Review of the etiologic heterogeneity of the oculo-auriculo-vertebral spectrum (Hemifacial Microsomia)

Hemifacial microsomia is a congenital asymmetry of the lower face that may be associated with other cranial and extracranial anomalies. The variability of its severity, and wide range of anomalies that have been reported with it in some cases has resulted in these composite manifestations being given a number of names, including oculo-auriculo-vertebral spectrum (OAVS). Etiology is often stated to be a perturbation of embryonic blood flow in the developing region, although other factors may also play a role in some cases. Depending on what is considered to be minimum criteria for affected classification, what is often to be presumed to be a sporadic event in a family may be the more severe manifestation of a familial condition. Etiological factors are clearly heterogeneous, the investigation of which is confounded by not only the lack of a refined affected phenotype, but also the apparent influence of genetic factors in some instances that directly influence phenotype perhaps through alteration of mesodermal development, or indirectly through increased susceptibility to vascular disruption. Future studies likely to advance knowledge in this area will need to incorporate an analysis of who may be minimally affected in families, so that advances in genotyping will have greater power to distinguish genetic factors that may influence OVAS through interaction with environmental factors in particular families. The same genetic-environmental factors and or etiological mechanisms may then be investigated in apparently sporadic cases.