The incidence of a solitary maxillary median central incisor (SMMCI) tooth in the general population is low, in either the primary or secondary dentition. The most common cause of a missing maxillary central incisor is trauma, or more rarely hypodontia. However, SMMCI is also a recognized genetic anomaly and affected individuals can be carriers for a potentially more serious condition affecting midline development of the brain and face, holoprosencephaly (HPE). The presence of an SMMCI of unknown aetiology is therefore considered a risk factor for HPE, even in the absence of any other clinical signs. The orthodontist may be responsible for diagnosing cases of SMMCI with no obvious cause, and in these subjects due consideration should be given to referral for the appropriate genetic testing and counselling.