Marfan syndrome in adults: re-investigations in a Norwegian cohort after 10 years

Abstract

Marfan syndrome (MFS) is a heritable connective tissue disorder (HCTD), caused by mutations in the fibrillin-1 gene, FBN1. The syndrome can affect many organ systems, and is difficult to diagnose, due to overlapping features with other HCTD. The phenotype and the severity of the manifestations vary in individuals with MFS, even in individuals with identical mutation and within the same family. Life expectancy has been reduced in MFS patients, mainly due to cardiovascular causes, especially aortic complications. Better diagnosis and treatment seem to improve life expectancy, but prior to this study, no data has documented how much life expectancy has increased, and MFS is still a potentially life-threatening syndrome. Changes over time in the reported manifestations of MFS, are not fully understood. The natural and the clinical history of the manifestations included in the diagnostic criteria, has not previously been described in the same MFS cohort. Furthermore, we need to know the factors influencing the changes in the different organ systems. As life expectancy increases, other aspects of living with MFS, such as health-related quality of life (HRQoL), become more important. The main aims of this study were to reassess the diagnosis of MFS, and after 10 years, describe the changes of all the manifestations in the Ghent criteria in the same Norwegian adult MFS cohort, and to explore survival and causes of death. We wanted to study the changes in HRQoL and assess if organ manifestations can predict these changes. The results from this study show that diagnosis is still difficult and dependent on the results of DNA sequencing, and that new and severe organ manifestations may occur in adulthood and progress throughout life. Despite better diagnosis and better treatment, life expectancy is still reduced in this MFS cohort compared to the general Norwegian population. Physical HRQoL is significantly reduced after 10 years, while mental HRQoL is unchanged. New organ pathology found at 10-year follow-up, did not predict the changes in HRQoL.