Clinical Symptoms in Children with Genetic Aortopathy with or without Genetic Pathology from Birth to Transition: A Monocentric Analysis Over More than one Decade

Background: Genetic aortopathy (GA) is a rare form of cardiovascular disease in childhood. Historically, mainly Marfan's syndrome as the most frequent form of GA was described. Over the last years, continuously more genetic mutations presenting as GA have been found and broadened the spectrum of disease. The rarity of each disease makes it difficult to systematically describe the genetic and phenotypic characteristics of these diseases in childhood. Here, we describe clinical data from children with all forms of GA collected over the past 13 years in our extensive database.

Method: Since 2008, we investigated 681 patients in 1,755 visits with suspected GA of which 243 patients were diagnosed clinically or genetically. We retrospectively analyzed the type of mutation, prevalence, and age of onset of cardiovascular symptoms and systemic manifestations of the Ghent criteria from birth to adulthood.

Results: A total of 62% children with diagnosed GA had an FBN1 Mutation. Each of the other mutations (FBN2, TGFB1/2, TGFBR1/2, and BGN) occurred in between 1 and 5%. In 18%, no genetic variant was found. All clinical symptoms present age dependently. For example, sinus of the Valsalva dilatation and dural ectasia are present in 50% of cases at the age of 15.9 and 16.8 years, whereas pneumothorax does not reach this mark. At the time of transition to adulthood 15.6, 11.1, and 2.5% of patients show these symptoms. In patients with clinical signs of GA but without a genetically proven gene mutation, the prevalence of SV dilatation and mitral valve regurgitation is less frequent than in those patients with a proven genetic variant (33.3 vs. 51.6%, p < 0.05 and 41.2 vs. 67.7%, p < 0.001).

Conclusion: In our large, monocentric pediatric patient group with GA, the classical Marfan syndrome (FBN1) remains the most frequent form of GA. Each of the other types of GA present very rarely. In this cohort, in 18% of patients, no genetic variant could be found, probably representing historical data. With modern genetic next-generation sequencing panels, the diagnostic yield will probably be higher. Each of the typical symptoms of GA present in an age-dependent manner that needs to be known to correctly diagnose and manage patients. Typical symptoms of adult GA patients, for example, pneumothorax, hardly exist in childhood. In patients with clinical but without genetically proven GA some of the cardiovascular symptoms occur significantly less often, making it questionable whether a “clinical” diagnosis of GA is still contemporary.

Publication History

Article published online:
12 February 2022