Apologies if this has been mooted before, but something that occurred to me recently is Victoria Winters Clark.
She [spoiler]married a man that doesn't exist and then she herself vanished into thin air.[/spoiler] Now I understand that any investigation of her disappearance wouldn't begin 30 odd years later, but when you think about some, someone would have missed her (Mrs. Hopewell, her friends/coworkers at the foundling home, maybe some of the children she was close to). Also, after a few years of not paying income tax, the IRS would certainly want to know where she was. The of course there would be the people of Collinsport, the minister who married her and Jeff, blood tests and marriage licenses, people who even just knew her as the Collins boy's governess.
Perhaps a storyline in a new DS could deal with that in some way, perhaps a child at the foundling home remembered her and years later is trying to find out what happened to her.