what's the matter?; what's wrong?
what happened (to) ...?; what have you done (with) ...?; where is ...?
どうしたの、顔色が悪いよ。
What is wrong? You look pale.
どうしたの、泣いているのか。
What is the matter? Are you crying?
どうしたの、急に黙って。
What happened? You suddenly went quiet.