Marfan syndrome: When a rogue gene unhinges your heart

Olympic swimmer Michael Phelps in his memoir, Michael Phelps: Beneath the Surface talks about the rumours of him being affected with Marfan Syndrome, a genetic disorder. He admits that he did have some early symptoms of this disorder but rules out any health complications so far. He may have been ambiguous about his health status, but the book definitely started conversations around Marfan Syndrome.

Marfan syndrome is a genetic connective tissue disorder that mainly affects the heart, eyes and skeletal system. Its prevalence ranges from one in 5,000 to one in 10,000. It is a hereditary disease, which affects the fibers that support the bones, muscles, organs and other tissues in our body.

What is the main cause of Marfan syndrome?

It is caused by an abnormality in the connective tissue, which helps hold the body together. Dr Douglas Richter, a cardiologist at Cooper University Health Care in New Jersey says, “There is a mutation in the FBN1 gene that encodes for the glycoprotein fibrillin 1 (essential for formation of elastic fibers in connective tissues). There are hundreds of different mutations in the gene that can lead to different degrees of variations in Marfan syndrome.”

In about one-fourth of people with Marfan syndrome, the condition occurs as the result of a new mutation (spontaneous gene mutation) as is the case with Dr Richter. Dr Richter was diagnosed with the condition at the age of 12 in 1975 and neither of his parents had Marfan syndrome. 

Experts say it primarily affects the cardiovascular system. Dr Siddaramappa J Patil, Consultant – genetics, Narayana Health City, Bengaluru says, “The elastic fiber is an important component of connective tissue. When there is a change in the fibrillin gene, the elasticity of the connective tissue gets affected. The aortic valve gets dilated. The heart valves don’t close properly and get leaky. It highly affects the heart.”

Dr Moinak Banerjee, scientist, Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Kerala, adds that about 90% of people with Marfan syndrome develop changes in their heart and blood vessels. “These include aortic aneurysm, aortic dissection, enlarged heart, arrhythmia and heart valve problems,” he says.

Marfan syndrome diagnosis

Marfan syndrome is diagnosed using the Ghent nosology, which combines clinical and genetic factors. Dr Banerjee, also the president of Indian Society of Human Genetics says, “Sometimes, Marfan syndrome is mild so that only a few characteristic features are noticeable right away. Symptoms become evident as changes in connective tissue happen as the person ages.”

Dr Richter was first diagnosed with ectopia lentis (dislocation of crystalline lens in the eyes), which is associated with Marfan syndrome. He had seven surgeries, between 1985 and 2008, related to Marfan – two in the lungs, two in the eyes, twice to repair hernia and the last one in the heart to fix the mitral valve and repair the aorta.

Prenatal detection of the errant gene is now done to diagnose Marfan Syndrome. “My wife does not have Marfan. So, each one of my children had a 50 percent chance of getting it. They (doctors) knew the particular mutation in my FBN1 gene. So, when we were pregnant with our third (child), my wife went for an amniocentesis (pregnancy test to check for genetic disorders in babies) and they found the mutation,” Dr Richter says.

Living with Marfan syndrome

Dr Patil says, “Before the 1970s, the life expectancy beyond 45 years was very difficult, mostly due to aortic valve complications. Moreover, the risk of surgeries was also high. But now, due to advancement of technology, they can live a normal lifespan, unless they have very severe complications.” He suggests the following tips for people with Marfan syndrome to be mindful of.

• Follow up with specialists and take all prescribed medications, regularly.
• Marathons, contact or competitive sports and extreme sports like scuba diving should be avoided.
• Avoid heavy weight-lifting or intense exercises at the gym.
• Do exercises or activities as advised by the doctors.
• Smoking or alcohol should be avoided.
• Maintain a healthy weight.

Takeaways

• Marfan syndrome is a genetic connective tissue disorder, caused by the mutation in the FBN1 gene.
• It is mostly inherited from a parent with the condition. In 25 per cent of the cases, there is a spontaneous gene mutation that causes the disorder.
• It mainly affects three systems – cardiovascular, eyes and musculoskeletal.
• A person with Marfan syndrome usually has distinguishing physical features. 
• Symptoms become evident as changes in connective tissue happen as the person ages.
• About 90% of people with Marfan syndrome develop changes in their heart and blood vessels, leading to complications like enlarged heart, arrhythmia, and heart valve problems.
• It is recommended that they avoid high intense workouts, sports and maintain a proper lifestyle.