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 paediatric 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 paediatric LDS patients with and mutations.

Methods: We included 32 LDS patients with either (n = 17) or (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. Patients with were more likely to have undergone aortic surgery (47% vs 12%,  = 0.057) and use angiotensin receptor blockers (93% vs 47%,  = 0.015). Aortic scores were significantly larger in the group at the level of the aortic valve annulus ( = 0.007), sinuses of Valsalva ( = 0.001), sinotubular junction ( = 0.001), and ascending aorta ( = 0.054). Patients with 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: Paediatric LDS patients with present with more severe cardiovascular phenotypes than patients with with larger aortic dimensions and increased aortic stiffness. Our findings suggest that genotypes should be taken into consideration in the clinical management of paediatric LDS patients.