Causes of Mortality in the Marfan Syndrome(from a Nationwide Register Study)

Area of Science:

• Genetics and Heritable Diseases
• Cardiovascular Medicine
• Public Health and Epidemiology

Background:

• Marfan syndrome (MFS) is a genetic disorder with a high association with aortic disease, leading to significant morbidity and mortality.
• Previous studies indicate increased risks of aortic dissection, surgery, and sudden death in MFS patients.

Purpose of the Study:

• To evaluate the overall mortality and causes of death in a nationwide Danish population diagnosed with Marfan syndrome (MFS) according to the Ghent II criteria.
• To compare the lifespan and mortality hazard ratios of MFS patients against a matched control cohort.

Main Methods:

• A nationwide register-based study identified 412 Danish MFS patients diagnosed by Ghent II criteria.
• A gender and age-matched control cohort of 41,000 individuals was established.
• Cox regression analysis was applied, adjusting for age and calendar time, with cases and controls stratified.

Main Results:

• MFS patients experienced a significantly reduced lifespan (50 years) compared to controls (60 years).
• The overall mortality hazard ratio for MFS patients was 3.6 (men: 4.0, women: 3.2) compared to controls.
• Aortic disease was the primary driver of increased mortality (hazard ratio 194.6), with unexplained respiratory mortality also noted.

Conclusions:

• Marfan syndrome is associated with a substantially increased mortality risk, predominantly driven by aortic complications.
• While aortic disease is the main cause, unexplained respiratory mortality warrants further investigation.
• Excluding cardiovascular and respiratory causes, MFS did not show increased mortality from other reasons.