a larger narrative, not generalised descriptions. Perks might be able to help add detail and flesh things out, but ultimately it's unrealistic to expect developers to add dozens of diseases, disabilities, disorders, etc. into their game and then be able to account for them all. However, I think the generalised approach works precisely because players are able to fill in the blanks and decide for themselves. Give the player a few flavour dialogue options to explain why he/she walks with a limp, and instantly you go a long way towards making the player feel involved in the world, and like that disability is more than just a statistic, even if there's no 100% direct response by the game.
As far as specific characters go... well, turning the disability into a character trait (i.e. missing an eye = badass pirate eyepatch, missing legs = bionic legs) is a good way to include disability without making those characters feel like they're dragging down everyone else. Sometimes a sub-plot related to disease, mental illness etc. can fit into a game, though it's rare to see so outside of supporting roles (probably because people don't want to play a protagonist with dementia or something). Another option is to simply design a game around the fact that disability isn't going to drastically hurt gameplay... including paraplegics? Be sure there's a strong dialogue system and social element to the game. Mental illness? Include a level where a character has to confront inner demons, or turn it into gameplay - I think I've seen at least a few JRPGs do this to some success. Finding the right balance and tone to address disability is still going to be hard, of course, but so long as your inclusion isn't offensive or pandering, I think it's good to simply have that inclusion even if it's not perfect. Flawed characters are always more interesting, anyway.
