One of the most unique features of distal 18q- is congenital aural atresia (CAA). This occurs when the ear canal is either narrowed or closed off completely. This is a frequent cause of hearing loss in people with a deletion of 18q. Although CAA is associated with other genetic conditions, it almost always occurs in association with anomalies of the outer ear.  In people with 18q-, the outer ear is normal. This is such a unique finding that, when a person has aural atresia and a normal outer ear, there is almost always a chromosome 18q change.

Until recently, we did not know exactly which gene on 18q was responsible for this finding. We had narrowed down the region of the chromosome within which the gene must reside, but we did not know which of the 12 genes in that region was responsible.  However, a paper in 2010 reported several families with isolated CAA. Two had small deletions of 18q, but only one gene was missing in both families: TSHZ1. The authors then identified another family that had a single change at the base pair level which led to CAA. This supported the association between CAA and TSHZ1. This gene is located at 18q22.3. TSHZ1 stands for teashirt zinc finger homeobox 1. It is a transcription factor, which means that it plays a role in controlling the expression of other genes.

In summary, if a person is missing this gene, they are at an increased risk for having CAA. However, not everyone missing this gene will have this anomaly. In one study published by the Research Center, 78% of people that were missing a region involving this gene have CAA. In addition, there have been some more recent papers that link this gene with other birth defects associated with 18q-, such as cleft palate and even vertical talus (a birth defect involving the foot). As time goes on, additional research will determine whether this link is real. However, in the meantime, it is exciting to have a genetic explanation for one of the most unique features of distal 18q-.