Prevent multiple registrations from the same email using + character
Check email before register user with add your custom validator in hook_form_alter, then check user email without +secondpart :

As a Example you can Try something like this (I didn't test this but it can give you a good clue to achieve what you want ) 

 function YOURMODULENAME_form_alter(&amp;$form, &amp;$form_state, $form_id){
       if ($form_id == "user_register_form") {
            // add your custom validator
            $form['#validate'][] = 'my_custom_email_validate';
       }
     }


in your custom validator check it with regular expression

function my_custom_email_validate($form, $form_state, $form_id){
    // dpm($form_state['values']);
    $mail = $form_state['values']['mail'];
    preg_match_all('/(.*)\+.*(@.*)/',$mail,$matches);
if($matches){
    // this mean it has  xxx+xx@xxx pattern
    $clean_mail = $matches[1][0].$matches[2][0];
    $user_load = user_load_by_mail($clean_mail);
    if($user_load){
        form_set_error('mail',t('Sorry,This email used before.don\'t waste your time dear spammer'));
        return false;
 }
}