(warning: this has spoilers, do not read if you have not completed the story line) It is a glitch. This glitch is hard to explain so try to bare with me. After the fight against Logan's elite troops in Bowerstone old quarter, my wife and kids had disappeared. I had no idea why, I assumed they had just died since they were living in Old Quarter during the battle; I then remarried a different woman. After the fight against The Crawler in Bowerstone Market, my new wife and kids disappeared as well and they were currently living in Bowerstone Market. I assumed this happened because they died during the battle like my last family, but they didn't. That's when I noticed the pattern; whenever a major battle goes on in the region that your wife is living in, 90% of the time she will disappear afterwards. and I found out that it's just a common glitch in the game. Fortunately, there are ways to avoid it. 1.) waiting to marry until the story line is over. 2.) avoid moving your family into Bowerstone Old Quarter, Bowerstone Market, and the castle, this is until the story line ends. The safest regions I have found to move my family into and avoid the missing wife glitch is Millfields and Brightwall.
I hope this helped a bit.
I have completed the game three times already.
My xbox gamertag is: deviltothemetal