I've been playing League of Legends consistently for over two years now; I have two pentakills. For those unfamiliar, a pentakill is awarded when one person lands the killing blow on every enemy of the opposite team in a short amount of time. It's extremely rare and very difficult to do. One gamer, who goes by the name TheAieron in League of Legends, managed to accomplish this feat without the use of his hands.
Keith Knight, who goes by Aieron in-game and on his Twitch.tv account, was born with Amyoplasia Arthrogrypos — meaning, he was born with less muscle mass in his body and his joints have stiffened as he's aged. As a result, he has very little movement in his arms, legs, and hands. Yet he still manages to play League of Legends without a hitch — as evidenced by his recorded pentakill.
Keith plays LoL using a custom setup: he uses the mouse with his left hand, while his Q,W,E, and R abilities are synched with external switches that he controls with his elbow and feet. His favorite champion is Lee Sin, certainly not an easy champ to play.