Fortschritt in der Pathogenese des Marfan-Syndroms und verwandter Krankheiten

Heritable connective tissue disorders comprise a heterogeneous group of disorders that result from genetic defects affecting normal extracellular matrix assembly. Many of these diseases are associated with a significant cardiovascular risk leading to morbidity and mortality in childhood or young adulthood. Prime examples that represent important genetic models for cardiovascular pathology are the Marfan syndrome and related disorders. In these conditions, progressive dilatation of the aortic root leads to aortic dissection, often associated with precocious death. Over the last decade tremendous progress in clinical and molecular research has changed the prevailing concept of these syndromes as structural disorders of the connective tissue into diseases manifesting perturbed cytokine signaling with widespread developmental abnormalities. These insights opened new and unexpected targets for causally directed drug treatments for these aneurysm syndromes, and by extent, also for the more common non-syndromic forms of aneurysm formation, a major cause of morbidity and mortality in the Western world.