Clinical Symptoms in Children with Genetic Aortopathies—A Monocentric Analysis with over 25 Years of Experience

Background: Genetic aortopathy (GA) is a rare form of cardiovascular disease in childhood. Over the last decade continuously more genetic mutations presenting as GA have been found. The rarity of each disease makes it difficult to systematically describe the characteristics of these diseases. Here we present the clinical data we have collected over the past 25 years from children with all forms of GA. From classic Marfan syndrome (MFS) to Ehlers–Danlos syndrome (EDS) to Loeys–Dietz syndrome (LDS). Through our years of experience, we have one of the largest patient populations for these rare diseases.

Methods: Since 1998 we investigated 846 patients in 3020 visits with suspected GA of which 304 patients were diagnosed clinically or genetically. We retrospectively analyzed the type of mutation, prevalence and age of onset of symptoms from birth to transition into adult medical care.

Results: Out of 304 patients, a mutation could be genetically detected in 231 patients. In total we have a patient population with 189 MFS, 4 EDS, 22 LDS patients and 16 with other mutations. The mutations occur between 0.3% (BGN) and 62.2% (FBN1). Mutation in the FBN1 gene were by far the most frequent. In 17.1% (n = 52) despite clinical diagnosis no genetic variant was found. Especially in pediatric patients, diagnosis based on the Revised Ghent Criteria (RGC) alone is difficult. In our cohort only 23% of patients had a systemic manifestation at first clinical presentation at an average age of 7.9 years. Yet, at the time of transition, 43% had a systemic manifestation. Each clinical symptoms present itself age dependent. For example, Sinus Valsalva (SV) dilatation is present in 51% of cases at the age of 11.3 years. At the time of transition 72% patients show an aortic root dilatation. On the other hand the symptom pneumothorax, with a prevalence of 3.7% (n = 7) in our cohort, does not come close to these marks over the entire follow-up period.

Conclusion: In our large, monocentric pediatric patient group with GA, MFS (FBN1) remains the most frequent form of GA. Each of the typical symptoms presents itself age dependent and must be known to correctly diagnose and treat patients. Some typical symptoms of adult GA patients hardly exist in childhood. Because of these data, we call for the development of a separate clinical score for children with GA to take more account of strict age dependency and to allow earlier clinical diagnosis.

Publication History

Article published online:
13 February 2024