| Summary: | Williams–Beuren syndrome (WS) results from the deletion of 25–27 coding genes, including elastin (<i>ELN</i>), 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 <i>Eln<sup>+/−</sup></i> and control mice via microCT and histology. The forced expiratory volume in 1 s (FEV<sub>1</sub>) and the ratio of FEV<sub>1</sub> to forced vital capacity (FVC) were lower in adults with WS (<i>p</i> < 0.0001 and <i>p</i> < 0.05, respectively). The FEV<sub>1</sub>/FVC ratio was more frequently below the lower limit of normal in cases (<i>p</i> < 0.01). The ratio of residual volume to total lung capacity (RV/TLC, percent predicted) was higher in cases (<i>p</i> < 0.01), suggesting air trapping. People with WS showed reduced exercise capacity (<i>p</i> < 0.0001). In <i>Eln<sup>+/−</sup></i> mice, ex vivo lung volumes were increased (<i>p</i> < 0.0001), with larger airspaces (<i>p</i> < 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.
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