Impact of Genotype-Phenotype Interactions on Cardiovascular Function in Paediatric Loeys-Dietz Syndrome

Background The relationship between genotype and phenotypical vascular and cardiac properties in pediatric Loeys-Dietz syndrome (LDS) patients are not well characterized. This study explores the phenotypical differences in aortic properties and cardiac structural and functional parameters between pediatric LDS patients with TGFBR1 and TGFBR2 mutations. Methods We included 32 LDS patients with either TGFBR1 (n=17) or TGFBR2 (n = 15) mutations. Echocardiographic data included aortic dimensions, distensibility, strain, and stiffness at the level of the annulus, sinuses of Valsalva, sinotubular junction, ascending aorta, and descending aorta. Parameters for left ventricular size and function were also recorded. Results Demographics were similar between the groups. TGFBR2 patients were more likely to have undergone aortic surgery (47% vs. 12%, p=0.057) and use angiotensin receptor blockers (93% vs. 47%, p=0.015). Aortic z-scores were significantly larger in the TGFBR2 group at the level of the aortic valve annulus (p = 0.007), sinuses of Valsalva (p = 0.001), sinotubular junction (p = 0.001), and ascending aorta (p = 0.054). TGFBR2 patients also had significantly lower aortic distensibility and strain coupled with higher stiffness index at the level of the annulus, sinotubular junction, and ascending aorta. Parameters for the descending aorta, cardiac morphology, and cardiac function were similar between the groups. Conclusions Pediatric LDS patients with TGFBR2 present with more severe cardiovascular phenotypes than TGFBR1 patients with larger aortic dimensions and increased aortic stiffness. Our findings suggest genotypes should be taken into consideration in the clinical management of pediatric LDS patients.