A Dangerous Bond: Family Making Medical History

MILWAUKEE _ As she stood on the stage in her long black gown, flawless notes flowed from Ame Ewert’s alto saxophone.

Seated in the hall were nearly 300 people, including two dozen relatives and her proud father, Paul, who videotaped Ame’s recital.

One minute and 29 seconds into the performance, the music stopped. Ame fell to the floor, her heart quivering in a life-threatening arrhythmia.

A stunned hush filled the hall.

In the confusion, a doctor in the audience and others made it to the stage and began CPR. Paramedics arrived. Ame’s heart, which had stopped for several minutes, was shocked back to life.

Over the next three months, more jolts would be delivered as the Ewerts learned of a terrible secret that had been lurking in their genes for years, perhaps generations.

Ame, 23; her father, 44; her sister Emily, 21; her brother Alex, 12; and her sister Anna, 4, will go through life knowing that at any moment their hearts could switch into an abnormal beat and cardiac arrest.

Doctors say they never have encountered an inherited abnormality like this. They don’t have a name for it, nor are they entirely sure what causes it.

One thing they are fairly certain of is that the case will make medical history.

“I’ve never seen a family like this,” said Michael Earing, a pediatric cardiologist at Children’s Hospital of Wisconsin and an assistant professor at the Medical College of Wisconsin. “Our goal is to try to unlock genetically what they have.”

That latent affliction hidden within the family’s DNA announced itself on the afternoon of Dec. 10. For her senior recital at Wisconsin Lutheran College, Ame had picked “Concerto in E flat for Alto Saxophone” by Russian composer Alexander Glazunov.

Doctors say stressful situations can trigger irregular heartbeats in some people. And if the stress of the concert and playing before hundreds of people weren’t enough, at the start of the piece there were two miscues between Ame and the pianist.

Her performance was to last about five minutes.

“I didn’t get very far,” said Ame, who has little recollection of what happened.

Family members, including her mother, Karen, and two uncles rushed to the stage.

At first, people thought Ame had fainted or had a seizure, but she continued to lay motionless, turning blue.

“I touched her chest and said, ‘It’s not beating,’” Karen said.

A few minutes after CPR was started, firefighters arrived. Ame’s heart was shocked at least twice before she was transported to Froedtert Memorial Lutheran Hospital just a few blocks away.

It would be eight days before she regained consciousness, 22 days before she left the cardiac intensive care unit and 42 days before she was discharged from the hospital.

Today, she is back at the family’s home. She can talk, feed herself, walk and play her saxophone, but some neurological deficits linger.

“I’m confused a lot,” she said.

Her personality also has changed.

“She doesn’t mask her feelings anymore,” said younger sister Emily. “She’ll tell you if she is mad at you.”

Ame still hopes to someday become a band director.

“I just want to live in my own apartment with friends like I used to do,” she said. “I want to get married.”

When Ame was released from the hospital in January, a medical mystery remained: What had caused her heart to stop?

In the ensuing months, doctors at Froedtert and Children’s Hospital began running a series of cardiac, electrophysiological and other medical tests on Ame and others in her family.

One by one, doctors found that they could easily induce potentially fatal arrhythmias in Ame, Paul and Emily by inserting wires into a vein up to their heart and electrically stimulating the organ.

All three now have cardiac defibrillators implanted in their chests, which shock the heart back into a normal rhythm when it starts beating irregularly.

Eventually, the two younger children also will have to be implanted with the devices.

Arrhythmias can run in families, but specialists in the field say they can’t recall a situation like the one afflicting the Ewert family.

“There are many genetic causes (of arrhythmias), but this is extremely rare,” said Mel Scheinman, a professor of medicine and noted specialist in electrophysiology at the University of California, San Francisco. “I’ve never seen it.”

What makes the Ewerts so unusual are the physical traits that seem to be associated with the arrhythmias.

Other than Ame’s mother, Karen, everyone in the family has a cluster of inherited physical characteristics, known as MASS syndrome or MASS phenotype.

The syndrome is related to Marfan syndrome, a somewhat better-known condition that has affected such noted figures as Abraham Lincoln; Charles de Gaulle; Akhenaten, father of King Tut; and sad-eyed actor Vincent Schiavelli, who died in December of lung cancer. About 200,000 people in the United States have Marfan syndrome and related conditions such as the lesser-understood MASS.

Marfan usually is inherited. Oddly, about 25 percent of those who are diagnosed are the first in their family to learn they have the condition.

Like Marfan, MASS involves a connective tissue disorder. People with MASS also have related skin and skeletal abnormalities such as long limbs and faces and highly flexible joints. The Ewert children, for instance, can bend their thumbs back to their forearms. They also have long arms.

Photos of Paul’s relatives dating back to the late 1800s show people with long-faced, Lincolnesque features.

But having MASS syndrome is not known to be a major risk factor for sudden cardiac death.

In the general population, sudden cardiac death occurs at an annual rate of 0.01 percent. For people with MASS and Marfan syndromes, the rate is 0.02 percent.

People with MASS syndrome also tend to have a normally benign and fairly common structural abnormality of the heart. The condition, known as mitral valve prolapse, has been found in all the Ewert family members, again with the exception of Karen.

The mitral valve is made of two flaps of tissue that open and close between the two chambers on the left side of the heart. When the flaps don’t operate properly, a small amount of blood can move back into the upper chamber.

