The phenotypic spectrum of the SMAD3-related Aneurysms-Osteoarthritis Syndrome (AOS)

Arterial aneurysms are associated with a high morbidity and mortality. Some arterial aneurysms are inherited and due to mutations in different genes in the TGFB signal transduction pathway. We recently identified a new genetic syndrome with arterial aneurysms associated with early-onset osteoarthritis (Aneurysms-Osteoarthritis Syndrome). This new syndrome is caused by mutations in the SMAD3 gene, a gene in the TGFB pathway. In the present study, we describe 8 families with Aneurysms-Osteoarthritis Syndrome caused by different SMAD3 mutations. In the majority of patients early-onset joint abnormalities including osteoarthritis were the initial symptom to seek medical advice. Cardiovascular abnormalities were present in almost 90% of patients, and involved mainly aortic aneurysms and dissections. (By Ingrid van de Laar, MD, http://jmg.bmj.com/content/49/1/47 )