Bicuspid aortic valve syndrome and fibrillinopathies: potential impact on clinical approach

Abstract

Bicuspid aortic valve (BAV) is a common heterogeneous disorder whose natural history is determined by hemodynamic<br />valvular impairment and/or increased prevalence of aortic abnormalities ranging from dilatation to aneurysm and dissection.<br />BAV-related aortopathy is frequently associated with relevant aortic pathologic changes leading to structural alterations,<br />characteristic degenerative lesions and histological changes of the aorta very similar to those identified and described in<br />patients with Marfan syndrome (MFS), an inherited connective tissue disorder associated with mutations in fibrillin 1 (FBN1)<br />gene in more than 90% of patients. Recently, a 4-fold increase in the prevalence of BAV in MFS patients has been reported.<br />Subsequently, pathogenetic FBN1 mutations in patients with BAV and aortic dilatation/aneurysm in whom MFS and other<br />more severe type 1 fibrillinopathies were clinically excluded have been identified. In this review we discuss how this evidence,<br />together with that of the wide heterogeneity in pathogenetic mechanisms of BAV-related aortopathy, may impact the clinical<br />management of BAV.

Mid-term Clinical Outcomes in a Cohort of Asymptomatic or Mildly Symptomatic Korean Patients with Bicuspid Aortic Valve in a Tertiary Referral Hospital

“…For example, in contrast to the Olmsted county study, in which abnormal auscultation was the most common clinical condition (71%) associated with the first clue of initial diagnosis,20) the wide clinical application and availability of routine echocardiography in Korea can reveal different clinical situations associated with the first diagnosis of BAV. On the other hand, focused screening due to family history of BAV or congenital heart disease was conducted only in 3 patients in our cohort, while previous Western studies reported that familial clustering was involved in 20%-30% of isolated BAV cases21) and that the concordance among first-degree relatives of BAV patients was 6.4% 22). Therefore, our results raised the question of whether we provide appropriate patient education for screening of BAV during routine practice at our institution.…”

Intima-media thickness of the descending aorta in patients with bicuspid aortic valve

“…A combination of genetic, flow and environmental factors in the individual patient is probably responsible for AscAA formation [29]. The fact that microanatomy in the descending aorta (AoIMT) did not differ between BAV and TAV does not exclude differences in aortic function, or inherent tissue weakness as the etiology of BAV aortopathy [30].…”

Bicuspid Aortic Valve: Role of Multiple Gene Variants in Influencing the Clinical Phenotype

“…Furthermore, BAV has been described as an isolated trait or associated with other clinical manifestations in syndromic conditions [familial thoracic aortic aneurysm and dissection, Marfan syndrome (MFS), Loeys-Dietz syndrome, Andersen syndrome, Turner syndrome, William Beuren syndrome, Bosley-Salih-Alorainy syndrome, and Athabascan Brainstem Dysgenesis syndrome] [ 5 , 7 , 8 ]. Identification of a syndromic condition in a BAV patient is clinically relevant in order to personalize indication to aortic surgery [ 9 , 10 ].…”

“…Different genes with divergent inheritance pattern have been described to be associated with BAV [ 6 ]. NOTCH1 (9q34.3, OMIM 190198), a transmembrane receptor involved in signaling pathways regulating cell fate and cardiovascular development processes, represents the main gene demonstrated to be associated with BAV in both familial and sporadic forms [ 7 , 11 , 12 ]. Mutations in NOTCH1 signaling genes have been associated with a wide spectrum of congenital heart defects [ 13 ].…”

“…Shortly thereafter, GATA5 (20q13.33, OMIM 611496) has been also demonstrated to be involved in cardiac morphogenesis and aortic valve development [ 14 ] implicated in BAV pathogenesis [ 7 , 15 , 16 ]. The contribution of additional genes, such as AXIN1, EGFR, ENG, NKX2-5, NOS3, PDIA2, TGFBR1, and TGFBR2 , has been also suggested in BAV disease [ 5 , 7 , 13 , 17 ].…”