Aggressive Cardiovascular Phenotype of Aneurysms-Osteoarthritis Syndrome Caused by Pathogenic SMAD3 Variants

Abstract

AOS predisposes patients to aggressive and widespread cardiovascular disease and is associated with high mortality. Dissections can occur at relatively mildly increased aortic diameters; therefore, early elective repair of the ascending aorta should be considered. Moreover, cerebrovascular abnormalities were encountered in most patients.

Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome

“…Severe dural ectasia, including meningoceles, are sometimes accompanied by neurological signs, due to pressure on the nerves. In contrast to LDS, cerebrovascular abnormalities do not occur at an increased frequency in MFS (27).…”

“…Consequently, these complications are associated with high mortality rates. Similar to MFS, increased aortic stiffness is observed (27). Dilatation of the aortic root can be associated with aortic regurgitation (12).…”

“…As in MFS, the main cardiovascular feature in LDS is a dilatation of the aortic root at the level of the sinus of Valsalva and is present in the vast majority of patients (27). Similar to MFS, a great variability in aortic dilatation is observed amongst patients (11).…”

“…In LDS patients, pulmonary valve stenosis could also develop over time (21). Similar to MFS, MVP and mitral valve insufficiency are more frequently observed than in the general population (27,35), but appear to be somewhat less common in LDS compared to MFS (36).…”

“…Dilatation of the aortic root can be associated with aortic regurgitation (12). Besides aneurysms affecting the aortic root, LDS is known for its involvement of aneurysms affecting arterial branches of head, neck, lung, lower extremities, and thoracic and abdominal aorta (21,27,33). Dissection of the coronary artery and the internal iliac and superior mesenteric artery have been described without prior dilatation (21,34).…”