Heart: Marfan syndrome, a genetic disease better detected, better operated

One person in 5,000 - and the result, perhaps, of major arterial problems. Marfan syndrome affects around 13,000 people in France. It is a disease resulting from a mutation in the FBN1 gene located on chromosome 15. It is therefore transmissible to descendants via a mode of transmission called “autosomal dominant”: autosomal, because the mutation is located on a autosomal chromosome, that is to say non-sexual (X or Y). Dominant, because a mutation in one of the two copies of the gene is enough to trigger the disease.

The FBN1 gene encodes a protein called “fibrillin 1.” The latter allows the organization of elastin fibers constituting the extracellular matrix of connective tissue, whose role is to ensure organ support. Connective tissue is present everywhere in the body, and this explains why this disease causes a wide variety of manifestations and can affect the heart, eyes, skeleton or skin.

The clinical signs are not the same in all people, even within the same family. The main danger of Marfan syndrome is that it can damage the aorta, the body's main artery which carries blood from the heart to all parts of the body. Due to the greater elasticity of the tissues in patients, the artery will tend to dilate, which can ultimately cause aortic dissection: a partial tear in the wall of the aorta.

Professor Guillaume Jondeau is a cardiologist at Bichat-Claude-Bernard hospital and coordinator responsible for the Reference Center for Marfan syndrome and related diseases. He gives an optimistic assessment: “Since the 1970s, we have made enormous progress, the leading cause of death is aortic dissection, and the leading cause of dissection is the absence of diagnosis. Today, we detect better, we monitor better, we operate on time. We give beta blockers to patients, we avoid brutal and violent efforts which increase tension and promote dissection. Thanks to this, we have gained a lot of life expectancy. Indeed, in the 1970s, there were still 50% deaths at the age of 40, whereas today patients live as long as the general population.”

There is no treatment for the disease yet, but progress is real. It is possible to properly measure the risk using echocardiography and CT scans. The primary goal is to slow the dilation of the aorta by maintaining normal blood pressure using beta blockers which slow the heart. If the dilation is too severe, surgery may be performed. The principle of all interventions is to replace the initial part of the aorta, which is the most fragile area. This type of operation is carried out approximately once every two weeks at the Marfan Syndrome Reference Center, and Professor Jondeau is pleased with a 100% success rate in the last 35 surgeries.

Research continues to progress on diseases related to Marfan syndrome, and today it is no longer a single gene that is studied, but a panel of 38 genes responsible for genetic diseases of the connective tissue. This more detailed knowledge could help provide better patient care. This is why Professor Jondeau calls on all people with an aortic aneurysm or signs suggestive of Marfan to consult a reference or competence center.