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

Abstract

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 (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) were lower in adults with WS (p p 1/FVC ratio was more frequently below the lower limit of normal in cases (p p p Eln+/− mice, ex vivo lung volumes were increased (p 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.

Keywords

• Williams Beuren syndrome
• pulmonary function tests
• air trapping
• obstructive pulmonary disease