Pulmonary function and emphysema in Williams–Beuren syndrome

Abstract

Williams-Beuren Syndrome (WBS) is caused by a submicroscopic deletion on chromosome 7q11.23 that encompasses the entire elastin (ELN) gene. Elastin, a key component of elastic fibers within the lung, is progressively destroyed in emphysema. Defects in the elastin gene have been associated with increased susceptibility towards developing chronic obstructive pulmonary disease (COPD) and emphysema in both humans and mice. We postulate that hemizygosity at the elastin gene locus may increase susceptibility towards the development of COPD and emphysema in subjects with WBS. We describe an adult subject with WBS who was a lifelong non-smoker and was found to have moderate emphysema. We also examined the pulmonary function of a separate cohort of adolescents and young adults with WBS. Although no significant spirometric abnormalities were identified, a significant proportion of subjects reported respiratory symptoms. Thus while significant obstructive disease does not appear to be common in relatively young adults with WBS, subclinical emphysema and lung disease may exist which possibly could worsen with advancing age. Further investigation may elucidate the pathogenesis of non-smoking related emphysema.

Skin findings in Williams syndrome

“…Because of the prevalent morbidity and mortality associated with the vascular disease in this condition, there has been less analysis of the effects of elastin haploinsufficiency on other elastic tissues. Case reports have noted emphysema, bladder, and colonic diverticuli, [Ignacio et al, 2012; Partsch et al, 2005; Sammour et al, 2006; Schulman et al, 1996; Wan et al, 2010] features potentially attributable to elastin insufficiency, and two studies have commented on the skin findings in the condition. Urban et.al.…”

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

“…While the paucity of reports of emphysema in WBS might suggest it as a rare complication of the disorder, the prevalence of lung involvement may be underestimated. For example, a survey of 16 adolescents and young adults with WBS found that 50% endorsed symptoms of shortness of breath, 43.8% reported cough, and 31.3% reported wheezing requiring medical treatment [Wan 2010]. Pulmonary imaging was not available as part of this study and it is possible that mild emphysema was present in some of these subjects.…”

“…There has been only one previously-reported case of emphysema in this syndrome [Wan 2010]. Here, we present a second adult patient with both WBS and emphysema.…”

Williams-Beuren Syndrome and Congenital Lobar Emphysema: Uncommon Association with Common Pathology?

“…In another study, the lungs of copper deficient rats developed emphysematous changes through defective cross linking between elastin and collagen due to decreased lysyl oxidase activity [15]. These findings indicate that dysfunctional elastin makes lung prone for emphysematous changes when exposed to injury/stress, with Wan et al [16] reporting on at least one lifelong nonsmoking adult patient with WBS who had moderate emphysematous changes on CT scan. They went on to perform spirometry on a small subset of young patients with WBS; although they did not demonstrate significant respiratory impairment they postulated that there was an anecdotally higher incidence of respiratory symptoms such as coughing and wheeze, perhaps due to subclinical emphysema and lung disease which may become more apparent at an older age.…”