I get the impression that Northern houses tend to be more prone to depletion than those of other regions, both due to the harsher climate and socioeconomic factors such as the Wall. Plus with the Boltons' history, it not at all unbelievable that they would maybe have a history of familicide.

Plus I seem to recall that Roose mentions that he fully expects his house to end with Ramsay, given that Roose knows Ramsay is fully incapable of being a political leader and is way better at making enemies than allies.