A case of Oculo-Auriculo-Vertebral (OAV) spectrum in a mother and probable VATER association in her daughter: coincidence or connected?
We present a case of a 37 yr old lady with an epibulbar dermoid cyst and eyelid coloboma, previously removed preauricular skin tags, and facial asymmetry – features that fit within the Oculo-Auriculo-Veretebral (OAV) spectrum. Her 6 yr old daughter was diagnosed as a neonate with probable VATER association, following the findings of oesophageal atresia, tracheo-oesophageal fistula, and hemivertebrae at the upper thoracic level.
Both OAV and VATER are of uncertain aetiology and thought to be separate sporadic conditions. Both conditions, however, involve structures derived embryonically from the axial mesoderm. The finding of abnormalities within axial mesodermal structures in both parent and child, raises the notion that disruption of an underlying gene involved in axial mesodermal development may connect the pair.
A candidate gene considered in this case is Axis Inhibitor 1 (AXIN1). The gene, better known for its role in hepatocellular carcinoma, is thought to be involved in the WNT signaling pathway. This pathway plays an important role in directing cell differentiation, polarity and growth – particularly at the level of the axial mesoderm. Disruption of axin in animal models causes abnormalities of axis formation.
A mutation within the coding region of AXIN1, or an epimutation disrupting expression of the gene, are proposed as possible explanations for a connection between mother and daughter. Results of AXIN1 sequencing and methylation studies of the AXIN1 promoter region on DNA from both patients will be presented.