Ascending Aortic Aneurysms and Dissections: Histopathology and Genetic Testing
CD Tan, ER Rodriguez. Cleveland Clinic, Cleveland, OH
Background: Ascending aortic aneurysms and/or dissections occurring at a young age are often associated with inheritable connective tissue disorders. Genetic testing for mutations in fibrillin (FBN1), transforming growth factor beta receptors I (TGFBR1) and II (TGFBR2) is clinically available for the diagnosis of connective tissue disorders. Marfan syndrome (MFS) is caused by mutations in FBN1 and TGFBR2, while Loeys-Dietz syndrome (LDS) is due to mutations in TGFBR1 or 2.
Design: A total of 223 ascending aortic resections from patients aged 60 or less were accessioned between April 2007 to Aug 2008 and their histopathology results were tabulated. Referral pattern to clinical geneticists and results of genetic testing were reviewed from the medical records in this cohort of patients.
Results: Histopathologic examination showed aortic dissection in 52 patients (23%), cystic medial degeneration (CMD) in 45 (20%), increase in mucopolysaccharide content of the media without elastic fragmentation in 85 (38%), normal aorta in 15 (7%) and atherosclerosis in only 26 (12%). Of these 223 patients, 24 (11%) patients with either aortic dissection or CMD were referred to clinical genetics for evaluation. Five patients met the clinical criteria for MFS and diagnosis confirmed with mutations in FBN1. Nineteen patients did not meet criteria for MFS or LDS and were tested for TGFBR1 and 2; in addition, 4 patients also had FBN1 testing. One patient each were found to have mutation in TGFBR1, TGFBR2 and FBN1. The common clinical findings in these 3 patients are dilation of the ascending aorta, high-arched palate and translucent velvety skin. The patient with TGFBR1 mutation (c.1136T>C) is a 40 year old female with aortic dilatation and CMD on histology. The second patient with TGFBR2 mutation (c.914T>A) had thoracoabdominal aortic dissection at age 52 and found to have an enlarged aortic root. There was moderate increase of mucopolysaccharide material in the aorta but not CMD. Likewise, the 43 year old female with FBN1 mutation (c.2714G>A) did not show CMD in the aortic specimen. Conversely, 16 patients with mild to severe CMD did not have mutations in TGFBR genes.
Conclusions: In this retrospective analysis of patients with ascending aortic aneurysm or dissection, mutations were found in 15% of patients evaluated by a clinical geneticist. Phenotypic expression overlaps in patients with FBN1, TGFBR1 and 2 mutations. CMD is a nonspecific finding in ascending aortic aneurysms and dissections and is not always present in those with inheritable connective tissue disorders.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 51, Tuesday Afternoon