Genetic Roots of Rare but Often Fatal Heart Condition in Young Athletes

The stories of young athletes who die suddenly while engaging in athletic activity grace the front of local newspapers on a seemingly regular basis. People often wonder how this could have happened and what was the cause.

Dr. Daniel P. Judge and a team of colleagues have done a study through John Hopkins to try to get some answers to those questions. According to Judge, the condition that causes most cases of sudden death during athletic activity is known as ARVD ((arrhythmogenic right ventricular dysplasia). Judge says the case that brought his program’s attention to the matter was a case in which a father and daughter both died suddenly during athletic activity. The family members wanted to know what the cause was and what was the risk of having the same thing happen to them. In addition to the usual round of cardiac testing (stress tests, EKG, echocardiogram, cardiac MRI and electrical heart monitoring), Judge says his team really sought to have a blood test that could help to identify those who had the greatest risk for ARVD.

What the study found is that mutations in a gene called plakophilin-2 (PKP2) are the most likely culprit of ARVD, which is one of the leading causes of sudden cardiac death among young athletes. ARVD is characterized by a dysfunctional right ventricle, which beats irregularly and weakens the muscle over a period of time because of excess fat and scar tissue buildup. It can trigger a rhythm disturbance in the heart, which causes death, if left untreated.

“We believe we have pinpointed the genetic mutations responsible for the syndrome in many people, and we expect to have a blood test to identify those at greater risk of developing ARVD clinically available within the next couple of months,” said Judge. “Genetic testing is gradually entering clinical practice. Use of such testing appears to be a good way to identify family members of people with this condition who are at greatest risk of sudden death.”

The report, published in the journal, Circulation, is regarded as the first analysis of the genetic mutations associated with ARVD. The study look at blood samples from 58 patients that were previously diagnosed with ARVD and determined that PKP2 mutation from each sample. At least 30 of the study’s participants were involved in competitive sports. They were all part of the Hopkin’s registry of patients in the United States have the condition.

The researchers compared the results from patients with ARVD to those without and looked at the differences between patients who receive preventative therapy and those who do not. Preventative therapy for ARVD includes the implantation of a defibrillator.

What they found in the study is that there are a total of 13 different mutations within PKP2 and 25 patients each had one. Researchers also noted that patients with PKP2 mutations were more likely to develop ARVD earlier than those who did not have the mutations – in some patients, by an entire decade.

Past research done on the condition at Hopkins showed that ARVD strikes those are relatively young and symptoms could begin appearing well before a diagnosis is made – in some cases 15 years before diagnosis.

Judge, who is an assistant professor at The Johns Hopkins University School of Medicine and its Heart Institute, has said that immediate family members of those who have been diagnosed with or died from ARVD should be screened, however, he cautioned that the presence of PKP2 mutations does not mean that the fatal arrhythmia associated with ARVD will occur.

Judge says that this sort of genetic testing should be done with care. “A family history of cardiac disease should prompt close screening for similar cardiac problems. While genetic testing is becoming a part of the clinical evaluation for inherited cardiac diseases, we do not advise it without genetic counseling,” he said. “Any individual with a family history of a genetic form of cardiomyopathy may decide to proceed with clinical genetic testing after proper counseling. “

Researchers and the Heart Rhythm Society have said that ARVD is responsible for about five percent of the 300,000 sudden cardiac deaths that occur in the United States annually.

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