Airflow Obstruction in Adults with Williams Syndrome and Mice with Elastin Insufficiency.

Williams-Beuren syndrome (WS) results from the deletion of 25-27 coding genes, including elastin ( ELN ), on human chromosome 7q11.23. Elastin provides recoil to tissues; emphysema and chronic obstructive pulmonary disease have been linked to its destruction. Consequently, we hypothesized that elastin insufficiency would predispose to obstructive features. Twenty-two adults with WS (aged 18-55) and controls underwent pulmonary function testing, 6 min walk, and chest computed tomography (CT). Lung and airspace dimensions were assessed in Eln +/- and control mice via microCT and histology. The forced expiratory volume in 1 s (FEV 1 ) and the ratio of FEV 1 to forced vital capacity (FVC) were lower in adults with WS ( p < 0.0001 and p < 0.05, respectively). The FEV 1 /FVC ratio was more frequently below the lower limit of normal in cases ( p < 0.01). The ratio of residual volume to total lung capacity (RV/TLC, percent predicted) was higher in cases ( p < 0.01), suggesting air trapping. People with WS showed reduced exercise capacity ( p < 0.0001). In Eln +/- mice, ex vivo lung volumes were increased ( p < 0.0001), with larger airspaces ( p < 0.001). Together these data show that elastin insufficiency impacts lung physiology in the form of increased air trapping and obstruction, suggesting a role for lung function monitoring in adults with WS.