A new diagnosis of Williams-Beuren syndrome in a 49-year-old man with severe bullous emphysema

Abstract

Williams-Beuren syndrome (WBS) is a chromosomal microdeletion syndrome typically presenting with intellectual disability, a unique personality, a characteristic facial appearance, and cardiovascular disease. Several clinical features of WBS are thought to be due to haploinsufficiency of elastin (ELN), as the ELN locus is included within the WBS critical region at 7q11.23. Emphysema, a disease attributed to destruction of pulmonary elastic fibers, has been reported in patients without WBS who have pathogenic variants in ELN but only once (in one patient) in WBS. Here we report a second adult WBS patient with emphysema where the diagnosis of WBS was established subsequent to the discovery of severe bullous emphysema. Haploinsufficiency of ELN likely contributed to this pulmonary manifestation of WBS. This case emphasizes the contribution of rare genetic variation in cases of severe emphysema and provides further evidence that emphysema should be considered in patients with WBS who have respiratory symptoms, as it may be under-recognized in this patient population.

Keywords: Williams-Beuren syndrome; elastin; emphysema; intellectual disability.

Figure 1

Bullous emphysema in WBS: a) Coronal section of the anterior thorax from reconstructions of a non-contrast chest CT obtained on initial presentation demonstrating bilateral, asymmetric lower lobe emphysematous bullae. b, c) 3 dimensional volume rendered images from repeat CT imaging several months later confirm a large left bulla (blue projection in panel b) extending across the midline into the right hemithorax, as well as causing distortion of vascular structures in the left lung (denoted by the sparse vascularity in panel c). d) SNP Array Result. The common, typical 1.5 Mb deletion in WBS is seen on chromosome 7, encompassing the WBS critical region.

Figure 1

Bullous emphysema in WBS: a) Coronal section of the anterior thorax from reconstructions of a non-contrast chest CT obtained on initial presentation demonstrating bilateral, asymmetric lower lobe emphysematous bullae. b, c) 3 dimensional volume rendered images from repeat CT imaging several months later confirm a large left bulla (blue projection in panel b) extending across the midline into the right hemithorax, as well as causing distortion of vascular structures in the left lung (denoted by the sparse vascularity in panel c). d) SNP Array Result. The common, typical 1.5 Mb deletion in WBS is seen on chromosome 7, encompassing the WBS critical region.

Figure 2

Patient photos from childhood (a) and present day (b) demonstrate classic facial features of WBS including a short, up-turned nose, full cheeks, and a delicate chin in childhood, early greying in adulthood, full lips, and a bulbous nasal tip. a) Childhood photographs obtained with permission from the patient’s family. b) Present day photographs by Rick Guidotti of Positive Exposure, published with permission from the photographer and patient. Patient now uses continuous supplemental oxygen to maintain blood oxygen saturation levels about 88%. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1552-4833