Mitral valve prolapse is one of the most common heart defects, affecting up to 20 percent of the population. Normally, it is a condition without symptoms. And most of the time it is an isolated condition that is not associated with abnormalities in connective tissue throughout the body.

In some patients, the leakage can get worse over time, putting them at higher risk for arrhythmias, but the Ewerts have only minimal leakage.

The situation is so unusual and perplexing that doctors here plan to publish the family’s case in a medical journal.

“The only thing I know is I don’t know anything,” said Hakan Paydak, an arrhythmia specialist at Froedtert and the Medical College. “This is an amazing case.”

Spared the life-threatening heart defect that plagues her family, Karen Ewert bears a different burden _ being the wife and mother to five medically fragile loved ones.

Like a round-the-clock sentinel, she watches over her family. She checks on them at night. She drives them to events and doctor visits. On a good night, Karen, 43, gets three hours of sleep.

“She’s always got one eye open,” said husband Paul. “She’s a taxi and an advocate.”

She does so much research on the medical condition that some doctors think she is a nurse, Paul said.

She handles the family’s creditors and its mounting unpaid medical bills, already more than $500,000.

“There is no life beyond this situation for me,” she said.

Doctors are especially eager to do genetic testing on the family, a complicated and time-consuming undertaking they hope will culminate in the discovery of a gene mutation associated with the defect.

“These are the kinds of families that can help the world,” said Christine Seidman, a professor of cardiovascular medicine and genetics at Harvard University.

Finding new genetic mutations can add to science’s understanding of arrhythmias, she said.

The genetic testing of the Ewerts will involve screening large areas of various chromosomes and could take up to a year, Earing said.

“Genetic testing is often like finding a needle in a haystack,” he said.

The testing might find a variation in a known gene or a new gene altogether.

Because Ame was the first case and because it is presumed that the other Ewerts have the same genetic flaw, the initial testing will be done on her, he said.

“Once the mutation is identified, we can then begin to unlock how this mutation causes the disease and symptoms,” Earing said.

That, in turn, could lead to new treatments.

In the meantime, Karen’s vigil has taken on greater urgency.

Last month, 12-year-old Alex was taking a shower and Karen wondered why he was taking so long.

He had collapsed in the shower and had been lying in the tub, probably for a few minutes. He got out of the shower on his own and seemed fine, but the next day, he was admitted to Children’s Hospital for tests.

Doctors weren’t able to induce the same kind of life-threatening arrhythmias that occurred in Ame, Emily and Paul. Nonetheless, because of the family’s medical history, they considered implanting a defibrillator in him on the spot. Partly because of his age, doctors instead implanted a device in his chest that constantly monitors his heart.

Alex has passed out a couple more times since the recorder was implanted.

“The good news is, we don’t see anything life-threatening here,” Earing told family members recently as they crowded into the exam room. “The bad news is, he’s always getting dizzy. We’re really in a gray area. There’s nothing in there that bothers me. But because of the family history, it’s a whole different ball game.

“What I would predict is he’s going to get a defibrillator before this is all done.”

Earing, who also is director of the Marfan syndrome and related connective tissue disorder clinic at Children’s Hospital, decided to put Alex on a heart drug that should help prevent him from passing out.

Passing out has become an Ewert family tradition.

Emily could pass out at the slightest provocation.

“She’d bump her knee and she’d pass out,” Karen said. “She’d hit her funny bone and she’d pass out. If she got startled, it would happen. Her heart would race and she would pass out.”

The episodes would come in clusters of three to four in a month. And then she would go for several months without an incident.

Doctors say the episodes in Emily and Alex might be caused by the less-ominous neurocardiogenic syncope, which is a common type of fainting.

Ame, too, had episodes of passing out, including an incident two years before her cardiac arrest. Karen said that at the time it was thought to be a seizure, but now she believes it was an arrhythmia.

Ame underwent testing at Froedtert, but instead of performing an invasive electrophysiological study, doctors put her on a heart medicine, Karen said.

Karen said she believes that if an electrophysiological study had been performed, her arrhythmia would have been found, and she would have been implanted with a defibrillator that would have prevented her collapse in December.

“It should not have taken Ame having a cardiac arrest,” she said. “That makes me angry.”

However, doctors said Ame got the proper treatment two years ago, given the nature of her case then.

Paydak, one of the physicians who treated her, said testing indicated she had neurocardiogenic syncope.

In addition, electrophysiological studies are invasive procedures with potentially serious risks and there is no guarantee that doing one would have found her arrhythmia problem.

Ame has bounced back dramatically since collapsing on the stage.

While she was unconscious in the hospital, the family was told that she might remain in some type of vegetative state for the rest of her life.

Today, she is moving around, talking and playing her saxophone.

But she can get confused and, at times, it seems as if she is searching for thoughts. She lacks motivation and needs a lot of prompting. Her social skills have regressed since the incident.

“You pretty much have to tell her what to do and when,” Karen said.

On a recent Sunday, Ame was all smiles as she sat listening to classmates perform during a benefit concert for her in the same auditorium where she collapsed four months earlier.

Angela Schmill, a clarinet player who was to have performed after Ame in December, took the stage along with several other musicians as the Ewert family and about 200 others listened.

Schmill said she and Ame had always talked about graduating together and starting careers as music teachers.

“I don’t know how, but I have faith she will someday,” she said.

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