David Cameron was forced to issue an apology after comparing Commons heckling by Ed Balls to "like having someone with Tourette's sitting opposite you".
The Prime Minister directed the jibe at the shadow chancellor in an interview with the Sunday Telegraph, but faced an immediate backlash for citing the inherited neurological condition.
Downing Street said the remark was made "off the cuff".
But a spokeswoman added: "The Prime Minister would not have meant to offend anyone. He apologises if any offence has been caused."
"He just annoys me," Mr Cameron said in the interview of Mr Balls - whose gestures and comments aimed at the premier have become a well-known feature of his weekly question time session.
"But I'm very bad, in the House of Commons, at not getting distracted, and the endless, ceaseless banter, it's like having someone with Tourette's permanently sitting opposite you."
Labour MP Ian Lucas said it was a "very nasty and ignorant comment" and campaigners called on people to sign a petition complaining at Tourette Syndrome being the butt of jokes.
The petition, set up before Mr Cameron made his comment, complains that the term "Tourette's" is often used humorously to describe any apparent inability to control sounds and movements.
That displays "a total lack of understanding of a condition which is debilitating, socially excluding and at times extremely painful", it says.
And it expresses an ambition to garner enough support to petition Mr Cameron's government "to protect people living with Tourette Syndrome to the degree they deserve".