Loeys–Dietz Syndrome in the Heterogeneous Cohort of Genetic Aortopathies—Same but Different

Background: The term genetic aortopathy (GA) encompasses a variety of disorders. The best-known associated disease is Marfan syndrome (MFS). Due to constantly evolving research in human genetics, more and more genetic mutations and diseases related to MFS have been found. One of these diseases is Loeys–Dietz syndrome (LDS). Both MFS and LDS belong to the connective tissue diseases. The rarity of these diseases makes it difficult to describe the characteristics but more importantly their differences. Despite the strong overlap and clinically very similar phenotypes, there are crucial differences between them.

Methods: Since 2008, we have studied 847 patients with suspected GA. We detected FBN1 mutation in 189 patients and genetically confirmed LDS in 22 patients. We retrospectively analyzed the type of mutation, prevalence of symptoms and systematically compared the two syndromes.

Results: Out of 304 patients, a mutation could be genetically detected in 231 patients. In total we have a patient population with 189 MFS patients, 22 LDS and 20 patients with other mutations. The initial age of presentation is on average slightly younger in MFS patients (7.9 years) while LDS patients present for the first time at the age of 9.3 years. This could be due to the fact that in our patient group 22% of MFS patients initially present at a young age due to lens luxation, which we have not seen in any LDS patient so far (p < 0.05). However, 61% of LDS patients already had SV dilatation at initial presentation, compared with only 32% in children with MFS (p < 0.01). There are also significant differences in the prevalence of valve vitiation such as mitral valve prolapse (LDS: 48%; MFS: 71%; p < 0.05). In both clinical conditions, we used angiotensin receptor blockers (ARB) as the medication of choice during the course of therapy. They are used with similar frequency in both LDS (45%) and MFS (54%). In both diseases, ARBs provide a significant decrease in SV dilatation (p < 0.05).

Conclusion: Besides the classic MFS, there are many other syndromes in the group of GA. Despite all similarities, there are differences. In our large pediatric patient group with LDS patients we could show that there are, especially at the initial presentation, important differences which help in diagnosis and influence the further disease management.

Publication History

Article published online:
13 February 2024