Objective and Importance: To report a case of the bilateral transposition of the maxillary canines with the premolars in a 17-year-old female with Down syndrome. Clinical Presentation and Intervention: A 17-year-old female presented with moderate mental retardation; she was short and of small stature, and she had a round cherubic face and a broad forehead. Clinical intraoral examination revealed bilateral malpositions of the maxillary canines and premolars as transposition. She had an open mouth, macroglossia and a protruding tongue. The case required the combined orthodontic and prosthetic treatment to achieve an acceptable morphologic and esthetic occlusion. However, the parents refused to accept the proposed treatment. Extractions of the roots and caries treatment were done as these were considered priority for the patient. Conclusion: This rare and severe positional anomaly represents an orthodontic challenge and its correction involves treatment risk and requires a great deal of control and carefully applied mechanics.

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