Purpose: This study describes the performance on a perspective- and role-taking task in 27 children, ages 6-13years, with 22q11.2 deletion syndrome (22q11.2DS). A cross-cultural design comparing Dutch- and English-speaking children with 22q11.2DS explored the possibility of cultural differences. Method: Chronologically age-matched and younger typically developing (TD) children matched for receptive vocabulary served as control groups to identify challenges in referential communication. Results: The utterances of children with 22q11.2DS were characterised as short and simple in lexical and grammatical terms. However, from a language use perspective, their utterances were verbose, ambiguous and irrelevant given the pictured scenes. They tended to elaborate on visual details and conveyed off-topic, extraneous information when participating in a barrier-game procedure. Both types of aberrant utterances forced a listener to consistently infer the intended message. Moreover, children with 22q11.2DS demonstrated difficulty selecting correct speech acts in accordance with contextual cues during a role-taking task. Conclusion: Both English- and Dutch-speaking children with 22q11.2DS showed impoverished information transfer and an increased number of elaborations, suggesting a cross-cultural syndrome-specific feature.