Van der Linde and colleagues previously reported a new “aneurysm-osteoarthritis syndrome” [1van de Laar I.M. Oldenburg R.A. Pals G. et al.Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis.Nat Genet. 2011; 43: 121-126Crossref PubMed Scopus (492) Google Scholar, 2Van der Linde D, Van de Laar IMBH, Bertoli-Avella AM, et al. Aggressive cardiovascular phenotype of aneurysms-osteoarthritis syndrome caused by pathogenic SMAD3 variants. J Am Coll Cardiol;60:397–403.Google Scholar, 3van de Laar I.M. van der Linde D. Oei E.H. et al.Phenotypic spectrum of the SMAD3-related aneurysms-osteoarthritis syndrome.J Med Genet. 2012; 49: 47-57Crossref PubMed Scopus (192) Google Scholar]. Their data showed that this new syndrome is inherited in an autosomal dominant pattern and is manifest in widespread arterial aneurysms and aortic tortuosity. Their previous work demonstrated a pathophysiology for this disease linked to increased transforming growth factor (TGF)-β signaling in the aortic wall. The syndrome is further characterized by early-onset osteoarthritis. The authors' identification of this new clinical entity represents an advance in our overall understanding of aneurysm disease. In their current article [4van der Linde D. Bekkers J.A. Mattace-Raso F.U.S. et al.Progression rate and early surgical experience in the new aggressive aneurysms-osteoarthritis syndrome.Ann Thorac Surg. 2013; 95: 563-569Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar], the authors report the clinical follow-up and surgical outcomes in patients with this disease, including nine valve-sparing aortic root replacements. There was no perioperative or postoperative morbidity or mortality. The aortic tissues did not present any undue level of fragility and were amenable to surgical manipulations. As might be expected in an early clinical report of an uncommon entity, there are shortcomings in the current study. The number of patients is small, and the follow-up interval is short. Specifically, the growth rate assessments—which show aggressive and unpredictably rapid growth in some patients—must be taken with a grain of salt. Differences of only 1 or 2 millimeters in aortic size are nearly impossible to measure, even with modern advanced imaging modalities. The growth rate they calculate (2.5 mm/y) is more than double that in the general population of ascending aneurysms [5Elefteriades J.A. Natural history of thoracic aortic aneurysms: indications for surgery, and surgical versus nonsurgical risks.Ann Thorac Surg. 2002; 74: S1877-S1880Abstract Full Text Full Text PDF PubMed Scopus (592) Google Scholar]. The authors found a growth rate of 20.9 mm/y in 1 patient, thus skewing the data severely. The data on changes in carotid distensibility are similarly impaired by the small number of patients and limited follow-up interval. The recommendation for early intervention is preliminary, based on “fast and unpredictable” growth in some patients. This appears a reasonable recommendation at present, but it must be corroborated as additional experience accrues. The authors suggest that the aortic behavior of these patients is similar to that of Loeys-Dietz syndrome. Indeed, the observation of other shared stigmata with Loeys-Dietz (hypertelorism [widely spaced eyes], bifid uvula, scoliosis, abnormal skin texture) makes aneurysms-osteoarthritis syndrome very reminiscent of Loeys-Dietz. Reminescent also are the dominant genetic transmission and the involvement of (TGF)-β pathways in the pathogenesis. One wonders just how clinically distinct aneurysm-osteoarthritis Syndrome is from Loeys-Dietz. We congratulate the authors for the recognition of their new syndromic manifestation of aortic disease. We appreciate their calling this “aneurysm-osteoarthritis syndrome” to the attention of the surgical audience, and their making some pertinent, but very preliminary, clinical observations and corresponding surgical recommendations. Progression Rate and Early Surgical Experience in the New Aggressive Aneurysms-Osteoarthritis SyndromeThe Annals of Thoracic SurgeryVol. 95Issue 2PreviewAneurysms-osteoarthritis syndrome (AOS), caused by SMAD3 mutations, is a recently described autosomal dominant condition characterized by aneurysms throughout the arterial tree in combination with osteoarthritis. The objective of the present study was to evaluate progression rate of aortic dilation and surgical outcome in AOS patients. Full-Text PDF