Minor physical anomalies: Potentially informative vestiges of fetal developmental disruptions in schizophrenia

Minor physical anomalies (MPAs) are subtle signs of developmental deviation that are observed at an elevated frequency among patients with schizophrenia. These minor morphological abnormalities of the craniofacial region and limbs arise during fetal development and represent a set of risk markers for schizophrenia. Although MPAs are not specific to schizophrenia, established findings about MPAs vis-à-vis schizophrenia include the replicated findings that MPAs are more prevalent among individuals with schizophrenia than healthy controls, MPAs are more prevalent among individuals with schizophrenia than unaffected relatives, and MPAs are not consistently associated with symptom domains or other risk markers, such as neurological soft signs. Unresolved questions include whether or not MPAs are more prevalent among unaffected relatives than healthy controls, and which specific MPAs are most associated with schizophrenia. This overview presents three promising avenues of further research on MPAs, including: (1) studies relying on traditional summary scores that combine multiple MPAs, which may have a role in prospective risk stratification in conjunction with other risk markers and endophenotypes; (2) research on specific, quantitatively assessed MPAs (especially in specific craniofacial structures) that may inform neurodevelopmental understandings of schizophrenia; and (3) genetic studies aimed at identifying the heritable and nonheritable determinants of specific MPAs, which may increase the field's understanding of the origins of MPAs and the nature of their association with schizophrenia.