STORY BY

Deborah Mann Lake

 

Marfan Syndrome

The long & short of a killer gene

There are certain physical features that are considered typical markers for Marfan syndrome, a disorder of the connective tissue that can have deadly consequences. Skeletal traits include an arm span greater than height, flexible joints throughout the body and certain facial features such as a long, thin face and deep set eyes. People also tend to be unusually tall.

Maria Martinez, 5-foot-2, is none of that.

But she does have the nearly silent symptom that can kill: a diseased aorta, the major artery leading from the heart that supplies blood to the rest of the body.

Connective tissue holds parts of the body together and helps control how the body grows. Marfan syndrome most often affects the heart, blood vessels, bones, joints and eyes as well as the lungs. According to the National Marfan Foundation, one in 5,000 people have Marfan syndrome. It occurs in men and women of all races and ethnic groups.

Along with the aforementioned skeletal features, others include curvature of the spine (scoliosis), slipping vertebrae, a caved-in or caved-out chest, flat feet, dislocated lens of the eye and aortic aneurysm or dissection. The weakened aorta can dissect or rupture with little warning, which means symptoms must be recognized quickly and the aorta imaged to confirm the diagnosis. Immediate surgery is required to save the patient’s life.

For years Martinez lived with a family mystery that wiped out nearly an entire generation in its prime and then began affecting members of the next two generations one by one. By the time she wound up in the hospital with pain like a knife wedged between her shoulder blades, she knew the family story in intimate detail. After barely surviving that initial shredding of her aorta, she recited her history to Dianna Milewicz, MD, PhD, George H.W. Bush Professor of Cardiology and director of the Division of Medical Genetics at The University of Texas Medical School at Houston (UTHealth).

Through testing and researching three generations of Martinez’ family, Milewicz was able to tell them with certainty that they had Marfan syndrome.

Marfan is caused by a defect in a gene that controls a connective tissue protein. The defect can be inherited, going back generations, or spontaneous, meaning that person is the first in the family to have it.

"When we examined all the first generation, they were all short and it was virtually impossible to tell they have Marfan," Milewicz says. “That means there may be other Hispanic families that don’t know they have Marfan syndrome and therefore are at risk of having an aortic dissection. Aortic disease is not as common as heart attack or stroke, but it causes a lot of preventable, premature deaths.”

Martinez’ family and two other Hispanic families from Mexico became the subject of an article authored by Milewicz’ research team. It was published in the November 2009 issue of the European Journal of Medical Genetics. In Martinez’ family, four of the six children in her father’s generation died from either confirmed or suspected aortic dissections or aneurysms.

It all began, Martinez explains, in September of 1967. She was 17 and was picking grapes with her family in the fields of California. Her father felt a sharp pain in his back and chest and then he began coughing up blood.

He was diagnosed with pneumonia and it wasn’t until two years later that doctors discovered there was something wrong with his heart. He underwent surgery but was never the same—a shadow of his former self, she remembers.

Then in 1971, a younger brother (her uncle) in his 40s arrived in Houston from Mexico for the same surgery. He returned home after being warned to not do anything physical. “He had a farm, an infant son, a wife and his mother to support,” she says. “He had to work.” He was found dead alongside the fence he was trying to mend. 

By 1975 Martinez’ father had died—from a heart attack, they were told. Ten months later a third brother was taken to a local Houston hospital complaining of pain in his back. She remembers seeing people carrying pints and pints of blood past them and finally the doctor came out and told them her uncle’s aorta had ruptured. It was too late.

The fourth member of that generation, an aunt who was 48, died in 1984 and the family was told her aorta had ruptured.

In 1995, Martinez’ son Jesse Estrada went to the doctor for a hernia in his stomach. Unlike his mother, Estrada was very tall for his family—over 6 feet tall—although one of her cousins was also unusually tall. The doctor thought he heard a murmur in the heart. After Martinez recited the family history, the physician performed further tests that revealed that Estrada, then 21, was a ticking time bomb with a deadly aneurysm that required immediate surgery. It took three months for him to finally get an appointment with a surgeon and undergo the life-saving procedure.

Then it was Martinez’ turn. Three years after Estrada underwent surgery, she experienced her dissection. She was not a candidate for surgery because of unstable blood pressure and was instead placed into an induced coma for 48 hours. In all, she was hospitalized for 11 days. When she was able to speak to her physician, Joseph Coselli, MD, chief of the Division of Cardiothoracic Surgery and professor of surgery at Baylor College of Medicine, she told the family’s tragic tale again.

Coselli, who is part of a collaboration researching aortic aneurysms that is funded by the National Institutes of Health and led by Milewicz, called her. Using a dna sample from Maria, Milewicz's group found a mutation in the gene that causes Marfan's syndrome. In 1999, family members from Mexico joined those already in Houston to give DNA samples. Martinez discovered that her daughter Adriana Estrada, another of the handful of “tall” members of the family at 5-foot-11, also carried the gene. She then began yearly scans of her aorta, along with other family members who carry the gene.

“At first I was shocked when I heard I carried the gene. I always felt different because I was so tall and I hated it…I walked hunchback. I was 5-10 when I was 15,” says Estrada, echoing the feelings of many people who have Marfan.

By 2005 when she was 34, Estrada’s aneurysm had grown to the size that required surgery, which was performed by Hazim Safi, MD, professor and chairman of the Department of Cardiothoracic and Vascular Surgery at UTHealth Medical School and chief of Cardiothoracic & Vascular Surgery at the Memorial Hermann Heart & Vascular Institute; and Anthony Estrera, MD, associate professor of cardiovascular and vascular surgery at the medical school and chief of cardiac surgery at Memorial Hermann-Texas Medical Center.

“I credit Dr. Milewicz for taking the extra step to sit down and listen to my family’s story and find out what was happening,” Estrada says. “I appreciate that God put her in our life.”

 

 

 

 

Last Updated: 6-30-2010

 

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