A Case Based Approach to Clinical Genetics of Thoracic Aortic Aneurysm/Dissection

Abstract

Thoracic aortic aneurysm/dissection (TAAD) is a potential lethal condition with a rising incidence. This condition may occur sporadically; nevertheless, it displays familial clustering in >20% of the cases. Family history confers a six- to twentyfold increased risk of TAAD and has to be considered in the identification and evaluation of patients needing an adequate clinical follow-up. Familial TAAD recognizes a number of potential etiologies with a significant genetic heterogeneity, in either syndromic or nonsyndromic forms of the manifestation. The clinical impact and the management of patients with TAAD differ according to the syndromic and nonsyndromic forms of the manifestation. The clinical management of TAAD patients varies, depending on the different forms. Starting from the description of patient history, in this paper, we summarized the state of the art concerning assessment of clinical/genetic profile and therapeutic management of TAAD patients.

Figure 1

(a) Parasternal long-axis view of the aortic root and of proximal ascending aorta of our patient, at end-diastole. (b) 95% confidence limits for aortic root diameter at the sinuses of Valsalva in relation to body surface area in adults younger than 40 years (modified from Roman et al. 1989 [1]). In the box, based on the nomogram, predicted size of the aortic root is calculated (3.53 cm) and compared with measured aortic size (5.0 cm) to calculate the Z-score and the aortic ratio.

Figure 2

Magnetic resonance SSFP-based imaging: (a) a diastolic sinus plane image, showing 3 aortic cusps; (b) SSFP sagittal oblique of the ascending aorta's aortic arch and proximal descending aorta. Reported measurements were all performed by orthogonal views at end-diastole.

Figure 3

Chromatogram details of the forward and reverse sequencing of FBN1 gene exon 15 and flanking intronic regions. The sequence (a) shows a pathogenetic missense mutation (c.1906 A>G, p. Arg636Gly) as evaluated by SIFT in silico prediction (b).