Variable number of tandem repeat polymorphisms (VNTRs) in the ACAN gene associated with pectus excavatum.

To the Editor : Pectus excavatum is the most common chest wall deformity, affecting 1 in 400 live births in the United States (1). It occurs commonly in Caucasian males, and is characterized by a depression of the anterior chest wall and sternum resulting in compromised cardiac and respiratory function (2, 3). Genetic factors appear to play a part (4, 5). The CS1 domain of the aggrecan (ACAN) gene exhibits length polymorphisms due to a variable number tandem repeat (VNTR). Each repeat acts as an attachment site for chondroitin sulfate. We hypothesized that costal cartilage in patients with pectus excavatum will show variation in VNTRs outside of the normal reported range of 26–28 (6, 7) that result in a concomitant change in chondroitin sulfate anchorage sites and compromised structural characteristics. The objectives of this study were to determine the prevalence of ACAN VNTRs in pectus excavatum, correlate to severity of disorder, identify subgroups in our patient population, and relate VNTR polymorphisms to subgroup. This is the largest study to date examining specific molecular contributions of a candidate gene to pectus excavatum.