Three clinical disorders, Supravalvular Aortic Stenosis (SVAS), Autosomal Dominant Cutis Laxa and Williams-Beuren syndrome, have been associated with intragenic mutations or deletion of the elastin gene (ELN). Supravalvular aortic stenosis is an obstructive vascular disorder that occurs in 1 in 20,000 live births and is characterized by narrowing of the aorta or diffuse aortic hypoplasia. Although the severity of supravalvular aortic stenosis is variable, it often requires surgical intervention. A lack of treatment may result in progressive heart failure and can be fatal. Supravalvular aortic stenosis is often associated with stenosis of other vessels, most commonly pulmonary arterial stenosis.
Cutis laxa is a rare connective tissue disorder that is characterized by lax, inelastic and redundant skin that gives an appearance of premature aging. Although any part of the body may be affected, the loose skin appearance is most prominent around the eyes, face, neck, shoulders, and thighs. Skin fragility, easy bruising, and poor wound healing are not associated with cutis laxa. The autosomal dominant inherited form of cutis laxa due to mutations in the elastin gene (ELN) typically involves the skin but severe congenital pulmonary manifestations and thoracic aortic aneurysm have been observed in individuals with particular ELN deletions.
Williams-Beuren syndrome is a microdeletion syndrome associated with dysmorphic facial features, endocrine and cardiac abnormalities, and cognitive deficits. Severely affected individuals usually have short stature, mental disability, supravalvular aortic stenosis, hypercalcemia, elfin facies, and a distinctive personality often described as “cocktail party” personality. Williams-Beuren Syndrome occurs in 1 in 20,000 to 50,000 live births. The cardiovascular aspects of this disorder are attributed to haploinsufficiency for elastin but at least 15 neighboring genes have been implicated in the various other manifestations of this syndrome.