Lifelong drug therapy the key to coping with Marfan syndrome

Lifelong drug therapy and monitoring are key to coping with Marfan syndrome, an incurable genetic disorder which causes defective connective tissues, says Sunory Dutt

PUBLISHED : Monday, 02 December, 2013, 12:50pm
UPDATED : Monday, 02 December, 2013, 12:50pm

As a teenager, Ar Tim had an operation to fix a recurring condition called pneumothorax, or collapsed lungs. She has also had surgery for scoliosis. Today, the 35-year-old is subjected to regular cardiovascular tests, as well as electrocardiograms, lung function tests, echocardiograms, regular follow-ups and X-rays of her spine, and occasional CT scans.

All this is because Ar Tim has Marfan syndrome. It's a genetic disorder that causes defective connective tissues which hinder the body's normal functioning.

The syndrome's severity typically increases over time. There is,  as yet, no known cure

The incidence of Marfan syndrome in Hong Kong among adults and children is one in 5,000, according to paediatric cardiologist Dr Dora Wong May-ling from the Hong Kong College of Cardiology. Over the years, she has seen an increase in referrals for diagnosis and treatment of Marfan syndrome.

A network of connective tissues holds the body together, providing a framework for growth and development. Because these connective tissues are found throughout the body, Marfan syndrome can affect many body systems, including the skeleton, eyes, heart and blood vessels, nervous system, skin, and lungs. The syndrome is not specific to any race or ethnic background.

It takes a battery of tests to diagnose the syndrome: heart imaging to determine the proper functioning of the aorta, skeletal imaging to check for abnormal curvature of the spine (scoliosis) or a sunken or protruding breastbone, ophthalmic tests to check for lens dislocation, cataracts, detached retina and glaucoma, and genetic testing.

Although a person with Marfan syndrome is born with the disorder, it may not be diagnosed until later in life. Research has found that the child of a person with the syndrome has a 50 per cent chance of inheriting the disease.

Wong recalls the case of a man with aortic complications resulting from Marfan syndrome whose two daughters were also diagnosed with the syndrome.

However, Ar Tim was diagnosed when she was five years old, despite no family history of it. Even so, the disease has not stopped her from living happily.

"I am well aware of the major complications that can arise from the syndrome," she says. "My lung function is weaker than a normal person's due to my pneumothorax operation. I've also had surgery for scoliosis. I avoid strenuous or vigorous exercise. The most important thing is regular drug taking. Other than that, there's no major change in my lifestyle."

Marfan syndrome may present itself in many ways, according to the US National Marfan Foundation website. Some patients are mildly affected and have only a few of these characteristics, while others are severely affected.

Others may have features that fit the characteristics of Marfan patients, but may be fine. Olympic swimmer Michael Phelps' long arms, slender physique and flexibility were thought to be signs that he has the incurable condition. But he says in his autobiography that he is disease-free.

More than half those with the syndrome experience minimal or pronounced dislocation of one or both lenses of the eye, and retinal detachment. Many of them are also are myopic, and develop early glaucoma or cataracts.

Most people with Marfan syndrome also have problems associated with the heart and blood vessels. Because of faulty connective tissue, the wall of the aorta may be weakened and stretched, a process called aortic dilatation. It increases the risk that the aorta will tear or rupture, causing serious heart problems or sometimes sudden death.

Sometimes, defects in heart valves can also cause problems. Valves may leak, creating a heart murmur. Small leaks may not cause any symptoms but shortness of breath, fatigue, and palpitations are possible with larger leaks.

The syndrome's severity typically increases over time. There's no known cure, except for managing its life-threatening complications with either medication or surgery.

Marfan syndrome patients need lifelong monitoring and care. If undetected, the average person's lifespan rarely extends past 40. But with monitoring and treatment, most people can live into old age.

There has been no study on the life expectancy of Marfan syndrome patients in Hong Kong yet, but the median survival age after detection and medication reported by other studies is 70 years. Life expectancy has risen due to treatment advances, early awareness, and intervention.

People with Marfan syndrome usually need an annual echocardiogram to monitor the diameter of the aorta, or CT scans and MRIs. If the aorta's diameter enlarges quickly or reaches a dangerous size of about five centimetres, an operation would be necessary to replace that portion of the aorta with a synthetic tube to prevent a life-threatening rupture.

"Cardiovascular disease, mainly aortic root dilatation with complication of aneurysm formation and/or dissection, accounts for the majority of premature death in patients with Marfan syndrome," says Dr Lun Kin-Shing, honorary clinical associate professor from University of Hong Kong's department of paediatrics and adolescent medicine.

"The early dilation of the aorta can be detected among children," he says, "through an echocardiograph. But it's a rare occurrence before their teenage years." He cites the case of a 15-year-old Marfan patient who was an award-winning member of his school's swimming team.

He and his parents refused a cardiac operation, despite the discovery of a significant aortic root dilatation in his heart. After two years of explanation, they finally agreed to an operation, which was successful.

But not everybody is as lucky. Lun tells of a 12-year-old girl with Marfan syndrome with aortic dissection who successfully had an aortic root replacement.

But after two years, she developed chest pains and a dissection was found above the repaired aortic graft. Further replacement of the damaged aorta was performed, but she died suddenly one week after the operation, and a severe new dissection of the whole thoracic aorta was found.

In most cases, doctors prescribe medications to lower blood pressure to reduce the strain on the weakened walls of the aorta. Ar Tim, for example, is on a daily medication of a beta blocker to regulate her heart rate and blood pressure.

According to Lun, drug therapy using beta blockers is the mainstay of treatment in Marfan syndrome children with aortic root dilatation before surgery. But he says the efficacy of beta blockers to prevent surgery is not yet proven by large scale study.

"Treatment using new drugs such as an angiotensin receptor blocker have been proposed, and we are awaiting the results of large randomised trials," Lun says.

Patients need to understand the rationale of life-long drug therapy even after cardiac surgery and should develop good drug compliance. Follow-up and assessment of the aortic root dimension is important.

Lun advises the avoidance of isometric exercise and competitive sports to prevent the small risk of dissection. But other types of recreational exercises are good for cardiovascular health.

According to US National Institutes of Health, many studies now under way could lead to a better understanding of Marfan syndrome.