What's / What is your problem?
What's / What is the matter (with smb. / smth.)?
What's / What has happened (to smb. / smth.)?
What's / What is wrong (with smb. / smth.)?
What is it? (реакция на что-то неожиданное и непонятное: шум / шорох /голос / ...)
What's / What is the trouble (with smb.)? Why? (после ответа на неожиданный вопрос):