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Keegan is awaiting the results of a scan on Howey's foot but he fears it could be a stress fracture, meaning another substantial lay-off.
"The two players have no chance for this week's derby," he said.
"Sylvain has pulled his hamstring so we are looking at four to five weeks.
"The last time Steve Howey had something similar to this he was sidelined for four weeks.
"We have to look on it as an opportunity for someone else, that is all we can do.
"We do have a lot of centre-backs in the club so if there is one position where we can take a couple of knocks it is probably there more than anywhere else," Keegan told the club's official website.
WIGAN MATCH REPORT